International Journal of Paleopathology 3 (2013) 243256

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International Journal of Paleopathology

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Research Article

Osteological evidence of short-limbed dwarsm in a nineteenth

century Dutch family: Achondroplasia or hypochondroplasia
Andrea L. Waters-Rist , Menno L.P. Hoogland
Laboratory for Human Osteoarchaeology, Faculty of Archaeology, Leiden University, The Netherlands

a r t i c l e i n f o a b s t r a c t

Article history: An opportunity to explore osteological features of a form of disproportionate dwarsm is presented by a
Received 29 April 2013 recent archaeological discovery. Excavation of a predominately nineteenth century Dutch cemetery from
Received in revised form 11 August 2013 the rural, agricultural village of Middenbeemster revealed an older adult female with skeletal changes
Accepted 12 August 2013
consistent with achondroplasia. The most marked features are a rhizomelic pattern of shortened and
thickened upper and lower limbs, frontal bossing and a moderately depressed nasal bridge, small lumbar
Keywords:
neural canals with short pedicles, bowing of the femora and tibiae, and short stature (130.0 5 cm). How-
Dwarsm
ever, some common features of achondroplasia like cranial base reduction and shortened ngers and toes
Skeletal dysplasia
Historic cemetery
are absent. The alternative diagnosis of a more mild form of short-limbed dwarsm, hypochondropla-
Family history sia, is explored and aided by archival identication of the individual and her offspring. Five offspring,
including three perinates, a 10-year-old daughter, and a 21-year-old son, are analysed for evidence of
an inherited skeletal dysplasia. The unique addition of family history to the paleopathological diagnos-
tic process supports a differential outcome of hypochondroplasia. This combination of osteological and
archival data creates a unique opportunity to track the inheritance and manifestation of a rare disease in
a past population.
2013 Elsevier Inc. All rights reserved.

1. Introduction
A recent discovery from the excavation of a predominately nine-
teenth century cemetery, Middenbeemster, in the Netherlands,
provides the opportunity to investigate the features and inheri-
tance of a form of disproportionate dwarsm: achondroplasia or
hypochondroplasia. An older adult female (numbered V0945) pre-
sented with marked rhizomelic shortening of the limbs, with a
reconstructed stature of 130.0 5 cm, and several other cranial and
postcranial abnormalities. Archival records identify her as a 66-
year-old female named Sara R.1 (AD 17971863), who married a
carpenter named Brant O. Records indicate she gave birth to seven
children, two of whom were stillborn, one who died at three-days
of age, one who died at the age of 10-years, one who died at the
age of 21-years, and two who lived into old adulthood. Fertility
in achondroplastic females is usually normal (Allanson and Hall,
1986), although higher rates of infertility, dysmenorrhea and early
menopause have been suggested (Ghumman et al., 2005). If the
pelvis is misshaped or narrow vaginal delivery is difcult, causing
increased morbidity and mortality risks for mother and child (e.g.
Corresponding author at: Faculty of Archaeology, Leiden University, PO Box
9515, 2300 RA, Leiden, The Netherlands. Tel.: +31 071 5271685.
E-mail address: a.l.waters@arch.leidenuniv.nl (A.L. Waters-Rist).
1
Full last names are omitted because of ethical considerations.
Kozma et al., 2011). The ve youngest offspring were buried in the
Middenbeemster cemetery and are analysed. The unique opportu-
nity to examine the known offspring of an individual with a skeletal
dysplasia adds greatly to the diagnostic process.
The objectives of this study are to: (1) present the skeletal fea-
tures of individuals with a purported form of disproportionate
dwarsm in order to improve our knowledge of the range of phe-
notypic changes that may be encountered; (2) present the analysis
of the affected individuals offspring in order to draw attention to
the manifestation of disproportionate dwarsm in subadults (<18
years of age); and (3) engage in a differential diagnosis focussed on
achondroplasia and the comparatively less well-known hypochon-
droplasia, in order to make the most accurate diagnosis.
1.1. Background: achondroplasia and hypochondroplasia
Disproportionate or short-limbed dwarsm accounts for over
three quarters of the approximately 200 types of dwarsm, with
achondroplasia by far the most common form. Achondroplasia
prevalence estimates range from one in 10,000 to one in 40,000,
with some agreement on a universal rate of one in 25,000 (Horton
et al., 2007; Oostra et al., 1998; Stoll et al., 1989). Achondropla-
sia is relatively well-documented from skeletal remains in a range
of past populations (Arcini and Frlund, 1996; Farkas et al., 2001;
Frayer et al., 1988; Gadykowska-Rzeczycka, 1980; Knol et al., 1996;

1879-9817/$ see front matter 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ijpp.2013.08.004
244 A.L. Waters-Rist, M.L.P. Hoogland / International Journal of Paleopathology 3 (2013) 243256

Kozma, 2006; Kozma et al., 2011; Larje, 1985; Polet and Orban,
1996; Sables, 2010; Slon et al., 2011; Snow, 1943), as well as from
material culture depictions (Bernal and Briceno, 2006; Enderle,
1998; Haworth and Chudley, 2001; Rodriguez et al., 2012). Over 99%
of achondroplasia cases are caused by mutations of the broblast
growth factor receptor-3 (FGFR3) gene on chromosome 4 (Rousseau
et al., 1994; Shiang et al., 1994). In normal individuals FGFR3 func-
tions as an inhibitor to the proliferation and terminal differentiation
of growth plate chondrocytes (Deng et al., 1996). In achondroplasia
the mutated receptor is constitutively active and exaggerates the
normal physiological process (Horton et al., 2007) leading to slow
cartilage-to-bone turnover so that bones that grow by endochon-
dral ossication (e.g. the limb bones) become shortened (Horton
et al., 2007). By adulthood, height ranges from 118 to 145 cm for
males and 112 to 136 cm for females (Horton et al., 1978; also see
Hunter et al., 1996). Bones that grow via intramembranous ossi-
cation (e.g. the cranial vault), or endochondral bones with a slow
growth rate, are less affected, explaining why this type of dwarsm
is classied as disproportionate. Fig. 1. Middenbeemster, The Netherlands.
Clinical research has found that 8090% of achondroplasia cases
are de novo, while 1020% of cases are a result of the mutation being
clinicians have discussed the two diseases as a single complex
passed down from an affected parent (Vajo et al., 2000). Achon-
(the hypochondroplasiaachondroplasia complex) (Sommer et al.,
droplasia has an equal chance of occurring in either sex and because
1987). They do, however, result from different FGFR3 mutations
the mutated allele is dominant, an affected parent has a 50% chance
and since the late 1990s are easily distinguished with genetic
of passing it on. The mutation has complete penetrance, meaning
testing. Francomano (2005) notes that general agreement is emerg-
that all individuals will have clinical symptoms. However, there is
ing that the prevalence of hypochondroplasia is similar to that of
variation in the severity of phenotypic change (in part due to the
achondroplasia. Given this, it would be expected that hypochon-
extent of changed FGFR3 signalling) such that major and mild forms
droplasia occurred at a similar rate as achondroplasia in past
of achondroplasia are recognised (Rimoin, 1988).
populations. Yet, to our knowledge hypochondroplasia has never
In addition to achondroplasia, a milder form of short-limbed
been documented in a paleopathology context, in contrast to the
dwarsm, hypochondroplasia, also results from mutation to the
comparatively well-documented achondroplasia. It is important to
FGFR3 receptor (Bellus et al., 1995, 1996). The milder clinical and
recognise hypochondroplasia in past populations to get an accurate
radiographic features of hypochondroplasia include short arms and
understanding of congenital conditions. Moreover, in osteoarchae-
legs, with less overall height reduction, on the order of two to
ology short stature is often attributed to nutritional stress, but other
three standard deviations below the population mean (male stature
causes, such as hypochondroplasia, should be taken into consider-
range of 138165 cm; female stature range of 128152 cm) (Appan
ation.
et al., 1990; Maroteaux and Falzon, 1988; Oberklaid et al., 1979;
Walker et al., 1971). As in achondroplasia, the cranium is nor-
mal to large in size (macrocephaly), often appearing especially 2. Materials
large in comparison to the underdeveloped appendicular skeleton
(Oberklaid et al., 1979; Walker et al., 1971). Hypochondroplasia The Middenbeemster cemetery (Fig. 1) was in use from AD 1612
is often differentiated from achondroplasia by the lack of changes to 1866. According to archival documents most skeletons date to
to the facial skeleton (Francomano, 2005; Langer et al., 1967; the nineteenth century. Approximately 450 individuals were exca-
Wynne-Davies et al., 1981; although see Oberklaid et al., 1979). An vated by Leiden University and the archaeology company Hollandia
important clinical marker of achondroplasia and hypochondropla- Archeologen in 2011. Individual V0945 was interred in a normal-
sia is the failure of caudal increase in the interpedicular distance of sized cofn, and skeletal preservation and completeness are very
lumbar vertebrae 15 because of early fusion of the pedicles to the good. All of the offspring have preservation and completeness that
vertebral bodies at the neurocentral synchondrosis (Appan et al., are good to very good.
1990; Jeong et al., 2006; Srikumaran et al., 2007). Finally, the fol- Middenbeemster was located in the centre of the Beemster
lowing features that are common in achondroplasia may occur in municipality, a rural community of mainly dairy farmers and
hypochondroplasia, but are less likely to be severe or even to form labourers. There are various archival documents for the Midden-
at all: long bone thickening, lower limb bowing, lumbar lordosis, beemster community spanning the seventeenth to nineteenth
and short and broad hands, feet, and os coxae (Oberklaid et al., century. Amongst these is a cemetery ledger that contains the
1979; Walker et al., 1971). Because the features of hypochondropla- name, age-at-death, parents, marriage, and occupation for most of
sia are less pronounced, it is usually diagnosed at a later age, and the individuals interred between AD 1829 and 1866. From the post-
can even go undiagnosed as taller hypochondroplastics merge with Mediaeval period there are also military archives assessing tness
the shorter members of the general population (Francomano, 2005; for most males over the age of 18 years, listing height and major
Oberklaid et al., 1979). Hypochondroplastics have a thick, muscular diseases/anomalies. Table 1 shows the osteological and archival
appearance often described as stocky (Francomano, 2005). information for each of the analysed individuals. We have some
The prevalence of hypochondroplasia is not well known for archival information about individual V0945s parents but not their
several reasons: its more recent recognition as a distinct clini- skeletons.
cal entity; the lack of agreement for a set of diagnostic criteria;
the overlap in phenotype between achondroplasia on the one 2.1. Methods
end and normal or unaffected on the other end, and that no
single morphological or radiological feature is unique to hypochon- Osteological examination was conducted prior to acquiring
droplasia (Almeida et al., 2009; Oberklaid et al., 1979). Some archival information about age, sex and stature. For the adults,
 A.L. Waters-Rist, M.L.P. Hoogland / International Journal of Paleopathology 3 (2013) 243256
Table 1
Osteological and archival data for individuals examined for disproportionate dwarsm from the Middenbeemster cemetery, The Netherlands.
Site ID number Osteological
data
Estimated age-at-death Estimated Stature (Fully
sex method)
V0945 Old adult 50+ years Female 130.0 4.5 cm
V0884 Perinate 39 2 weeks in utero n/a
V0963 Adolescent 17 1 year Male 158.6 2.0 cm
V0716 Juvenile 7.5 2 years n/a
V0486 Perinate 39 4 weeks in utero n/a
V0485 Perinate 40 2 weeks in utero n/a
a
Sara R. married Brant O. (born in 1801) in 1827.
b
Stature data only collected for adult males.
c
Two additional children were born to Sara R. and Brant O.: a daughter named Sara O. who was born in 1830, and a son named Dirk O. who was born in 1832. They were
not buried in the Middenbeemster cemetery because they died after it closed in 1866. Archival records note that Sara O. died in 1907 (at 77 years of age). It is not known
in what year Dirk O. died but he is noted as present the wedding of his son in 1896 making him at least 64 years old. Archived military records list the height of Dirk O. as
152.4 cm. The heights of two of Dirk O.s grown sons (Klaas O. and Brant O.), thus Sara R.s grandsons, are also listed, at 164.7 and 166.8 cm, respectively.
living stature was estimated using the Fully (1956) anatomical
method, revised by Raxter et al. (2006). In the adults, age was
estimated from pubic symphysis morphology (Suchey and Brooks,
1990), auricular surface morphology (Buckberry and Chamberlain,
2002), sternal rib end morphology (Iscan and Loth, 1986), and cra-
nial suture closure (Meindl and Lovejoy, 1985). Sex was estimated
using assessment of sexually dimorphic features as described in
Buikstra and Ubelaker (1994), Phenice (1969), and the Workshop
of European Anthropologists (WEA, 1980).
For the perinates, gestational age was estimated from den-
tal development stage following Demirjian et al. (1973) and
tooth length from Liversidge et al. (1998). The detailed measure-
ments provided by Fazekas and Kosa (1978) and Scheuer and
MacLaughlin-Black (1994) were used to assess whether or not
the crania were large for age. Age from long bone length was
estimated using the measurements of Fazekas and Kosa (1978)
and Maresh (1970) in order to assess if individuals were small
for age. Foetal age from bone development and fusion was esti-
mated based on Humphrey and Scheuer (2006), Scheuer and Black
(2004), and Bagnall et al. (1977). For the juvenile, age was esti-
mated from dental development stage following Moorrees et al.
(1963) and dental eruption from Ubelaker (1989). Age was also
estimated to assess size-for-age from these standards: epiphyseal
fusion from Schaefer et al. (2009), cranium size from Dekaban
(1977) and Young (1957), clavicle length from Black and Scheuer
(1996) and Saunders et al. (1993), scapula size from Rissech and
Black (2007), ilium size from Rissech and Malgosa (2005), and limb
long bone length from Maresh (1970). For the young adult male
many of these metric methods were also applied in order to assess
size-for-age.
The main method of this study is the analysis of the skeletal
remains of the affected individual and her offspring for features
consistent with a form of disproportionate dwarsm. Table 2 lists
the 31 features examined in the adults, compiled from multiple
clinical studies in an effort to incorporate all possibly relevant oste-
ological markers. Because the number of affected features varies at
different ages, 16 were assessed in the perinates, and 26 in the juve-
nile (age range of 712 years). In addition, in the assessment of the
perinates, the radiographic appearance of their proximal femora
was undertaken to see if there were areas of translucency, a feature
sometimes seen in achondroplastic infants (Horton et al., 2007). In
achondroplastic subadults, many metaphyses have a ared appear-
ance, with the distal femur and proximal tibia taking on respective
chevron and circumex shapes (Horton et al., 2007), thus, this was
assessed.
Radiographs were taken at the Leiden University Medical Cen-
tre on a Canon Lanmix CXD1-40C. CT-scans of the right humerus,
245
Archival data
Name Birth year Age-at-death Sex Statureb Relation to
(AD) Sara R.c
Sara R.a 1796 66 years Female
Trijntje O. 1834 3 days Female Daughter
Pieter O. 1835 21 years Male 158.5 cm Son
Hessel O. 1838 10 years Female Daughter
no name given 1839 Stillborn Sex not indicated Offspring
no name given 1840 Stillborn Sex not indicated Offspring
femur, and tibia of individual V0945 were taken at the Academic
Medical Centre in Amsterdam on a Phillips Brilliance CT-scanner.
CT-scans were taken at 35 and 50% bone length. 3D cross-sectional
images were imported into Image J, and analysed using Moment
Macro. Internal and external bone morphology of individual V0945
was compared to a sample of 23 unaffected females from the
Middenbeemster cemetery. The relevant properties are cross-
sectional area (CA) and polar second moment of area (J), which
reconstruct the mechanical loading history of the scanned bones.
CA (i.e. the thickness or thinness of the bones wall) is inu-
enced by the amount of muscular force put on the bone and
lean body mass. J reects a bones torsional rigidity or its resis-
tance to axial compression and tension. The CA of the upper
and lower limbs was standardised by body mass, and J was
standardised by body mass multiplied by the square of bone
length as recommended by Ruff (2008). Body mass was estimated
using a height-to-weight growth curve for modern Dutch achon-
droplastic individuals (Rietman et al., 2008). To our knowledge
body mass growth curves are not available for hypochondropla-
sia (see Appan et al., 1990 for growth data of 84 hypoplastic
subadults).
3. Results: morphological descriptions
3.1. Individual V0945 Sara R. 66-year-old female
Table 2 presents the assessment of features common in dispro-
portionate dwarsm for this individual. Her estimated stature is
130.0 4.5 cm, which is 31.7 cm, or almost 5 standard deviations
below the average adult female height from the Middenbeemster
collection (n = 44, mean stature is 161.8 6.7). In a rhizomelic pat-
tern, the upper segments of the upper and lower limbs are the
most shortened (Fig. 2). Relative to normal adult females from Mid-
denbeemster, proximal limb segments (the humerus and femur)
are shortened by 20 and 28%, respectively. Distal limb segments
(radius, ulna, tibia, bula) are shortened by 1619%. CT scans reveal
thick cortical bone in the mediolateral portions of the diaphyses of
the right humeri, femora and tibiae (set insets in Figs. 3 and 4),
while the anterioposterior portion of the diaphyses are thinned,
likely in part due to osteoporosis. Assuming a normal body weight
for achondroplastics, bone rigidity of the limbs as assessed by J,
indicates higher resistance to bending stress than average Mid-
denbeemster females (Table 3). Many muscle attachment sites
are pronounced, especially on the humeri (Fig. 3; see Table 2 for
specics). Osteoporosis is present as evidenced by mean cortical
areas that are two to three standard deviations below the adult
female mean from Middenbeemster (Table 3). No osteoporotic
246 A.L. Waters-Rist, M.L.P. Hoogland / International Journal of Paleopathology 3 (2013) 243256

Table 2
Osteological features associated with disproportionate dwarsm in individual V0945 (Sara R.).

Features associated with disproportionate dwarsm Presence Notes about appearance

Skull
Macrocephaly No
Frontal or parietal bossing Yes Both frontal and parietal
Depressed nasal bridge (midface hypoplasia) Moderate Less severe than in most other archaeologically documented dwarfs
Contracted skull base (small pars basilaris) with small foramen No Foramen magnum maximum length = 29.8 mm, maximum
magnuma width = 22.3 mm
Oval foramen magnum (versus circular) Yes
Evidence for chronic otitis media (EAM closure; infection of petrous No Most common in infants and children (25 affected; Hunter et al.,
pyramid or mastoid process) 1998).
Dental crowding/malocclusion n/o Edentulous
Prominent/protruding mandible Yes
Appendicular skeleton
Shortened limbs Yes
Thickened cortical bone in limbs Partially Thickened in medial and lateral portions (thin in anterior and
posterior portions, likely in part because of osteoporosis)
Rugose muscle attachment sites Yes
Rhizomelic pattern of shortened limbs (proximal limb segment most Yes
shortened)
Bowed tibia (genu varum) Yes
Fibula relatively long compared to tibia Yes Longer by 0.8 cm
Coxa vara (<120 degree angle between head and shaft of femur) Yes Approximately 110
Trident hands: ngers widely opposed and of equal length No
Short ngers No
Short toes No
Reduced extension/rotation of elbow joint (posterior bowing of Yes
humerus-radius)
Hyperextensibility of knee joint Possibly Non-normal angle resulting in an unstable joint.
Axial skeleton
Short, rectangular ilium No
Acetabular roof horizontal or notched No May not be evident because its appearance lessens with age
Small greater sciatic notches No
Short, wide pubis and ishium No
Short lumbar vertebral pediclesb Yes (in mm) T9 = 11.79, T10 = 11.97, T11 = 10.31, T12 = 9.48, L1 = 12.19,
L2 = 11.15, L3 = 10.28, L4 = 8.99, L5 = 8.69
Lack of increase in interpedicle distance from L1 to L5c Partially (in mm) L1 = 17.94, L2 = 19.01, L3 = 17.55, L4 = 19.10, L5 = 20.64 (no
increase from L2 to L3; L2 and L4 nearly equal)
Thoracolumbar kyphosis No Common in infancy-childhood. Usually resolved by adolescence
Relatively small vertebra neural foramen possibly causing stenosisd Yes Especially narrow in T58 and L45. Sagittal diameter of neural canal
in mm: T2 = 10.90, T3 = 12.26, T4 = 12.80, T5 = 11.04, T6 = 9.30,
T7 = 10.81, T8 = 11.59, T9 = 12.31, T10 = 11.68, T11 = 12.05, T12 = 13.08,
L1 = 12.92, L2 = 11.00, L3 = 10.83, L4 = 9.81, L5 = 10.84.
Deformed odontoid process (projects posteriorly and superiorly) Possibly 5 mm bony projection from superior end along anterior side
Short, attened vertebral bodies No
Relatively short ribs (narrow thorax) with ared sternal ends No
Additional features
- Robust muscle attachments of these muscles: L and R humeral deltoid, teres major, and pectoralis major/latissimus dorsi, L and R os coxae gluteus maximus, medius
and minimus, and L and R muscles attached to the femoral linea aspera (i.e. vastus medialis and lateralis, adductor brevis, longus, and magnus, and short head of the
biceps femoris).
- Extensive and severe osteoarthritis in these joints: L and R glenoid cavities, L and R acromioclavicular, L and R humeral heads, L and R olecranon processes, lumbar
vertebrae articular facets (L1L5), L and R acetabulum, L and R femoral heads, L and R femoral epicondyles and condyles, L and R patellae, L and R tibial condyles, L and R
bulae heads, L and R bulae malleoli.

n/o = not observable.

a
The average adult with achondroplasia has a foramen magnum that is equivalent to that of a newborn in transverse and that of a two-year-old in sagittal diameter (Hecht
and Butler, 1990).
b
Measured from the posterior border of the vertebral body at the level of the upper border of the pedicle to the posterior body of the upper articular facet.
c
Measured as the minimum distance between the medial surfaces of the pedicles.
d
Sagittal diameter of neural canal measured as the shortest midline perpendicular distance from vertebral body to inner surface of neural arch. Jeong et al. (2006) found
stenosis was most common when the upper lumbar neural canals were narrowed.

Table 3
Percentages of cortical area and polar second moment of area in long-bone cross-sections from individual V0945 compared to unaffected females from the Middenbeemster
cemetery (n = 23), The Netherlands.

Limb location Cortical area Polar second moment of area (mm4 )

V0945 Unaffected female mean V0945 V0945 V0945 Unaffected female mean
and SD (n = 23) 1SD mean +1SD and SD (n 23)

Humerus 35% 55.7 75.0 8.0 28.8 23.7 20.8 16.0 3.9
Humerus 50% 47.6 73.5 7.3 36.3 29.9 26.2 18.24 4.0
Femur 35% 58.4 76.4 5.8 121.8 100.1 87.8 34.8 8.1
Femur 50% 52.6 64.9 5.5 100.6 82.8 72.6 26.4 11.5
Tibia 50% 55.1 78.5 4.1 64.6 53.2 46.6 27.1 6.11
 A.L. Waters-Rist, M.L.P. Hoogland / International Journal of Paleopathology 3 (2013) 243256
Fig. 2. Skeleton of individual V0945. Identied as 66-year old female named Sara R.
Note shortened limb long bones.
micro- or macro-fractures were observed. The femora and tibiae
are bowed in a mediolateral plane, causing a genu varum deformity
that affected gait (Fig. 4).
Additional features in this individual that have been noted in
clinical achondroplasia research include a bossed forehead, pari-
etal bossing, a depressed nasal region (although depression is
not severe), an oval shaped foramen magnum, and a protruding
mandible (likely exacerbated by complete antemortem tooth loss
and alveolar resorption) (Fig. 5). In the axial skeleton the neural
canals of lumbar vertebrae 45 and thoracic vertebrae 58 are espe-
cially narrow, which may have been causing spinal stenosis (Fig. 6).
All lumbar vertebrae neural canal sagittal diameters are well below
the mean values of normal adult females (by 8.411.6 mm) as
247
Fig. 3. Left humerus of individual V0945, on the left, compared to humerus of a
normal adult female from Middenbeemster, on the right. Note shortening and robust
muscle attachments. Bottom left inset displays 50% mid-shaft cross-section.
reported by Hinck et al. (1965) (Table 2). The pedicles of tho-
racic vertebra 9 to lumbar vertebra 5 are substantially shortened
in keeping with the ranges reported by Srikumaran et al. (2007) for
achondroplasia [see Kumar et al. (2006) for additional achondropla-
sia vertebrae measurements of a different sample and Urrutia et al.
(2009) for normal range] and there is a lack of increase in the inter-
pedicular distance of lumbar vertebrae 23, with 2 and 4 of almost
equal size (Table 2). Osteoarthritis, a common complication of mal-
formed or lax joints (Jaffe, 1972), was severe in most limb joints and
the cervical and lower thoracic through to lumbar spine (Table 2).
Not all traits that are usually found in achondroplasia are
observed in individual V0945. Lacking are: short and broad hands
with a trident appearance (ngers of roughly equal length) and
shortened pedal phalanges; a large cranial vault; cranial base
reduction resulting in a small foramen magnum; changes in the
os coxae including squared ilia, a narrow greater sciatic notch, and
shortened pubes and/or ishia; attened vertebral bodies; lumbar
lordosis or kyphosis; complete lack of caudad increase in lum-
bar vertebrae interpedicular distance; and nally, shortened ribs
causing a narrow thorax.
3.1.1. Individuals V0884, V0486, V0485 Trijntje O. 3-day-old
female, and two stillborns of unknown gestational age and sex
Table 4 contains the results of the analysis of the three perinates
for evidence of a skeletal dysplasia. None have any pathognomonic
features of achondroplasia or any other skeletal dysplasia. Long
bone lengths of all three perinates are in the range of 3842 weeks
as would be expected in normal full-term newborns and none of
the long bone metaphyses are ared. None of the long bones or
other post-cranial elements are malformed. Bowing of the legs is
not found in achondroplastichypochondroplastic infants because
it is related to bular overgrowth which is absent or slight prior
248 A.L. Waters-Rist, M.L.P. Hoogland / International Journal of Paleopathology 3 (2013) 243256

Table 4
Results of age estimation and pathological marker assessment for the three perinate offspring of disproportionate dwarsm individual V0945 (Sara R.).

Site ID number, Deciduous tooth Deciduous tooth Cranial bone size Long bone size age Primary bone and Pathological markers
name, age and sex formation age length age estimate age estimate estimate epiphyseal union possibly related to skeletal
from archives estimate age estimate dysplasia

V0884, Trijntje O., 1 2 weeks 39 2 weeks 3840 weeks 3840 weeks Perinate Slight swelling of sternal
3-day old, female postnatal prenatal prenatal prenatal end of ribs 69
V0486, no name Less than 40 weeks 36 3 weeks 3640 weeks 3840 weeks Perinate None
given, stillborn of prenatal (birth) prenatal prenatal prenatal
unknown sex
V0485, no name Less than 1 week 3 3 weeks 3840 weeks 2 2 weeks Perinate Crowding of (unerupted)
given, stillborn of postnatal postnatal prenatal postnatal mandibular anterior teeth
unknown sex

disarticulated, a common occurrence in perinates because of open

fontanelles and the lack of suture fusion. Most of the thinner vault
bones are fragmented and warped post-mortem, which prevented
cranial measurements used to assess size and hence detection of
macrocephaly. Measurements were possible on the thicker cra-
nial base elements (i.e. pars petrosa, pars lateralis), and these are
in the normal size range of a full-term foetus for all three peri-
nates. In sum, there is no morphological evidence for a skeletal
dysplasia in any of the three perinates. It is important to note that
because achondroplasia/hypochondroplasia manifests differently
in foetuses and infants than in adults, it is more difcult to detect
in this group. It is consequently impossible to rule out that these
perinates had a skeletal dysplasia.

3.1.2. Individual V0716 Hessel O. 10-year-old female

Fig. 4. Left femur and tibia of individual V0945, on the right, compared to femur and
tibia of a normal adult female from Middenbeemster, on the left. Note shortening
and mediolateral bowing resulting in a genu varum deformity. Upper and lower
right insets display 50% mid-shaft cross-sections.
to the age of one year (Stanley et al., 2002) and is thus consis-
tently absent. Radiographs of the left femora reveal no abnormal
area of increased translucency in the proximal ends (Fig. 7). It was
not possible to measure vertebral pedicle length or interpedicle
distance because neural arches are unfused and the exact position
of each arch could not be determined. All three crania were found
Table 5 contains the age estimations based on dental formation
and eruption, epiphyseal fusion, and bone size for the 10-year-
old daughter. She had somewhat delayed dental formation and
eruption (7.68.5 years), epiphyseal closure that, while slightly
delayed, is generally consistent with her age (810 years), and
limb long bone lengths that are markedly lower than her age (57
years, with a mean of 6 years). The clavicles, while slightly short,
are of a size consistent with her age (810 years). The scapu-
lae are somewhat small for age (7.08.5 years). The breadths of
the ilia are also small (6.97.4 years). None of the long bones or
other post-cranial elements are bowed or malformed. However,
this individual has an extra (13th) thoracic vertebrae and corre-
sponding rib. To the authors knowledge there is no evidence that
this occurs more often in disproportionate skeletal dysplasias. Long
bone metaphyseal ends are not markedly ared, and there are no
chevron or circumex deformities of the distal femoral or proximal
tibiae metaphyses. Lower thoracic and lumbar vertebrae pedicle
lengths are not shortened; however, there was a failure of caudad
increase in interpedicular distance for lumbar vertebrae 12 and
34 (Table 5). The sagittal diameters of the lumbar neural canals
are smaller than the mean reported by Hinck et al. (1965) for 9
and 10-year-old females (by 5.17.7 mm) (Table 5). The cranium is
large, especially bulbous across the sagittal plane, with a breadth
measurement consistent with an individual older than 1920 years.
Cranial length is also large for age, at 1520 years. The cranium is
thus classied as macrocephalic (Fig. 8).
3.1.3. Individual V0963 Pieter O. 21-year-old male
Table 6 contains the age estimations based on dental formation
and eruption, epiphyseal fusion, and bone size for the 21-year-
old son. Dental eruption age is consistent with a 21-year-old, and
epiphyseal closure is within the range of normal inter-individual
variation (18 years). The most marked difference between known
age and estimates comes from the limb long bones, which are the
size of a 12 to 14-year-old. The distal limb segments (radius, tibia,
and bula) are the most stunted a mesomelia pattern (Fig. 9). The
 A.L. Waters-Rist, M.L.P. Hoogland / International Journal of Paleopathology 3 (2013) 243256 249

Table 5
Age range of dental formation and eruption, epiphyseal fusion, and bone size for individual V0716, Hessel O., 10-years of age.

Dental maturation and eruption, epiphyseal fusion Stage Age estimate

Permanent tooth development Tooth 21: R 7.6 0.8 years

Dental eruption Between stage 8 and 9 years 8.5 2 years
Epiphyseal fusion SI neural arch fused (>7 years); ischiopubic ramus unfused (<11 years) 810 years

Cranial measurement Length (cm) Age range Comments

Cranial maximum length 16.8 n/a

Cranial maximum breadth 15.0 >1920 years
Cranial maximum height 12.6 1520 years
Frontal arc 12.5 n/a Standard applies to males only

Post-cranial measurement L (cm) R (cm) Age range Comments

Clavicle length 9.4 9.5 810 years

Scapula length (aka height or anatomical breadth) n/o 9.6 78 years
Scapula width (aka breadth or anatomical length) 6.1 n/o 8.6 years
Supra-scapula height n/o 27.1 7.5 years
Humerus maximum length 19.0 n/o 6 years
Radius maximum length 13.9 n/o 56 years
Ulna maximum length 15.3 n/o 6 years
Iliac breadth 9.3 9.1 6.97.4 years
Iliac length n/o n/o n/o Not fused
Femur maximum length 26.9 27.0 6 years
Tibia length 21.9 21.9 6 years
Fibula maximum length 21.8 22.0 67 years

Metaphyseal aring or chevron-circumex shape Absent

Lumbar vertebra neural canal sagittal diameter (in mm) L1 = 13.07, L2 = 11.50, L3 = 10.03, L4 = 9.52, L5 = 12.02
Lower vertebra pedicle length (in mm) T9 = 15.90, T10 = 12.24, T11 = 11.26, T12 = 11.51, L1 = 11.87, L2 = 11.35, L3 = 11.70, L4 = 10.96, L5 = 9.19
Lumbar vertebra interpedicular distance (in mm) L1 = 19.53, L2 = 19.12, L3 = 19.73, L4 = 19.50, L5 = 22.52 (Size should increase from L1 to L5)

n/a = not applicable; n/o = not observable.

Fig. 5. Skull of individual V0945. Top left = front; bottom left = side; top right = superior; bottom right = inferior. Note frontal bossing, parietal bossing, moderately depressed
nasal region, oval foramen magnum, and protruding mandible.
250 A.L. Waters-Rist, M.L.P. Hoogland / International Journal of Paleopathology 3 (2013) 243256

Table 6
Age range of dental formation and eruption, epiphyseal fusion, and bone size for individual V0963, Pieter O., 21-years of age.

Dental maturation and eruption, epiphyseal fusion Stage Age estimate

Permanent tooth development Tooth 38: R 15.9 1.62 years

Dental eruption All teeth erupted 21 + years
Epiphyseal fusion Scapula acromium closed (>17 years); distal radius open (<19 years) 18 years

Cranial measurement Length (cm) Age range

Cranial maximum length 18.0 n/a

Cranial maximum breadth 14.7 1316 years
Cranial maximum height 13.1 >1920 years
Frontal arc 13.5 >16 years

Post-cranial measurement L (cm) R (cm) Age range Comments

Clavicle length n/o 13.1 1516 years

Scapula length (aka height or anatomical breadth) n/o n/o n/o
Scapula width (aka breadth or anatomical length) n/o n/o n/o
Supra-scapula height n/o n/o n/o
Humerus maximum length 30.8 31.3 14 years
Radius maximum length 21.2 21.2 12 years Distal metaphysis not fused
Ulna maximum length 23.7 23.6 13 years Distal metaphysis not fused
Iliac breadth (aka width) n/o 14.7 18.4 years
Iliac length 30.1 30.3 >16 years Reached maximum range of method
Femur maximum length 43.3 44.6 13 years
Tibia length 35.8 36.2 12 years
Fibula maximum length 34.1 n/o 12 years

Metaphyseal aring or chevron-circumex shape Absent

Lumbar vertebra neural canal sagittal diameter (in mm) L1 = 14.68, L2 = 13.67, L3 = 11.22, L4 = 11.55, L5 = 12.24
Lower vertebra pedicle length (in mm) T9 = 11.89, T10 = 11.15, T11 = 10.43, T12 = 15.83, L1 = 14.61, L2 = 14.25, L3 = 13.75, L4 = 15.14, L5 = 15.11
Lumbar vertebra interpedicular distance (in mm) L1 = 22.93, L2 = 22.76, L3 = 22.05, L4 = 22.00, L5 = 25.85. (Size should increase from L1 to L5)

Stature reconstruction (Fully method) 158.6 cm Just over 3 standard deviations below average young and middle aged male
stature (n = 43; 172.87 4.75 cm)
Archival stature entry 158.5 cm Tall enough to be deemed t for military service (excluded only if <155.0 cm)

n/a = not applicable; n/o = not observable.

Fig. 7. Radiograph of right femora of three perinate offspring of Sara R. (V0884,

V0486, V0485). Note lack of translucency of proximal metaphyseal region, as well
overall normal size and shape.

Fig. 6. Thoracic vertebrae 58 and lumbar vertebrae 45 (ordered left to right) from
individual V0945. Note narrow neural canals, possibly causing spinal stenosis.
clavicle is also shorter than known age, being the length of a 1516-
year-old, but not as dissimilar as the limb long bones. The ilia are
of a size consistent with age.
Stature reconstruction gives an estimate of 158.6 2.0 cm.
Military records are in agreement with this estimate and list Pieter
O.s height as 158.5 cm. This height is just over three standard
deviations below mean young and middle-aged adult male stature
from Middenbeemster (n = 43; 172.9 4.8 cm). Other post-cranial
features common to achondroplasia are absent in individual
V0963: no tibial bowing, normal os coxa morphology, no changes
in the hand or foot bones, and normal rib size. In bones where the
epiphyseal fusion line is still visible, there is no evidence of ared
or abnormally shaped metaphyses. Finally, the skull and mandible
are normal, although the foramen magnum is oval in shape.
Overall vertebral morphology is also normal. However, while
lumbar vertebrae pedicle lengths are larger than in clinically doc-
umented achondroplastics, they are one-and-a-half to ve mm
below the mean reported for normal individuals (Srikumaran et al.,
2007; Urrutia et al., 2009). Most relevant, there is a lack of caudad
increase in interpedicular distance from lumbar vertebrae 1 to 4
(Table 6), and the lumbar interpedicular distances are below the
 A.L. Waters-Rist, M.L.P. Hoogland / International Journal of Paleopathology 3 (2013) 243256
Fig. 8. Cranium of individual V0716. Identied as a 10-year old female named Hessel O. (daughter of Sara R.). Top left = front; bottom left = side; Top right = superior; bottom
right = inferior. Note enlarged vault (macrocephaly).
range documented by Hinck et al. (1966) for normal males of Euro-
pean ancestry. The lumbar neural canal sagittal diameters are also
below the mean of normal adults males as reported by Hinck et al.
(1965) (by 9.112.3 mm).
4. Discussion
4.1. Diagnosis of disproportionate dwarsm
Diagnosis of the condition affecting individual V0945 must
include recognition that it is unlikely that a skeletal dysplasia is
the sole contributor to her skeletal changes. Robust muscle attach-
ments are frequently observed in achondroplastic individuals (Jaffe,
1972), and joint laxity or malalignment is often present (Richette
et al., 2008), which can lead to the early onset and increased
severity of osteoarthritis. However, large muscle attachments and
osteoarthritis are also often related to an active lifestyle, and data
from musculoskeletal markers and bone morphology suggest that
the inhabitants of Middenbeemster were very active (Palmer et al.,
2013; Saers, 2012). Thus, it is likely that an active lifestyle for most
251
of Sara R.s life contributed to the robusticity of muscle attachments
and severity of osteoarthritis.
Here it is necessary to discount the diagnosis of pseudoachon-
droplasia, which is a genetic defect of the cartilage matrix that
results in short-limb dwarsm and precocious osteoarthritis with-
out the characteristic facial features of achondroplasia (Briggs and
Wright, 2004). Osteoarthritis may begin during adolescence and
almost always by early adulthood, mostly affecting weight-bearing
joints, and typical osseous changes include an abnormal femoral
head and neck and small, irregularly shaped hand bones (Briggs
and Wright, 2004). The osteoarthritis in individual V0945 does not
t this pattern, and the other features are absent. The osteoarthri-
tis of individual V0945 is easily explained by her age and living
conditions and should not be interpreted as pseudoachondroplasia.
Osteoporosis is also commonly observed in achondroplastic
individuals being related to low serum alkaline phosphatase levels
(Arita et al., 2012) but is a common condition in older indi-
viduals; modern studies show that it is especially common in
post-menopausal females (Krger et al., 1994). Thus, in V0945,
osteoporosis is most likely the result of a combination of advanced
252 A.L. Waters-Rist, M.L.P. Hoogland / International Journal of Paleopathology 3 (2013) 243256
Fig. 9. Skeleton of individual V0963. Identied as 21-year old male named Pieter O.
(son of Sara R.).
age and achondroplasia or hypochondroplasia. Individual V0945
had small neural canal sagittal diameters for all the thoracic and
lumbar vertebrae, with especially narrowed canals in the fourth
and fth lumbar and fth to eighth thoracic vertebrae that, in later
life, may have caused neural complications that limited activity
and contributed to bone loss. While there is no direct associa-
tion between canal size and stenosis (Wynne-Davies et al., 1981),
clinical study has found that by the sixth decade over 80% of
achondroplastics experienced stenosis-related neurological com-
plications such as back and lower limb pain, limping, accid
paralysis, and even paraplegia (Hunter et al., 1998; also see Bethem
et al., 1981; Gil et al., 2001). As noted above, Sara R.s pronounced
muscle attachments suggest an active lifestyle for most of her life,
but this likely declined in later years. Overall, while it is likely that
activity and age related factors added to the skeletal changes in
individual V0945, they could not have caused the more pathog-
nomonic changes of disproportionate dwarsm.
Continuation of the diagnostic process necessitates that features
of other diseases present in the Middenbeemster population must
also be considered for their possible role in the osseous changes of
individual V0945. Bowing of the femora is not a universal character-
istic of achondroplasia, although it is sometimes observed clinically
(e.g. Boulet et al., 2009; Cheema et al., 2003; Rump et al., 2006). The
bowing of the femora may be a reaction to the more commonly
observed tibial bowing. Genu varum is common in achondroplasia,
beginning in subadulthood (Kopits, 1989), due to bular over-
growth causing deviation in the normal medial proximal tibial
angle and mechanical axial deviation (Lee et al., 2007) and possibly
laxity of the lateral collateral ligament (Bailey, 1970; Stanley et al.,
2002). Bowlegged deformities occur in 4090% of achondroplastic
adults (depending largely on how bowing is dened and measured)
(Hunter et al., 1998, Richette et al., 2008). Yet, given individual
V0945s relatively rare femoral bowing and the severity of the resul-
tant genu varum, the role of a vitamin D deciency during growth
must be considered. Indeed, infants (birth to 3 years) from Midden-
beemster have a rather high prevalence of rickets (33.3%) (Veselka
et al., 2013), and it is possible that a vitamin D deciency exacer-
bated the degree of bowing. This may lead some to the question if
the skeletal changes in V0945 could be the result of rickets, nor-
mal age-related degenerative processes, combined with normal
or idiopathic short stature. Idiopathic short stature is stature more
than two standard deviations below the population mean with no
identiable hormonal, chromosomal, or genetic cause, or other evi-
dence of a specic growth retarding condition. That is, is it possible
individual V0945 actually did not have a skeletal dysplasia?
We argue strongly against this possibility for several reasons.
Firstly, the morphology of the cranium would not be accounted for
in this scenario. Secondly, only in the most extreme case of rick-
ets would an individuals stature be reduced to dwarf proportions.
Thirdly, the strongest argument against the possibility that her
short stature could be the result of a normal genetic predisposition,
possibly exacerbated by malnutrition and/or vitamin D deciency
during subadulthood, are the nature of the limb bone changes:
the fact that the axial skeleton and slower growing bones are of
more normal size. Simple short stature would not result in dis-
proportionately sized skeletal segments, wherein bones that grow
via endochondral ossication, and with faster growth rates, are
most affected. Fourthly, only achondroplasia or hypochondropla-
sia would cause shortened pedicles and the lack of caudad increase
in lumbar interpedicular distance. Finally, support of this diagnosis
is offered if we accept that two of her offspring have osteological
changes consistent with disproportionate dwarsm.
The shortened limb long bones of the ten-year-old daughter
could be evidence for a skeletal dysplasia. However, in consider-
ing this possibility, it should be kept in mind that she had slight to
moderate delayed maturation of the entire skeleton and dentition,
suggesting an overall developmental lag. Yet, her macrocephalic
cranium would not be due to a developmental lag, and when com-
bined with other data including inconsistent lumbar interpedicular
distance increase, it is support for a diagnosis of disproportionate
dwarsm. Similarly, a diagnosis of disproportionate dwarsm is
suggested for the 21-year-old son by shortened limb bones and a
lack of caudad interpedicular distance increase.
The adult sons mesomelia pattern of limb bone shortening
makes it necessary to consider the diagnosis of a SHOX (Short-
stature HOmeoboX-containing gene) mutation. Since its discovery
in 1997 (Ellison et al., 1997; Rao et al., 1997), a SHOX mutation has
been shown to be responsible for growth retardation in Lri-Weill
dyschondrosteosis, Langer mesomelic dysplasia, and Turner syn-
drome (Grigelioniene et al., 2000; Munns and Glass, 2008), and the
cause of short stature in one to twelve percent of cases of idiopathic
 A.L. Waters-Rist, M.L.P. Hoogland / International Journal of Paleopathology 3 (2013) 243256
short stature (Rao et al., 1997; Rappold et al., 2002; Schneider et al.,
2005; Stuppia et al., 2003). While there is considerable phenotypic
variability, SHOX mutations typically cause a mesomelia pattern
of long bone shortening (forearms and lower legs most affected),
bilateral shortening and bowing of the radius with dorsal sublux-
ation of the distal ulna and wedged carpal bones (Madelung wrist
deformity), and short metacarpals/metatarsals (especially in the
4th metacarpal) (Hintz, 2002; Leka et al., 2006). Individual V0963s
radii and ulnae are shortened but are otherwise morphologically
normal, as are the carpal bones, and the metacarpals/tarsals are
of normal size. Moreover, limb bone shortening in achondropla-
sia/hypochondroplasia includes both rhizomelic (Frydman et al.,
1974) and mesomelic (Beals, 1969; Song et al., 2012; Walker et al.,
1971) patterns, sometimes with a predominance of neither (Hall
and Spranger, 1979). Thus, we consider it unlikely that individual
V0963 had a SHOX mutation.
It is argued, therefore, that the disease that affected individ-
ual V0945 and at least two of her offspring was achondroplasia
or hypochondroplasia. Which of these two disorders is most con-
sistent with the skeletal changes is discussed below. In order to
properly consider all of the evidence, a section discussing the
manifestation of disproportionate dwarsm in subadults is rst
presented.
4.1.1. Disproportionate dwarsm in infancy and childhood
Disproportionate dwarsm presents differently in infancy and
childhood as skeletal size is less reduced relative to adults. Few
archaeological examples exist, although Sables (2010) reports on
an infant skeleton of 1824 months from an early Mediaeval Welsh
cemetery that is purported to be an achondroplastic dwarf on the
basis of shortened and thickened long bones (the size of an 812
month-old), ared long bone metaphyses, slight tibial bowing, and
normal trunk size. It is not until after the age of three years that the
achondroplasia and normal height growth curves no longer overlap
(Horton et al., 1978, 2007). Prior to the advent of modern scan-
ning technology delayed skeletal growth of achondroplastics was
not usually noted until after the age of one year. In milder achon-
droplastic phenotypes, or the less severe hypochondroplasia, it may
not be noted until later childhood or even adolescence (Appan et al.,
1990; Francomano, 2005; Horton et al., 1978). Thus, the lack of evi-
dence for reduced skeletal size in the three perinate offspring of
individual V0945 should not be interpreted as denitive proof that
they were not affected. Indeed, given that each had a fty percent
chance of being affected it is unlikely none were. Kozma et al. (2011)
discuss a female skeleton from Egypt with marked dwarsm dis-
covered with a foetal skeleton in her pelvic cavity. While the foetal
bones were of the size of a late or full-term foetus and of normal
morphology, Kozma et al. (2011) similarly conclude that dwarsm
cannot be excluded because it may have not yet manifested in the
observable skeletal remains.
While post-cranial size is less diagnostic for disproportionate
dwarsm in infants and children than for adults, the cranium can
be the rst indication of pathology. Horton et al. (1978) report that
at birth most achondroplastics are macrocephalic with a mean head
circumference two standard deviations above normal. Rapid head
growth occurs during the rst year leading to a further increase
above normal (Horton et al., 1978). However, there is considerable
overlap in head circumference between achondroplastic and nor-
mal individuals (Horton et al., 1978), so in cases of affected infants
with just moderately large or normally sized crania a skeletal dys-
plasia would not be detected.
As three of individual V0945s offspring died as perinates, the
phenotypic changes of disproportionate dwarsm may have been a
contributory factor. Delivery of a macrocephalic infant will increase
the mortality risk to mother and child (e.g. Kozma et al., 2011):
this, along with the small pelvis of individual V0945, may have
253
been factors in the deaths of the three perinates. However, archival
sources and skeletal data show that infant mortality was high in the
Middenbeemster population with the death of three out of seven
offspring during the neonatal period not uncommon.
4.1.2. Diagnosis of achondroplasia versus hypochondroplasia
Considered alone, the suite of features of individual V0945
would probably lead to a diagnosis of achondroplasia, albeit of a
milder phenotypic form than most archaeologically documented
dwarfs. In this respect it is important to note that in paleopathol-
ogy it is often the more severe examples that are detected and
published. In contextualising the extent of long bone shorten-
ing in individual V0945 a useful table from Slon et al. (2011:
Table 5) presents the metrics from seven archaeological dwarfs
(Th-231 from Slon et al. (2011), Romito 2 from Frayer et al.
(1988), Moundville male and female by Snow (1943), Coxyde
from Susanne (1970) and Polet and Orban (1996), Gotland by Larje
(1985), and CA-Sac-127 from Hoffman (1976)). Individual V0945
has long bone maximum lengths that are greater by 6090 cm than
all but one of the dwarfs. Only the Gotland dwarf has long bones
that are longer than those of individual V0945. Nonetheless, the
long bones are clearly shortened and the other skeletal features
would make achondroplasia a likely diagnosis. The features com-
mon to achondroplasia that individual V0945 lacks are not always
present so would not be considered especially problematic.
Considered alone, the suite of features in the 10-year-old daugh-
ter and 21-year-old son would likely not have resulted in a
diagnosis of achondroplasia, or even hypochondroplasia. For both
individuals, a simple explanation of idiopathic short stature pos-
sibly exacerbated by growth stunting due to deleterious dietary
or health conditions, is most likely. Indeed, individual V0963 had
several marked linear enamel hypoplasia defects that suggest he
experienced serious stress episodes during childhood that could
have impacted his growth. As well, the ten-year-old daughters
macrocephalic cranium could have been caused by a number of
health conditions (i.e. megalencephaly, hydrocephalus, subdural
haematoma, neonatal intraventricular haemorrhage, autism, and
a host of rare genetic diseases), so dwarsm would not normally be
the rst diagnostic suggestion.
Thus, having the family history and considering the overall pat-
tern of skeletal changes in several purportedly affected individuals
is incredibly informative in this example. With all individuals con-
sidered together, we suggest that a diagnosis of hypochondroplasia
best accounts for their pattern of skeletal changes. The extent of
limb bone shortening in the adults ts better with a diagnosis of
hypochondroplasia than achondroplasia. In typical achondroplasia,
the femur and tibia are eight and seven standard deviations below
normal size (Nehme et al., 1976). V0945s femora and tibiae are
ve and four standard deviations, respectively, below the Midden-
beemster female mean. Individual V0963s femora and tibiae are
three standard deviations below the Middenbeemster male mean.
The close agreement of the estimated and archival stature informa-
tion for individual V0963 is worth noting and supports the accuracy
of the Fully (1956) anatomical method for stature reconstruction in
individuals of small stature.
In hypochondroplasia most researchers report that facial
changes do not occur (Francomano, 2005; Langer et al., 1967;
Wynne-Davies et al., 1981), although Oberklaid et al. (1979) found
little difference in the abnormal facial morphology of achon-
droplastic versus hypochondroplastic patients. So it is possible
that the normal facial morphologies of the older offspring sup-
port a diagnosis of hypochondroplasia. Hall and Spranger (1979)
found that macrocephaly was present in approximately 50% of the
hypochondroplasia cases they reviewed, thus tting the fact that
one out of the two observable offspring had this feature and that it
was absent in individual V0945.
254 A.L. Waters-Rist, M.L.P. Hoogland / International Journal of Paleopathology 3 (2013) 243256
The lack of a trident hand pattern in individual V0945 and her
offspring is relevant for the distinction between achondroplasia
and hypochondroplasia. The trident pattern is present in approx-
imately half of achondroplastics (Ortner and Putschar, 1981). In
hypochondroplasia, the hand long bones may be relatively short but
they never exhibit the trident appearance typical of achondroplasia
(Francomano, 2005).
Also in hypochondroplasia, pelvis shape is normal (no squared
ilia, narrow greater sciatic notches, or shortened pubi or ischiums)
(Wynne-Davies et al., 1981). Matsui et al. (1998) computed the
pelvic index as the ratio of the interteardrop distance to pelvic
width in achondroplastic, hypochondroplastic, and normal subjects
and found no statistical difference between the hypochondroplas-
tic and normal group. Thus, the normal os coxa shapes in the
adult individuals ts best with the documented morphology of
hypochondroplasia. As well, in hypochondroplasia it is less likely
that the acetabular roofs be attened (Francomano, 2005), a feature
not seen in any of the three purportedly affected individuals.
Wynne-Davies et al. (1981) found that bular length was greater
than tibial length in all achondroplastic and three-quarters of
hypochondroplastics subjects, with marked genu varum in 15%
of achondroplastics and eight percent of hypochondroplastics.
Stanley et al. (2002) used bula to tibia length to establish a ratio,
with achondroplastics always having a ratio greater than 0.98, as
a key factor causing bowed legs (but see Ain et al., 2006). Indeed,
individual V0945 has a ratio above 0.98, at 1.03, and there is marked
genu varum. The juvenile daughter has bulaetibiae lengths that
are roughly equal resulting in a ratio above 0.98, at 1.00, but the
lack of overgrowth may be a factor in why she does not have bowed
legs. In the young adult son the tibiae are longer than the bulae
by 1.72.1 cm, resulting in a ratio of 0.940.95, thus also explaining
the lack of bowing. Thus, in regards to a diagnosis of achondropla-
sia versus hypochondroplasia the morphology of the two older
offspring are more concordant with hypochondroplasia.
In regards to the lack of caudad increase of lumbar interpedi-
cle distance, hypochondroplasia in its most severe form overlaps
with the achondroplasia range and in its least severe form over-
laps with the normal range (Wynne-Davies et al., 1981). For lumbar
vertebrae 14, 16.7% of hypochondroplastics had decreased inter-
pedicle distances, with the other 83.3% having equal interpedicle
distances; importantly, none of the hypochondroplastics had pro-
gressively increasing interpedicle distances (Wynne-Davies et al.,
1981). Clearly the interpedicle distances of this family t well
within the range and pattern of hypochondroplastics.
In growing hypochondroplastic individuals it is rare that the dis-
tal femur metaphysis takes on a chevron deformity (Francomano,
2005), which ts with the juvenile and young adult offspring.
Finally, the lack of evidence for disproportionate dwarsm in the
three perinates is consistent with a diagnosis of hypochondroplasia,
because while it is of course possible none of them were affected,
one or more of them may have been affected with skeletal evidence
yet to be manifested.
Achondroplasia is associated with advanced paternal age (>35
years) (Oberklaid et al., 1979; Orioli et al., 1995). Individual V0945s
father was 38 years of age at conception (the mother was 43 years
of age). Some researchers have found that increased paternal age
is also associated with hypochondroplasia (e.g. Maroteaux and
Falzon, 1988), while others have found no such association (e.g.
Wynne-Davies et al., 1981). Thus, the age of individual V0945s
father may increase our knowledge about the relationship between
hypochondroplasia and paternal age.
It must be kept in mind that it is difcult to diagnose hypochon-
droplasia based on macroscopic and radiographic measures, even
in clinical contexts (Rousseau et al., 1996). The wide range of
phenotypic changes within hypochondroplasia, combined with
overlapping ranges for achondroplastic and normal individuals,
make the diagnostic process challenging (Rousseau et al., 1996;
Scott, 1976). As many features as possible must be assessed, as was
done in this case. Overall we argue that the pattern of phenotypic
changes in this family best supports a diagnosis of hypochondropla-
sia. To our knowledge, the diagnosis of hypochondroplasia has
never been made for skeletal remains from an archaeological con-
text. This is not that surprising as the morphological changes are not
severe and shortened limb bones may be simply attributed to idio-
pathic short stature. We recommend that in future archaeological
cases of markedly short subadults or adults, especially with oth-
erwise normal or near-normal features, the interpedicle distance
of the lumbar spine be measured to determine if there is a lack of
caudad increase, as this proved very useful.
5. Conclusions
In conclusion, this case study presents a compelling example of
the value of family history data in the diagnostic process, something
which is rare in paleopathology. The FGFR3 mutation conditions,
achondroplasia and hypochondroplasia, were discussed and evalu-
ated for a mother and her ve offspring buried at the predominately
nineteenth century site of Middenbeemster, The Netherlands. We
argue that the suite of characteristics present in this family best
correspond to a diagnosis of hypochondroplasia.
No invariable clinical or radiological feature will distinguish
hypochondroplasia from achondroplasia only genetic testing will
provide an exact diagnosis. In 2004 Pusch et al. attempted to
identify achondroplastic mutations in prehistoric bone samples
but faced complications with PCR-induced sequence alterations.
It is hoped that DNA sequencing of archaeologically derived bone
samples for FGFR mutations can be reattempted and that it will
prove possible to conrm which form of disproportionate dwarsm
occurred in this family.
Acknowledgements
We thank graduate students of the MSc osteoarchaeology
program at Leiden for their contribution to the analysis of the
Middenbeemster material. Annick Meurrens is thanked for ini-
tial observation and she and Frank van Spelde are acknowledged
for taking photographs. We thank Jaap Saers for taking CT-scans
and helping with image formatting, and Dr. Rick van Rjin of the
Academic Medical Centre, Amsterdam, for allowing access to and
training on the CT-machine. We thank Joost Roelofs of the Leiden
University Medical Centre for assistance with radiographs. Thanks
to Rachel Schats for providing useful feedback on an early ver-
sion of this manuscript and to Prof. George Maat and Dr. Hans de
Boer for being our sounding board and providing helpful advice.
Finally, thanks to the associate editor and anonymous reviewers
for suggestions that improved this manuscript.
References
Ain, M.C., Shirley, E.D., Pirouzmanesh, A., 2006. Genu varum in achondroplasia. Jour-
nal of Pediatric Ophthalmology 26, 375379.
Allanson, J.E., Hall, J.G., 1986. Obstetric and gynecologic problems in women with
chondrodystrophies. Obstetrics and Gynecology 67, 7478.
Almeida, M.R., Campos-Xavier, A.B., Medeira, A., Cordeiro, I., Sousa, A.B., Lima, A.,
Soares, G., Rocha, M., Saraiva, J., Ramos, L., Sousa, S., Marcelino, J.P., Correia,
A., Santos, H.G., 2009. Clinical and molecular diagnosis of the skeletal dyspla-
sia associated with mutations in the gene encoding broblast growth factor
receptor 3 (FGFR3) in Portugal. Clinical Genetics 75, 150156.
Appan, S., Laurent, S., Chapman, M., Hindmarsh, P.C., Brook, C.G.D., 1990. Growth and
growth hormone therapy in hypochondroplasia. Acta Paediatrica Scandinavica
79, 796803.
Arcini, C., Frlund, P., 1996. Two dwarves from Sweden: a unique case. International
Journal of Osteoarchaeology 6, 155166.
 A.L. Waters-Rist, M.L.P. Hoogland / International Journal of Paleopathology 3 (2013) 243256
Arita, E.S., Pippa, M.G.B., Marcucci, M., Cardoso, R., Cortes, A.R.G., Watanabe, P.C.A.,
Oliveira, J.X., 2012. Assessment of osteoporotic alterations in achondroplastic
patients: a case series. Clinical Rheumatology, 14.
Bagnall, K.M., Harris, P.F., Jones, P.R.M., 1977. A radiographic study of the human
spine. II. The sequence of development of ossication centres in the vertebral
column. Journal of Anatomy 124, 791802.
Bailey II, J.A., 1970. Orthopaedic aspects of achondroplasia. Journal of Bone and Joint
Surgery, American Volume 52-A, 12851301.
Beals, R.K., 1969. Hypochondroplasia: a report of ve kindreds. Journal of Bone and
Joint Surgery, American Volume 51-A, 728736.
Bellus, G.A., McIntosh, I., Smith, E.A., Aylsworth, A.S., Kaitila, I., Horton, W.A., Green-
haw, G.A., Hecht, J.T., Francomano, C.A., 1995. A recurrent mutation in the
tyrosine kinase domain of broblast growth factor receptor 3 causes hypochon-
droplasia. Nature Genetics 10, 357359.
Bellus, G.A., McIntosh, I., Szabo, J., Aylsworth, A., Kaitila, I., Francomano, C.A., 1996.
Hypochondroplasia: molecular analysis of the broblast growth factor receptor
3 gene. Annals of the New York Academy of Sciences 785, 182187.
Bernal, J., Briceno, I., 2006. Genetic and other diseases in the pottery of Tumaco-La
Tolita culture in ColombiaEcuador. Clinical Genetics 70, 188191.
Bethem, D., Winter, R.B., Lutter, L., Moe, J.H., Bradford, D.S., Lonstein, J.E., Langer,
L.O., 1981. Spinal disorders of dwarsm. Review of the literature and report
of eighty cases. Journal of Bone and Joint Surgery, American Volume 63,
14121425.
Black, S.M., Scheuer, J.L., 1996. Age changes in the clavicle: from the early neona-
tal period to skeletal maturity. International Journal of Osteoarchaeology 6,
425434.
Boulet, S., Althuser, M., Nugues, F., Schaal, J.P., Jouk, P.S., 2009. Prenatal diagnosis of
achondroplasia: new specic signs. Prenatal Diagnosis 29, 697702.
Briggs, M.D., Wright, M.J., 1993. Pseudoachondroplasia. 2004 August 20 [Updated
2013 February 28]. In: Pagon, R.A., Bird, T.D., Dolan, C.R., et, al. (Eds.),
GeneReviewsTM [Internet]. University of Washington, Seattle, Seattle, WA, Avail-
able from: http://www.ncbi.nlm.nih.gov/books/NBK1487/
Buckberry, J.L., Chamberlain, A.T., 2002. Age estimation from the auricular surface
of the ilium: a revised method. American Journal of Physical Anthropology 119,
231239.
Buikstra, J.E., Ubelaker, D. (Eds.), 1994. Standards for Data Collection from Human
Skeletal Remains: Proceedings of a Seminar at the Field Museum of Natural
History. Arkansas Archaeological Survey Press, Fayetteville.
Cheema, J.I., Grissomm, L.E., Harcke, H.T., 2003. Radiographic characteristics of
lower-extremity bowing in children. Radiographics 23, 871880.
Dekaban, A.S., 1977. Tables of cranial and orbital measurements, cranial volume, and
derived indexes in males and females from 7 days to 20 years of age. Annals of
Neurology 2, 485490.
Demirjian, A., Goldstein, H., Tanner, J.M., 1973. A new system of dental age assess-
ment. Human Biology 45 (2), 211227.
Deng, C., Wynshaw-Boris, A., Zhou, F., Kuo, A., Leder, P., 1996. Fibroblast growth
factor receptor 3 is a negative regular of bone growth. Cell 84, 911921.
Ellison, J.W., Wardak, Z., Young, M.F., Gehron Robey, P., Laig-Webster, M., Chiong,
W., 1997. PHOG, a candidate gene for involvement in the short stature of Turner
syndrome. Human Molecular Genetics 6, 13412134.
Enderle, A., 1998. Dwarsm and gigantism in historical picture postcards. Journal of
the Royal Society of Medicine 91, 273278.
Farkas, G., Nagy, E., Ksa, F., 2001. Skeleton of a dwarf from excavations. Acta Bio-
logica Szegediensis 45, 7982.
Fazekas, I.G., Kosa, F., 1978. Forensic fetal osteology. Akademiai Kaido, Budapest.
Francomano, C.A., 2005. Hypochondroplasia. First published 1999 July 15, updated
2005 December 12. In: Pagon, R.A., Bird, T.D., Dolan, C.R. (Eds.), GeneReviewsTM
[Internet]. University of Washington, Seattle, Seattle, WA, Available from:
http://www.ncbi.nlm.nih.gov/books/NBK1477/
Frayer, D.W., Macchiarelli, R., Mussi, M., 1988. A case of chondrodystrophic dwarsm
in the Italian late upper Paleolithic. American Journal of Physical Anthropology
75, 549565.
Frydman, M., Hertz, M., Goodman, R.M., 1974. The genetic entity of hypochondropla-
sia. Clinical Genetics 5, 223229.
Fully, G., 1956. Une nouvelle methode de determination de la taille. Annales de
Mdecine Lgale 35, 266273 (in French).
Ghumman, S., Goel, N., Rajaram, S., Singh, K.C., Kansal, B., Dewan, P., 2005. Preg-
nancy in an achondroplastic dwarf: a case report. Journal of the Indian Medical
Association 103, 536538.
Gil, Z., Tauman, R., Sivan, J., Orr-Urtreger, A., Constantini, S., 2001. Neurosur-
gical aspects in achondroplasia evaluation and treatment. Harefuah 140,
10261031.
Gadykowska-Rzeczycka, J., 1980. Remains of achondroplastic dwarf from Legnica
of XIXIIth century. Ossa 7, 7174.
Grigelioniene, G., Eklof, O., Ivarson, S.A., Westphal, O., Neumeyer, L., Kedra, D.,
Dumanski, J., Hagenas, L., 2000. Mutations in short stature homeobox contain-
ing gene (SHOX) in dyschondrosteosis but not in hypochondroplasia. Human
Genetics 107, 145149.
Hall, B.D., Spranger, J., 1979. Hypochondroplasia: clinical and radiological aspects in
39 cases. Radiology 133, 95100.
Haworth, J.C., Chudley, A.E., 2001. Dwarfs in art. Clinical Genetics 59 (2),
8487.
Hecht, J., Butler, I.J., 1990. Neurologic morbidity associated with achondroplasia.
Journal of Child Neurology 5, 8497.
Hinck, V.C., Hopkins, C.E., Clark, W.M., 1965. Sagittal diameter of the lumbar canal
in children and adults. Radiology 85, 929937.
255
Hinck, V.C., Clark, W.M., Hopkins, C.E., 1966. Normal interpediculate distances (mini-
mum and maximum) in children and adults. American Journal of Roentgenology
97, 141153.
Hintz, R., 2002. SHOX mutations. Reviews in Endocrine and Metabolic Disorders 3,
363367.
Hoffman, J.M., 1976. An achondroplastic dwarf from the Augustine site (CA-Sac-127).
Contributions of the University of California Archaeological Research Facility 30,
65119.
Horton, W.A., Rotter, J.I., Rimoin, D.L., Scott, C.I., Hall, J.G., 1978. Standard growth
curves for achondroplasia. Journal of Pediatrics 93, 435438.
Horton, W.A., Hall, J.G., Hecht, J.T., 2007. Achondroplasia. Lancet 370, 162172.
Humphrey, L.T., Scheuer, L., 2006. Age of closure of the foramen of Huschke: an
osteological study. International Journal of Osteoarchaeology 16, 4760.
Hunter, A.G.W., Hecht, J.T., Scott, C.I., 1996. Standard weight for height curves in
achondroplasia. American Journal of Medical Genetics 62, 255261.
Hunter, A.G.W., Bankier, A., Roberts, J.G., Sillence, D., Scott, C.J., 1998. Medical compli-
cations of achondroplasia: a multiple patient review. Journal of Medical Genetics
35, 705712.
Iscan, M.Y., Loth, S.R., 1986. Determination of age from the sternal rib in white
females: a test of phase method. Journal of Forensic Sciences 31, 990999.
Jaffe, H.L., 1972. Metabolic, Degenerative and Inammatory Diseases of Bones and
Joints. Lea & Febiger, Philadelphia.
Jeong, S.T., Song, H.R., Keny, S.M., Telang, S.S., Suh, S.W., Hong, S.J., 2006. MRI study of
the lumbar spine in achondroplasia. A morphometric analysis for the evaluation
of stenosis of the canal. Journal of Bone & Joint Surgery - British Volume 88 (9),
11921196.
Knol, E., Prummel, W., Uytterschaut, H.T., Hoogland, M.L.P., Casparie, W.A., DeLan-
gen, G.J., Kramer, E., Schelvis, J., 1996. In: Palaeohistoria 37/38, Altema, P.A.J.,
Bierma, M., Hoekstra, T.R., Lanting, J.N., Weijns, M. (Eds.), The Early Medieval
Cemetery of Oosterbeintum (Friesland). A.A. Balkema, Rotterdam, pp. 245416.
Kopits, S.E., 1989. Orthopedic aspect of achondroplasia in children. Basic Life Sci-
ences 48, 189197.
Kozma, C., 2006. Historical reviewdwarfs in ancient Egypt. American Journal of
Medical Genetics 140A, 303311.
Kozma, C., Sarry El Din, A.M., El Shafy Banna, R.A., El Samie Kandeel, W.A., Lachman,
R., 2011. Genetic drift. The ancient Egyptian dwarfs of the pyramids: the high
ofcial and the female worker. American Journal of Medical Genetics Part A 155A
(8), 18171824.
Krger, H., Tuppurainen, M., Honkanen, R., Alhava, E., Saarikoski, S., 1994. Bone min-
eral density and risk factors for osteoporosisa population-based study of 1600
perimenopausal women. Calcied Tissue International 55 (1), 17.
Kumar, C.P., Orth, M., Song, H.R., Lee, S.H., Suh, S.W., Oh, C.W., 2006. Thoracic
and lumbar pedicle morphology in achondroplasia. Clinical Orthopaedics and
Related Research 454, 180185.
Langer, L.O., Baumann, P.A., Gorlin, R.J., 1967. Achondroplasia. American Journal of
Roentgenology, Radium Therapy, and Nuclear Medicine 100, 1226.
Larje, R., 1985. The short Viking from Gotland: a case study. Archaeology and Envi-
ronment 4, 259271.
Lee, S.T., Song, H.R., Mahajan, R., Makwana, V., Suh, S.W., Lee, S.H., 2007. Develop-
ment of genu varum in achondroplasia: relation to bular overgrowth. Journal
of Bone & Joint Surgery - British Volume 89-B, 5761.
Leka, S.K., Kitsiou-Tzeli, S., Kalpini-Mavrou, A., Kanavakis, E., 2006. Short stature
and dysmorphology associated with defects in the SHOX gene. Hormones 5 (2),
107118.
Liversidge, H.M., Herdeg, B., Rosing, F.W., 1998. Dental age estimation of non-
adultsa review of methods and principles. In: Alt, K.W., Rosing, F.W.,
Teschler-Nicola, M. (Eds.), Dental Anthropology, Fundamentals, Limits and
Prospects. Springer, Vienna, pp. 419442.
Maresh, M.M., 1970. Measurements from roentgenograms. In: McCammon, R.W.
(Ed.), Human Growth and Development. Charles C. Thomas Publishers, Spring-
eld, IL, pp. 157200.
Maroteaux, P., Falzon, P., 1988. Hypochondroplasia. Review of 80 cases. Archives
Francaises de Pediatrie 45, 105109 (in French).
Matsui, Y., Yasui, N., Kimura, N., Tsumaki, N., Kawabata, H., Ochi, T., 1998. Geno-
type phenotype correlation in achondroplasia and hypochondroplasia. Journal
of Bone & Joint Surgery - British Volume 80-B, 10521056.
Meindl, S., Lovejoy, O., 1985. Ectocranial suture closure: a revised method for the
determination of skeletal age at death based on the lateral-anterior sutures.
American Journal of Physical Anthropology 68, 5766.
Moorrees, C.F.A., Fanning, E.A., Hunt, E.E., 1963. Age variation of formation. Stages
for ten permanent teeth. Journal of Dental Research 42, 14901502.
Munns, C., Glass, I., 2008. SHOX-related haploinsufciency disorders. First pub-
lished 2005 December 12, updated 2008 February 1. In: Pagon, R.A., Adam,
M.P., Bird, T.D., Dolan, C.R., Fong, C.T., Stephens, K. (Eds.), GeneReviewsTM
[Internet]. University of Washington, Seattle, Seattle, WA, Available from:
http://www.ncbi.nlm.nih.gov/books/NBK1215/
Nehme, A.E., Riseborough, E.J., Tredwell, S.J., 1976. Skeletal growth and development
of the achondroplastic dwarf. Clinical Orthopaedics and Related Research 116,
8.
Oberklaid, F., Danks, D.M., Jensen, F., Stace, L., Rosshandler, S., 1979. Achondroplasia
and hypochondroplasia. Comments on frequency, mutation rate, and radiolog-
ical features in skull and spine. Journal of Medical Genetics 16, 140146.
Oostra, R.J., Baljet, B., Dijkstra, P.F., Hennekam, R.C.M., 1998. Congenital anoma-
lies in the teratological collection of Museum Vrolik in Amsterdam, The
Netherlands. II: Skeletal dysplasias. American Journal of Medical Genetics 77 (2),
116134.
256 A.L. Waters-Rist, M.L.P. Hoogland / International Journal of Paleopathology 3 (2013) 243256
Orioli, I.M., Castilla, E.E., Scarano, G., Mastroiacovo, P., 1995. Effect of paternal age in
achondroplasia, thanaophoric dysplasia, and osteogenesis imperfect. American
Journal of Medical Genetics 59 (2), 209217.
Ortner, D.J., Putschar, W.G., 1981. Identication of Pathological Conditions in Human
Skeletal Remains. Smithsonian, Washington D.C.
Palmer, J., Hoogland, M.L.P., Waters-Rist, A.L., 2013. Activity reconstruction of post-
medieval rural Dutch villagers from osteoarthritis and musculoskeletal stress
markers. International Journal of Osteoarchaeology (submitted for publication).
Phenice, T.W., 1969. A newly developed visual method of sexing the os pubis. Amer-
ican Journal of Physical Anthropology 30, 297302.
Polet, C., Orban, R., 1996. Lachondroplase de labbaye des dunes de Coxyde
(Belgique, XIIeXVe sicles). In: 3e colloque international de pathographie,
pp. 125162.
Pusch, C.M., Broghammer, M., Nicolson, G.J., Nerlich, A.G., Zink, A., Kennerknech,
I., Bachmann, L., Blin, N., 2004. PCR-induced sequence alterations hamper the
typing of prehistoric bone samples for diagnostic achondroplasia mutations.
Molecular Biology and Evolution 21 (11), 20052011.
Rao, E., Weiss, B., Fukami, M., Rump, A., Niesler, B., Mertz, A., Muroya, K., Binder,
G., Kirsch, S., Winkelmann, M., Nordsiek, G., Heinrich, U., Breuning, M.H., Ranke,
M.B., Rosenthal, A., Ogata, T., Rappold, G.A., 1997. Pseudoautosomal deletions
encompassing a novel homeobox gene cause growth failure in idiopathic short
stature and Turner syndrome. Nature Genetics 16, 5463.
Rappold, G., Fukami, M., Niesler, B., Schiller, S., Zumkeller, W., Bettendorf, M.,
Heinrich, U., Vlachopapadoupoulou, E., Reinehr, T., Onigata, K., Ogata, T., 2002.
Deletions of the homeobox gene SHOX (short stature homeobox) are an impor-
tant cause of growth failure in children with short stature. Journal of Clinical
Endocrinology and Metabolism 87, 14021406.
Raxter, M.H., Auerbach, B.M., Ruff, C.B., 2006. Revision of the Fully technique for
estimating statures. American Journal of Physical Anthropology 130, 374384.
Richette, P., Bardin, T., Stheneur, C., 2008. Achondroplasia: from genotype to phe-
notype. Joint, Bone, Spine 75, 125130.
Rietman, A., Bol, W., Peeters, B., Rieswijk, L., van den Broek, J., Cornel, L., 2008.
Gewicht en achondroplasia. Unofcial report to the belangenvereniging voor
kleine mensen (in Dutch).
Rimoin, D.L., 1988. Clinical variability in achondroplasia. In: Nicoletti, B., Kopits,
S.E., Ascani, E., McKusick, V.A., Dryburgh, S.C. (Eds.), Human Achondroplasia: A
Multidisciplinary Approach. Plenum Press, New York, pp. 123127.
Rissech, C., Black, S., 2007. Scapular development from the neonatal period to skele-
tal maturity: a preliminary study. International Journal of Osteoarchaeology 17
(5), 451464.
Rissech, C., Malgosa, A., 2005. Ilium growth study: applicability in sex and age diag-
nosis. Forensic Science International 147, 165174.
Rodriguez, C.A., Isaza, C., Pachajoa, H., 2012. Achondroplasia among ancient popu-
lations of Mesoamerica and South America: iconographic and archaeological
evidence. Colombia Mdica 43, 212215.
Rousseau, F., Bonaventure, J., Legeai-Mallet, L., Pelet, A., Rozet, J.M., Maroteaux, P., Le
Merrer, M., Munnich, A., 1994. Mutations in the gene encoding broblast growth
factor receptor 3 in achondroplasia. Nature 371, 252254.
Rousseau, F., Bonaventure, J., Legeai-Mallet, L., Schmidt, H., Weissenbach, J., 1996.
Clinical and genetic heterogeneity of hypochondroplasia. Journal of Medical
Genetics 33, 749752.
Ruff, C.B., 2008. Biomechanical analyses of archaeological human skeletons. In:
Katzenberg, M.A., Saunders, S.R. (Eds.), Biological Anthropology of the Human
Skeleton. , 2nd ed. Wiley-Liss, New York, NY, pp. 183206.
Rump, P., Letteboer, T.G.W., Gille, J.J.P., Torringa, M.J.L., Baerts, W., van Gestel, J.P.J.,
Verheij, J.B.G.M., van Essen, A.J., 2006. Severe complications in a child with
achondroplasia and two FGFR3 mutations on the same allele. American Journal
of Medical Genetics 140-A, 284290.
Sables, A., 2010. Rare example of an early medieval dwarf infant from Brownslade,
Wales. International Journal of Osteoarchaeology 20, 4753.
Saers, J., 2012. Sexual Division of Labour in Rural 17th to 19th Century Holland:
A Study of Limb Bone Cross-sectional Geometry. Leiden University, Faculty of
Archaeology (MSc thesis).
Saunders, S., Hoppa, R., Southern, R., 1993. Diaphyseal growth in a nineteenth cen-
tury skeletal sample of subadults from St Thomas Church, Belleville, Ontario.
International Journal of Osteoarchaeology 3, 265281.
Schaefer, M., Scheuer, L., Black, S., Schaefer, M.C., 2009. Juvenile Osteology: A Labo-
ratory and Field Manual. Academic Press, London, U.K.
Scheuer, J.L., MacLaughlin-Black, S., 1994. Age estimation from the pars basilaris of
the fetal and juvenile occipital bone. International Journal of Osteoarchaeology
4, 377380.
Scheuer, J.L., Black, S.M., 2004. The Juvenile Skeleton. Elsevier, London.
Schneider, K.U., Sabherwal, N., Jantz, K., Rth, R., Muncke, N., Blum, W.F., Cutler
Jr., G.B., Rappold, G., 2005. Identication of a major recombination hotspot in
patients with short stature and SHOX deciency. American Journal of Human
Genetics 77, 8996.
Scott, C.I., 1976. Achondroplastic and hypochondroplastic dwarsm. Clinical
Orthopaedics and Related Research 114, 18.
Shiang, R., Thompson, L.M., Zhu, Y.Z., Church, D.M., Fielder, T.J., Bocian, M., Winokur,
S.T., Wasmuth, J.J., 1994. Mutations in the transmembrane domain of the FGFR3
cause the most common genetic form of dwarsm, achondroplasia. Cell 78,
335342.
Slon, V., Nagar, Y., Kuperman, T., Hershkovitz, I., 2011. A case of dwarsm from the
Byzantine city Rehovot-in-the-Negev, Israel. International Journal of Osteoar-
chaeology, http://dx.doi.org/10.1002/oa.1285.
Snow, C.E., 1943. Two prehistoric Indian dwarf skeletons from Moundville. Alabama
Museum of Natural History Paper 21, 190.
Sommer, A., Young-Wee, T., Frye, T., 1987. Achondroplasiahypochondroplasia com-
plex. American Journal of Medical Genetics 26, 949957.
Song, S.-H., Balce, G.C.E., Agashe, M.V., Lee, H., Hong, S.-J., Park, Y.-E., Kim, S.-G.,
Song, H.-R., 2012. New proposed clinico-radiologic and molecular criteria in
hypochondroplasia: FGFR 3 gene mutations are not the only cause of hypochon-
droplasia. American Journal of Medical Genetics 158A, 24562462.
Srikumaran, U., Woodard, E.J., Leet, A.I., Rigamonti, D., Sponseller, P.D., Ain, M.C.,
2007. Pedicle and spinal canal parameters of the lower thoracic and lumbar
vertebrae in the achondroplast population. Spine 32, 24232431.
Stanley, G., McLoughlin, S., Beals, R.K., 2002. Observations of the cause of bowlegs
in achondroplasia. Journal of Pediatric Orthopaedics 22, 112116.
Stoll, C., Dott, B., Roth, M.P., Alembik, Y., 1989. Birth prevalence rates of skeletal
dysplasias. Clinical Genetics 35, 8892.
Stuppia, L., Calabrese, G., Gatta, V., Pintor, S., Morizio, E., Fantasia, D., Guanciali
Franchi, P., Rinaldi, M.M., Scarano, G., Concolino, D., Giannotti, A., Petreschi, F.,
Anzellotti, M.T., Pomilio, M., Chiarelli, F., Tumini, S., Palka, G., 2003. SHOX muta-
tions detected by FISH and direct sequencing in patients with short stature.
Journal of Medical Genetics 40, E11.
Suchey, S., Brooks, J.M., 1990. Skeletal age determination based on the os pubis:
a comparison of the Acsdi-Nemeskri and Suchey-Brooks methods. Human
Evolution 5, 227238.
Susanne, C., 1970. Lachondroplasie de la population dage Franc de Coxyde (Bel-
gique). Bulletin de lInstitut Royal des Sciences naturelles de Belgique 46, 178
(in French).
Ubelaker, D.H., 1989. Human skeletal remains. Excavation, analysis, interpretation,
Manuals on Archaeology 2, 2nd ed. Washington Taraxacum, Washington, DC.
Urrutia, V.E., Elizondo, O.R.E., de la Garza, C.O., Guzman, L.S., 2009. Morphometry
of pedicle and vertebral body in a Mexican population by CT and uroscopy.
International Journal of Morphology 27, 12991303.
Vajo, Z., Francomano, C.A., Wilkin, D.J., 2000. The molecular and genetic basis of bro-
blast growth factor 3 disorders: the achondroplasia family of skeletal dysplasias.
Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans.
Endocrine Reviews 21, 2339.
Veselka, B., Hoogland, M.L.P., Waters-Rist, A.L., 2013. Rural rickets: vitamin D
deciency in a post-Medieval farming community from the Netherlands. Inter-
national Journal of Osteoarchaeology, http://dx.doi.org/10.1002/oa.2329.
Walker, B.A., Murdoch, J.L., McKusick, V.A., Langer, L.O., Beals, R.K., 1971. Hypochon-
droplasia. American Journal of Diseases of Children 122, 95104.
Workshop of European Anthropologists (WEA), 1980. Recommendations for age and
sex diagnosis of skeletons. Journal of Human Evolution 9, 517549.
Wynne-Davies, R., Walsh, W.K., Gormley, J., 1981. Achondroplasia and hypochon-
droplasia: clinical variation and spinal stenosis. Journal of Bone and Joint Surgery
- British Volume 63B, 508515.
Young, R.W., 1957. Postnatal growth of the frontal and parietal bones in white males.
American Journal of Physical Anthropology 15, 367386.