A CASE OF APERT SYNDROME IN DIZYGOTIC TWIN: CASE REPORT AND

LITERATURE REVIEW
ABSTRACT
We report a case pf

Introduction
Apert syndrome is a rare genetic disorder form of acrocephalosyndactyly. It is
characterized by craniosynostosis, craniofacial anomalies and sysmmetrical syndactyly of hands
and feet. The early craniosynostosis of the coronal suture, cranial base, and agenesis of the
sagittal suture result in prodromal characteristic of the typical craniofacial characteristic.1
Craniosynostosis developed from autosomal dominant mutation of fibroblast growth factor
receptor 2 (FGFR-2) in cranial suture chondrocytes, which increased cartilage proliferation and
differentiation.2 FGFR2 mutation was common found in male germ line and associated with
paternal age.3
Case Report
A dizygotic male twin was born to a fourth gravida mother at full term by normal vaginal
delivery in Puskesmas. Both parents were in the 3rd decade of life and normal. The second baby
had congenital malformation. The neonate had Apgar scores of 1 and 8 at 1 and 5 minutes,
respectively. His birth weight was 2400 gram, normothermic with respiratory rate of 47 per
minute and heart rate of 136 per minute.
Examination revealed that the baby had very prominent forehead with proptosis eyes, low
set ears and high arched palate. Bilateral syndactyly of four limbs was present.
No family history was reported.

Discussion

Apert (1906) defined a syndrome comprising skull malformation characterized by

acrocephaly of brachysphenocephalic type and syndactyly of the hands and feet
with complete distal fusion with a tendency to fusion of bony structures. The hand,
when all the fingers are webbed, has been compared to a spoon and, when the
thumb is free, to an obstetric hand.
The early craniosynostosis of sutures and spheno-occipital and sphenoethmoidal
synchondrosis result in turribrachycephalic head shape and hypoplastic midface.4 Pharyngeal
attenuation appears to be the consequences of early synostosis of the spheno-occipital
synchondrosis, that precipitates reduction of pharyngeal height. Typical dental characteristic are
crowded and retrusive maxillary arch and maxillary anterior open bite, but has not shown in this
patient. In ocular examination, the typical manifestations are shallow orbits with ocular proptosis
and hypertelorism. Other craniofacial manifestation includes brachycephaly, retruded midface,
and compressed nasal bridge.1,5
Genes associated with skeletal defects may included FGFR1, FGFR2, FGFR3, MSX2, TWIST,
HOXA13, HOXD13. FGFR1 and FGFR2 are co-expressed in prebone and precartilage regions,
which include craniofacial structure.

Heterozygous mutations in the FGFR2 gene (10q26.13) are likely responsible

for this autosomal dominant condition.

Other forms of craniosynostosis in which mutations in FGFR2 have been

found are: Beare-Stevenson Syndrome (123790), Crouzon
Syndrome (123500), Pfeiffer Syndrome (101600), Jackson-Weiss
Syndrome (101200), and Saethre-Chotzen Syndrome (101400).

Sidhu and Deshmukh (1988) reported a somewhat similar case in the child of a first-
cousin couple.

Varying degrees of mental deficiency have been associated with Apert syndrome,
for progressive hydrocephalus, distal esophageal stenosis, cutaneous manifestations
in a series of 136 cases of Apert syndrome (Cohen and Kreiborg, 1993).
Hyperhidrosis was found in all patients. The skin became oily at adolescence and
thereafter, with acniform lesions on the face, chest, back, and upper arms. The
authors commented on and illustrated the phenomenon of 'interrupted eyebrows,'
which may be due to the underlying bony defect. The orbital plate of the frontal
bone is very short, resulting in early fusion of the sphenoparietal suture. This leads
to marked retrusion and elevation of the supraorbital wings, most pronounced
laterally. Interruption of the eyebrows corresponds to this defect. Several patients
had excessive skin wrinkling of the forehead.
Although most cases of Apert syndrome are sporadic, it also follows autosomal
dominant inheritance. Roberts and Hall (1971) observed affected mother and
daughter. Van den Bosch (quoted by Blank, 1960) observed the typical deformity in
mother and son, and Weech (1927) reported mother and daughter. The evidence
strongly suggests autosomal dominant inheritance. Paternal age effect is
demonstrable.
Allanson (1986) described 2 sisters with Apert syndrome, born to normal, unrelated
parents. Germinal mosaicism was proposed.
Rollnick (1988) described what is purportedly the first example of male transmission
of Apert syndrome in affected father and daughter.

the prenatal diagnosis of Apert syndrome by fetoscopy.

Chang et al. (1998) excluded the diagnosis of Apert syndrome in the fetus of an
affected woman with a mutation in the FGFR2 gene

Lomri et al. (1998) analyzed proliferation and differentiation of calvaria cells derived
from Apert syndrome infants and fetuses with FGFR2 mutations. Histologic analysis
revealed premature ossification, increased extent of subperiosteal bone formation,
and alkaline phosphatase-positive preosteoblastic cells in Apert fetal calvaria
compared with age-matched controls. Preosteoblastic calvaria cells isolated from
Apert syndrome infants and fetuses showed normal cell growth in basal conditions
or in response to exogenous FGF2. In contrast, the number of alkaline phosphatase-
positive calvaria cells was 4-fold higher than normal in mutant fetal calvaria cells
with the most frequent Apert mutation, S252W (176943.0010), suggesting increased
maturation rate of cells in the osteoblastic lineage. These and other results showed
that Apert FGFR2 mutations lead to an increase in the number of precursor cells that
enter the osteogenic pathway, leading ultimately to increased subperiosteal bone
matrix formation and premature calvaria ossification during fetal development;
thus, a connection was established between the altered genotype and the cellular
phenotype in craniosynostosis of Apert syndrome.
Miraoui et al. (2010) used microarray analysis to investigate the signaling pathways
that are activated by FGFR2 mutation in Apert craniosynostosis. Transcriptomic
analysis revealed that EGFR (131550) and PDGFR-alpha (173490) expression was
abnormally increased in human Apert calvaria osteoblasts compared with wildtype
cells. Pharmacologic inhibition of EGFR and PDGFR reduced the pathologic
upregulation of phenotypic osteoblast genes and in vitro matrix mineralization in
Apert osteoblasts. Activated FGFR2 enhanced EGFR and PDGFR-alpha mRNA
expression via activation of PKC-alpha (176960)-dependent AP1 (see JUN, 165160)
transcriptional activity. The increased EGFR protein expression in Apert osteoblasts
resulted in part from a posttranscriptional mechanism involving increased Sprouty2
(602466)-Cbl (165360) interaction, leading to Cbl sequestration and reduced EGFR
ubiquitination.
▼Molecular Genetics
In all 40 unrelated patients with Apert syndrome, Wilkie et al. (1995) identified
heterozygosity for 1 of 2 mutations in exon 7 of the FGFR2 gene: S252W
(176943.0010) or P253R (176943.0011). The findings confirmed that Apert syndrome
is allelic to Crouzon syndrome.
In a patient with Apert syndrome, Oldridge et al. (1997) identified a noncanonical
mutation in exon 7 of the FGFR2 gene (S252F; 176943.0017).
In a series of 260 cases of Apert syndrome, Oldridge et al. (1999) found that 172
carried the S252W mutation and 85 had the P253R mutation, indicating that the
molecular mechanism of Apert syndrome is exquisitely specific. Two patients had
an Alu-element insertion in or near exon 9 (176943.0025).
Lajeunie et al. (1999) identified the S252W and P253R mutations in 23 (64%) and 12
(33%) of 36 Apert syndrome patients, respectively. One affected fetus had the S252F
mutation.
Moloney et al. (1996) found that 74 of 118 patients with Apert syndrome had the
FGFR2 S252W mutation and 44 had the P253R mutation. Using sequence analysis of
the neighboring introns flanking the mutation-prone exon and a novel PCR-based
assay, ARMS (amplification refractory mutation system), to determine the phase of
the mutant allele and nearby polymorphisms in 57 informative families, Moloney et
al. (1996) determined that the mutant allele was paternal in origin in all cases. The
authors noted that a paternal bias for point mutations is evident in a number of
disorders, but that the extreme skewing in favor of paternal mutations observed in
Apert syndrome is unusual. A paternal age effect was noted. The data suggested a
stronger paternal age effect for the S252W mutation, which involves a CpG
dinucleotide, than for the P253R mutation, which does not.
Glaser et al. (2003) used allele-specific peptide nucleic acid PCR assays to determine
FGFR2 mutation frequency in the sperm of 148 men aged 21 to 80 years. The number
of sperm with FGFR2 mutations increased in the oldest age groups among men who
did not have a child with Apert syndrome. These older men were also more likely to
have both mutations in their sperm. However, this age-related increase in mutation
frequency was not sufficient to explain the Apert syndrome birth frequency. In
contrast, the mutation frequency observed in men who were younger and had
children with Apert syndrome was significantly greater, suggesting selection for
sperm with specific mutations. Glaser et al. (2003) concluded that contributing
factors to the paternal age effect may include selection and a higher number of
mutant sperm in a subset of men ascertained because they had a child with Apert
syndrome. No age-related increase in the frequency of these mutations was
observed in leukocytes. Selection and/or quality control mechanisms, including
DNA repair and apoptosis, may contribute to the cell type differences in mutation
frequency.

▼Genotype/Phenotype Correlations
Park et al. (1995) reported 36 patients with Apert syndrome, 35 of whom were found
to carry either the S252W or P253R mutation in the FGFR2 gene, with a frequency of
71% and 26% for these 2 mutations, respectively. A study of 29 different clinical
features demonstrated no statistically significant differences between the 2
subgroups defined by the 2 major mutations.
Slaney et al. (1996) found differential effects of the 2 FGFR2 mutations on syndactyly
and cleft palate in Apert syndrome. Among 70 unrelated patients with Apert
syndrome, 45 had the S252W mutation and 25 had the P253R mutation. The
syndactyly in both the hands and the feet was more severe in patients with the
P253R mutation. In contrast, cleft palate was significantly more common in patients
with the S252W mutation. No convincing differences were found in the prevalence
of other malformations associated with Apert syndrome.
Lajeunie et al. (1999) found considerable clinical variability among 36 patients with
Apert syndrome confirmed by genetic analysis. Two patients had no clinical or
radiologic evidence of craniosynostosis. In 2 other patients with atypical forms of
syndactyly and cranial abnormalities, the detection of a specific mutation was
helpful in making the diagnosis.
Among 21 Apert syndrome patients who underwent craniofacial surgery, von
Gernet et al. (2000)found that the postsurgical craniofacial appearance was better in
patients with the P253R mutation, whereas these patients showed a more
pronounced severity of the syndactyly. Six patients had the P253R mutation and 15
had the S252W mutation.

▼Cytogenetics

Dodson et al. (1970) described deletion-translocation of the short arm of a

chromosome 2 to the long arm of a chromosome 11 or 12 in a patient with Apert
syndrome. They found reports of chromosomal abnormalities in 3 other cases of
Apert syndrome.

▼Population Genetics
Blank (1960) estimated the frequency of Apert syndrome to be 1 in 160,000 births.
Cohen et al. (1992) studied the birth prevalence of Apert syndrome in Denmark,
Italy, Spain, and 4 areas of the United States. A total of 57 cases gave a birth
prevalence calculated to be approximately 15.5 per million births, which is twice the
rate determined in earlier studies. The mutation rate was calculated to be 7.8 x 10(-6)
per gene per generation. Apert syndrome accounted for about 4.5% of all cases of
craniosynostosis. Czeizel et al. (1993) reported a validated birth prevalence of Apert
syndrome in Hungary to be 9.9 per million live births. The mutation rate was
calculated to be 4.6 x 10(-5) per gene per generation. Data on 14 other 'sentinel'
anomalies observed between 1980 and 1989 were given.
Tolarova et al. (1997) reported that the California Birth Defects Monitoring Program,
from 1983 through 1993, identified 33 infants with Apert syndrome. The sample was
enlarged with an additional 22 cases from the Center for Craniofacial Anomalies at
the University of California, San Francisco. Birth prevalence calculated from the 31
cases was 12.4 per million live births. The calculated mutation rate was 6.2 x 10(-6)
per gene per generation. Asians had the highest prevalence (22.3 per million live
births) and Hispanics the lowest (7.6 per million). In a population-based subsample
of 31 affected infants, there was an almost equal number of affected males and
females, but in the San Francisco sample there were more affected females (sex ratio
0.79). For all cases, the mean age of mothers was 28.9 years, and of fathers 34.1 years.
Almost half of the fathers were older than 35 years when the child was born; for
more than 20% of cases, both parents were older than 35 years.
The rarity of syndromic craniosynostosis makes
any estimates speculative, particularly when combined
with twinning. In Crouzon’s and Apert’s syndromes,
an occurrence of 1.5 per 100,000 births
(0.000015) merged with twinning rates of 2.5% would
create the rare occurrence of 3 per 10,000,000 births.
Such a low occurrence rate accounts for the few case
reports of twins with syndromic craniosynostosis.
The responsible gene has been mapped to 10q26. The defect causes abnormal osseous
development resulting in irregular bridging of the mesenchymal tissue that eventually forms
bone. The cranium and distal extremities are predominantly affected.
Autosomal dominant. Increased paternal age is considered a risk factor.
children with Apert syndrome tend to have greater-than-normal intracranial
volume.28
Syndromic craniosynostosis occurs in between 1
per 10,000 live births (Muenke’s syndrome) to 1 per 80,000 live
births (Apert’s syndrome). Because of the these low occurrences,
the actual incidence of twinning in syndromic craniosynostosis
is difficult to predict. A theoretical incidence between 2.5 per million
live births in Muenke’s syndrome and 2.5 per 8 million live
births in Apert’s syndrome can be estimated.

SYNDROMIC CRANIOSYNOSTOSIS
Incidence
In contrast to isolated craniosynostoses, syndromic
craniosynostosis typically occurs in association with
various other structural anomalies. The incidence of
Crouzon’s and Apert’s syndromes is approximately
15.5 per 1 million live births, with each accounting
for approximately 4.5% of all cases of craniosynostoses.
19,20 The occurrence of Muenke’s syndrome (often
confused with Crouzon’s syndrome) is much more
common at 0.8 to 1 per 10,000 live births.21
Etiology
Mutations in fibroblast growth factor receptor genes,
tyrosine kinases that are essential for intracellular signaling,
have been pinpointed as the cause of many
cases of syndromic craniosynostosis.7 Fibroblast
growth factor receptor 2 mutations are most commonly
responsible for many craniosynostosis syndromes,
including Apert’s, Crouzon’s, and Pfeiffer’s
syndromes, and are inherited in autosomal dominant
fashion. Muenke’s syndrome is the result of a
Pro250Arg mutation in the fibroblast growth factor
receptor 3 gene and is also inherited in an autosomal
dominant fashion. Mutations in TWIST genes have
been associated with a Saethre-Chotzen syndrome,
and homeobox mutations have been associated with
Boston-type craniosynostosis.
Twinning
The actual incidence of twinning in patients with syndromic
craniosynostosis has not been defined
because of its rarity. Only a couple of articles describe
twinning in syndromic craniosynostosis, both of
which involved patients with Crouzon’s syndrome.
22,23 There have not been enough reported
cases to determine whether one suture is more involved
more frequently than others (Fig 3).

dominant autosomes, mutations from 10Q26 chromosome FGFR2, including Ser252Trp

and Pro253Arg mutations.
- The average occurrence of bikoronal sinostosis with hypertelorism or exorbitism.
- Strabismus
- proptosis, maxillary hypoplasia, mandibular prognathism (Panigrahi I, 2011)
- large ear lobes
- syndacty of the whole finger (mitten hand) and toes and varied mental retardation.
Angka kejadian pada
pasien sindrom Apert dan sindrom Crouzom
hampir sama dengan perbandingan sex ratio
0,79 dari 53 pasien yang lebih banyak pada
pasien perempuan (Kniffin CL, 2013).
Distribusi pasien yang didapatkan
sebanyak 29% terdiagnosa dengan sindrom
Crouzon, 54% terdiagnosa sebagai sindrom
Apert, dan 17% terdiagnosa sebagai sindrom
Pfeiffer. Penelitian Di Rocco (2009),
menyebutkan distribusi kelainan tersebut
diatas sebanyak 28% terdiagnosa dengan
sindrom Crouzon, 22% terdiagnosa sebagai
sindrom Apert, dan 20% terdiagnosa sebagai
sindrom Pfeiffer. Terdapat perbedaan yang
mungkin disebabkan masih sulitnya
mendiagnosa pasien kraniosinostosis
sindromik di Indonesia.
Profil pasien kraniosinostosis
sindromik selama 5 tahun di RSUD Dr.
Soetono Surabaya, menunjukkan distribusi
pasien sebanyak 29% terdiagnosa dengan
sindrom Crouzon, 54% terdiagnosa sebagai
sindrom Apert, dan 17% terdiagnosa sebagai
sindrom Pfeiffer. Kelainan kraniosinostosis
sindromik di RSUD Dr. Soetomo dijumpai
tersering pada perempuan serta sindroma
apert. Dimana usia tersering saat datang ialah
5-10 tahun, diakibatkan oleh terlambatnya
diagnosis kelainan tersebut.

Based on this research, patient patients who came with syndromic craniosinostosis
included 3 diagnoses of disease; namely Apert syndrome, Crouzon syndrome, and Pfeiffer
syndrome. From the results of the study obtained a total of 24 patients,
which can actually be extracted from these results is whether there is a hereditary factor of
the patient's parents. This is because the incidence rate of Apert and Crouzon syndrome is
a more common and autosomal dominantly derived syndrome, where mutations occur
from fibroblast growth factor receptor 2 (FGFR2) (Pournima G et al, 2011). In addition it
can also be tracked regarding maternal age at delivery, and the father's age at fertilization
will increase the risk of gene mutation in FGFR2 (Wilkie AO, 2005).
Based on the gender, the results of the percentage of male patients 54% (13 patients) and
female 46% (11 patients) of men more than women have not found a source that explains in
detail about the prevalence of syndromic craniosinostosis in gender, because from several
journals obtained amount patients by gender vary. The incidence rate in patients with
Apert syndrome and Crouzom syndrome is almost the same as the sex ratio ratio of 0.79
out of 53 patients who are more likely in female patients (Kniffin CL, 2013).
The division of the above patients by age is divided into ages <1 year,> 1 year - 2 years, 3
years - 5 years, 6 years - 10 years,> 10 years, and> 20 years. The basis of this division is
done to facilitate the distribution of patients based on age. Early diagnosis of
craniosinostosis is very important, delayed referral may result in the risk of complications
and unsatisfactory outcomes (Chatterjee, 2009).
Chatterjee also mentioned that the abnormality is one-third recognized at birth, with an
average age of 3.1 months. In this study, the entire patient checked first at the age of 5-10
years. This may be due to delays in diagnosis in smaller units such as puskesmas, as well as
local hospitals, so patients tend to arrive late. Based on Pagnoni (2013) age at first arrival
of the patient for self-examination may be helpful for patient management planning. At <6
months of age, operative measures are performed in patients with syndromic
craniosinostosis in order to avoid morbidity rates due to the growing growth of cranium
according to the child's age, and to minimize invasive surgery in patients.

The risk of having a baby with birth defects – usually heart or nervous system
problems which can sometimes be fatal – is still small, but it rises from 3% in the
general Pakistani population to 6% among those married to blood relatives. The
researchers also found a doubling of the risk in the babies of white British women
who were over the age of 34. That increased risk, rising from 2% to 4%, is already
known.

There is no cure for Apert syndrome, but early clinical diagnosis, prompt supportive
treatment and timely referral to multidisciplinary centre can offer these children a chance of
obtaining a more normal facial appearance and the opportunity to grow, develop, and
integrate socially with their peers. Discovery of mutation in FGFR genes now allows the
definitive antenatal diagnosis of Apert syndrome and other craniosynostosis syndromes and
skeletal dysplasia. This will allow for appropriate family counseling and perhaps, in the
future, gene therapy for the correction of the mutation.

The etiology is unclear but various theories have been proposed [4-6]. The most favoured theory is still
based on that originally proposed by Virchow in 1856 which describes intrinsic abnormality of the
sutures resulting in fusion and a reduction in growth perpendicular to the plane of the suture1. Inherited
in an autosomal dominant fashion, most cases arise as spontaneous mutations that appear to originate
almost exclusively in the paternal germ line. Two mutations on chromosome10q, found in adjacent
codons leading to altered structure in the fibroblast growth factor receptor (FGFR 2) have been
identified as being responsible for the defects seen in Apert syndrome. Almost 80% of the cases of
crainiosynostosis arise sporadically rather than being associated with syndromes. The two most
common of the syndromic craniosynostoses, collectively known as acrocephalosyndactyly, are Crouzon’s
and Apert, which together make up 70% of such cases [7]. Apert syndrome has distinctive clinical
features. The coronal suture fuses prematurely (at less than 3 months), leading to an acrocephalic (cone-
shaped) head with shortened antero-posterior diameter, and a high prominent forehead [8-11]. In our
case, in addition to the coronal suture, the sagittal, lambdoid and metopic sutures were also fused. This
is a unique feature in our case, as it has not been reported previously. Brachycephaly, hypertelorism,
midface hypoplasia occurs. There is prominence of the mandible with resultant malocclusion. These
features were present in our case. A high arched palate and cleft palate (30%) is a feature [1]. Our case
had a high arched palate, however there was no associated cleft. The digital manifestations include
distal (acro-) fusion (syndactyly) of commonly the second to fourth digits of the hands. These findings
are frequently symmetrical. The thumb may be incorporated into the mid-hand syndactyly as seen in
our patient. Progressive longitudinal fusions also occur (symphalangism). Fusion of bodies of C5 and C6
are seen in our patient, a common feature noted in 70% of the cases [1]. There are associated cardiac
and genitourinary abnormalities in 10% of patients. Ventriculomegaly and abnormalities of the corpus
callosum and septum pellucidum are not uncommon. Examination did not reveal any cardiac or
genitourinary abnormalities. MRI showed ventriculomegaly with agenesis of corpus callosum, absent
septum pellucidum, vertical hippocampi and a high riding third ventricle. Previous studies reported
affected individuals with anomalies of viscera, elbows and shoulders, skeleton and central nervous
system with impaired mental function [10, 12]. There were no anomalies of the viscera, elbows or
shoulders. Apert syndrome is a rare disorder, however it should be recognized early, as neonatal
diagnosis Apert syndrome is a rare disorder, however it should be recognized early, as neonatal
diagnosis can be attempted via genetic workup on the basis of suspicious sonographic findings. Mothers
may be offered genetic counseling during pregnancy. Many surgical treatment options can produce
better outcome if performed early. Craniotomy within the first year of life has been found to result in
higher adult intelligence levels, with 50% of such patients having an IQ ≥70, as compared with only 7% of
those patients in whom such a procedure is performed later in life [15].

CASE REPORT APERT SYNDROME

Identity

Name: By. Rafi

Age: <1 day

Male gender

Mother's Name: Nurianim

Age: 35 years

Father's name: Suriadi

Age: 40 years
Labor: Spontaneous

Date of Birth: November 15, 2017 14:05 WITA

Pregnancy Age: 41-42 weeks

Anamnesis

Patient born from G4P3A0 mother with 41-42 weeks' gestation. The patient's mother controls 2x during
pregnancy at the Puskesmas and does not get an ultrasound so no twins can be detected.

Physical examination

Awareness: CM; crying fast, actively moving

Anthropometry:

- Weight: 2400 gr

- Body length: 50 cm

- Head circumference: 35 cm

- Chest circumference: 30 cm

- Abdominal circumference:? cm

- Arm circumference: 10 cm

Vital sign

APGAR SCORE 1 '= 3 3' = 5 5 '= 8

Heart Rate: 136 times per minute

RR: 47 times per minute

S: 36.5OC

Statu Generalis

Head:

prominent forehead (+), caput (-), molding (-), laceration (-),

Eyes: The conjunctiva is not anemic, the sclera is not jaundiced, hypertelorism, proptosis

Nose: nasal flaring (-), flat nasal (-)

Ear: normal shape, low set ear, secret (-)

Mouth: perioral cyanosis (-), high and intact ceilings, macroglossi (-), teeth have not erupted

Neck: supra sternal retraction (-)

Thorax

Inspection: symmetrical shape and motion, pigeon chest (-), funnel chest (-), retraction (-)

Lung: Bronkovesicular sound left = right, wh - / -, rh - / -

Heart: Ictus cordis not visible, BJ S1 S2 regular, murmur (-)

Abdomen

Inspection: Convex, soft, epigastric retraction (-)

Askultation: Normal bowel sounds

Palpation: palpable liver 2 cm bac right

lien palpable 1 cm bac left

Genital and Anus

Male, scrotum ruggae (+), testis (+)

Atresia ani (-)

Extremities

Akral warm, CRT <3 ", syndactyly, webbing foot

Neurological Examination

• Movement: On

• Moro Reflex (+)

• Rooting refresh (+)

• Suckling reflex (+)

• Plantar grasp reflex: can not be assessed for being syndactyly

Management

- Vit K 1 mg, anterolateral left thigh

- Oxytetrasiklin zalf eyes

- ASI ad lib

References
1. Rynearson D. Case Report: Orthodontic and Dentofacial Orthopaedic Consideration in
Apert’s Syndrome. Angle Orthod 2000;70:247-252.
2. Chen P, Zhang L, Weng T, Zhang S, Sun S, et al. A Ser252Trp Mutation in Fibroblast
Growth Factor Receptor 2 (FGFR2) Mimicking Human Apert Syndrome Reveals an
Essential Role for FGF Signaling Regulation of Endochondral Bone Formation. PLOS
ONE 2014; 9(1):e87311.
3. Goriely A, McVean GA, Rojmyr M, Ingemarsson B, Wilkie AO. Evidence selective
advantage of pathogenic FGFR2 mutation in the male germ line. Science 2003;
73(4):939-47.
4. Khan S, Chatra L, Shenai P, Veena KM. Apert Syndrome : A Case Report. Int J Clin
Pediatr Dent 2012; 5(3):203-206.
5. Madhura D, Naresh S. Apert’s syndrome: A rare case report. J Indian Acad Oral Med
Radiol. 2010; 22: 232-235.

6. Craniosynostosis Anomalies
7. in Twins
8. John A. van Aalst, MD, Geoff Schultz, BS,
9. Barry L. Eppley, MD, DMD THE JOURNAL OF CRANIOFACIAL SURGERY / VOLUME 16, NUMBER 4 July 2005 696-
698