Oligodontia and skeletal anomalies in a young boy

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The Case
An 8-year-boy was referred to our skeletal dysplasia center by his dentist for evaluation of possible ectodermal
dysplasia (ED). The dentist noticed small, widely spaced teeth, multiple missing teeth, and the absence of eruption
of secondary teeth. Additionally, the patients body mass index (BMI) had been gradually increasing to the 85th
percentile, thereby classifying him as overweight.
History and physical examination
In addition to the patients presenting tooth anomalies, a review of systems revealed cold intolerance, constipation,
intermittent calf muscle cramps, and occasional dry skin, although he was able to sweat. (The absence of sweating
with risk of overheating is a hallmark of ED.)
On examination, the patient was found to have thin, dark, and fine hair; coarse facial appearance; oligodontia with
widely spaced small teeth; webbed neck; darkening of the skin around his neck (consistent with acanthosis
nigricans); short fingers with excess wrinkles; and diffuse muscular hypertrophy (Figure 1). He was short, 119.2 cm
tall (1.2 percentile for age); weight was 26.4 kg (between 25th and 50th percentile); and BMI was at 85th percentile,
largely because of his relatively short stature.1 Neck palpation noted a bilateral thyroid enlargement of 3 cm by 1
cm. He had attained all developmental milestones anticipated for his age and was doing well at school. There was
no family history of ED, short stature, or other genetic disease. In addition, there was no history of consanguinity.
A skeletal survey showed a delayed bone age of 4 years 6 months at a chronological age of 8 years 9 months, but
no other features of an underlying short stature bone dysplasia were noted, excluding skeletal dysplasia and other
primary disorders as the cause. Also, echocardiogram did not show any evidence of congenital heart disease,
except showing trivial pericardial effusion. Screening laboratory evaluations to investigate the etiology of his short
stature revealed abnormal thyroid stimulating hormone (TSH) at 1302 uIU/mL (normal, 0.5-4.5 uIU/mL) and free T4
<0.1 ng/dL (normal, 0.7-1.8 ng/dL). Additional tests included abnormal thyroglobulin antibody of 108.4 IU/mL (normal
range, less than 20 IU/mL); thyroperoxidase antibody, 654 IU/mL (normal, less than 35 IU/mL); and erythrocyte
sedimentation rate, 17 mm/hr (normal, 0-15 mm/hr).
Differentials

You decide that the patients described and observed symptoms can be attributed to the primary or secondary
causes of short stature (Table). 2,3

Short stature in children can be defined as height that is 2 standard deviations or more below the mean height for
children of comparable sex, chronological age, and ethnicity. Note that these categories are a general guide to the
etiology of poor growth in children and some may overlap or present concurrently. Also note that constitutional
growth delay and familial short stature may be normal variants of short stature.
Constitutional growth delay is a temporary delay in childhood skeletal growth without other physical conditions
causing the delay. This growth delay resolves as the child enters puberty and he or she typically attains an
average height percentile. Familial short stature is characterized by a family history of short stature in an individual
with height below the 3rd percentile despite normal bone age, annual growth rate, and pubertal onset. Primary
growth disorders that are often unresponsive to treatment include chromosomal anomalies, genetic syndromes, and
skeletal dysplasias. Secondary growth disorders are generally amenable to treatment and include endocrine
conditions (eg, hypothyroidism, growth hormone deficiency) and severe congenital anomalies (eg, structural heart
defect) or disease (eg, cystic fibrosis), which divert energy that should have been used for growth.
When approaching a child with short stature, all these diagnostic categories must be considered and prioritized for
further evaluation. Although not all children with short stature will need treatment or benefit from it, some causes are
reversible and effective treatment can have a dramatic influence on overall health and final adult height.
This patient was referred to our clinic for evaluation of ED. Ectodermal dysplasia is a descriptive diagnosis for a

collection of heritable conditions characterized by abnormalities of 2 or more ectodermal structures such as the hair,
teeth, nails, sweat glands, craniofacial structure, digits, and other parts of body. There are X-linked, recessive, and
dominant forms of ectodermal dysplasia.4 Our patient had sparse hair growth, noneruption of secondary teeth, cold
intolerance, and coarse facial features, but normal sweating and no family history of ED.
With further investigation, it became clear that he had symptoms and signs of acquired autoimmune hypothyroidism,
which is a completely reversible condition if treated effectively. Myopathy associated with hypothyroidism classically
presents with proximal weakness, fatigue, exertional pain, slowed movement, diminished deep reexes, stiffness,
and myalgia. Rarely, muscle enlargement is also seen as in this case, and the term Kocher-Debre-Semelaigne
syndrome (KDS) is used.
Growth failure may be an early and major manifestation of hypothyroidism in children, often present for several
years before other symptoms occur. The bone age of a patient with hypothyroidism is typically delayed, thus
allowing for reasonably normal growth potential if supplemented with thyroxine. Abnormal physical features of
hypothyroidism include short stature in conjunction with excessive relative body weight (typically nonlean mass);
puffy faces with a dull expression; bradycardia; delayed deep tendon reflexes; and pseudohypertrophy of the
muscles.
Despite their muscular appearance, children with hypothyroidism may actually be weak. The thyroid gland may be
normal in size, not palpable, or diffusely enlarged. Treatment with thyroid hormone results in prompt improvement in
muscle strength and normalization of serum creatinine kinase concentrations, even in infants with longstanding
congenital hypothyroidism.5,6
A diagnosis of attention-deficit/hyperactivity disorder (ADHD) after successful treatment of hypothyroidism is
described in the medical literature.7 It is thought that the primary hypothyroidism leads to a generalized decreased
activity level that suppresses or masks preexisting ADHD in some children. After thyroid replacement, children with
hypothyroidism have normalization of their overall activity and begin to experience significant behavioral problems
and features of ADHD.
Another explanation for this postthyroid-treatment ADHD diagnosis concerns neurotransmitter imbalance.
Decreased receptor sensitivity to central nervous system catecholamines is accompanied by a compensatory
increase in catechol concentration during hypothyroidism. Rapid normalization after treatment may augment
catechol receptor sensitivity and precipitate a hypercatecholaminergic state.
Diagnosis
Collectively, our patients symptoms and investigations were consistent with autoimmune hypothyroidism. Of note,
newborn screening thyroid results had been normal in 3 samples. A secondary diagnosis of KDS was made, based
on the findings of profound acquired hypothyroidism; diffuse muscle pseudohypertrophy; and features of myxedema,
including short stature, oligodontia, cold intolerance, constipation, dry skin, and coarse facial features.8,9 Clinical
KDS is a myopathy of hypothyroidism associated with pseudohypertrophy in childhood.10
Treatment and response

Our patient was treated with levothyroxine supplementation, 25 mcg/day. His dose was adjusted according to TSH
and free T4 levels to a current euthyroid dose of 100 mcg/day (Figure 2).
Height increased from 119.2 cm (1.2 percentile; z score, -2.237) to 138 cm ( z score, -1.055) over a 2-year time
period. Concurrent with his height increase, his weight percentile dropped from the 50th percentile at presentation to
the 10th percentile, and his BMI dropped from the 85th percentile to between the 25th and 50th percentiles (Figure
3).
Additionally, his hair grew and the texture changed; his generalized muscular hypertrophy faded; and his mildly

coarse facial features softened. There also was prompt eruption of secondary teeth (Figure 4).

After levothyroxine treatment for approximately 6 to 7 months, the patient experienced attention problems and a
decrease in school performance. He was diagnosed with ADHD and treated with Adderall.
Conclusion
Short stature is a general term used for children who are 2 standard deviations or more below the mean height for
children of a particular sex, chronological age, and ethnicity. The diagnosis must be considered in the context of the
childs inherited genetic potential. Hypothyroidism is a treatable cause of short stature in children that may mimic
other genetic conditions such as ED. When evaluating a child with short stature, it is important to assess
longitudinal growth parameters; complete a history and physical exam, including a family history with particular
inquiry of parental height and pubertal timing; and consider normal variants of low growth acquisition (eg, familial
short stature, constitutional growth delay) as well as recognized primary and secondary medical diagnoses.
Not all children with short stature will need treatment or benefit from it. However, some causes are reversible and
effective treatment may allow a child to attain the adult height influenced by midparental height.

Acknowledgement
We wish to acknowledge the Alan and Kathryn Greenberg Center for Skeletal Dysplasias in the McKusick-Nathans
Institute of Genetic Medicine at Johns Hopkins University, Baltimore, Maryland, for supporting this research. We also
would like to acknowledge the patient and his family who graciously allowed us to present his case.

REFERENCES
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2. Rogol AD. Causes of short stature. UpToDate website. http://www.uptodate.com/contents/causes-of-shortstature?source=search_result&search=causes+of+short+stature&selectedTitle=1~150. Updated December 10,
2012. Accessed March 14, 2014.
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upon 13 cases. Aust N Z J Med. 1988;18(6):799-806.
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dysfunction in subclinical hypothyroidism. J Clin Endocrinol Metab. 1997;82(10):3315-3318.
7. Weiss RE, Stein MA, Trommer B, Refetoff S. Attention-deficit hyperactivity disorder and thyroid function. J
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Ms Ghosh is a general physician and graduate of King George's Medical University, Lucknow, Uttar Pradesh, India.
Dr Bjornsson is assistant professor of pediatrics and genetics, McKusick-Nathans Institute of Genetic Medicine and
Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland. Dr Cooke is associate
professor of pediatrics, Division of Pediatric Endocrinology, Johns Hopkins University, Baltimore. The authors have
nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest in
any part of this article. Dr Hoover-Fong, associate professor, Greenberg Center for Skeletal Dysplasias, McKusickNathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, is also a consultant to BioMarin. She
reports that her consultative work has no influence or connection to this article.
Hans Tomas Bjornsson, MD, PhD
David Cooke, MD
Julie Hoover-Fong, MD, PhD, FACMG
Ankita Ghosh, MBBS