|Year : 2021 | Volume
| Issue : 3 | Page : 208-212
Apert's syndrome: A rare congenital disorder
Rajib Sikdar, Khooshbu Gayen, Supreet Shirolkar, Anisha Bag, Santanu Mukhopadhyay, Subir Sarkar
Department of Pedodontics and Preventive Dentistry, Dr. R Ahmed Dental College and Hospital, Kolkata, West Bengal, India
|Date of Submission||15-May-2021|
|Date of Acceptance||25-Jun-2021|
|Date of Web Publication||23-Aug-2021|
Department of Pedodontics and Preventive Dentistry, 2C, Dr. R. Ahmed Dental College and Hospital, Kolkata - 700 014, West Bengal
Source of Support: None, Conflict of Interest: None
Apert's syndrome (acrocephalosyndactyly) is a developmental malformation characterized by craniosynostosis, syndactyly, and dysmorphic facial features. The purpose of this paper is to report a case of an 8-year-old child affected with Apert's syndrome with emphasis on the craniofacial and oral features. It demonstrates autosomal dominant inheritance and occurs due to point mutation of fibroblast growth factor receptor-2 gene in chromosome 10q25 and 10q26. The patient presented with brachydactyly, syndactyly, polydactyly, hypoplastic maxilla, and malalignment of teeth. The cases of Apert's syndrome can only be treated by multidisciplinary approach. Early diagnosis and proper counseling of families can help in better management.
Keywords: Acrocephalosyndactyly, Apert's syndrome craniosynostosis, polydactyly
|How to cite this article:|
Sikdar R, Gayen K, Shirolkar S, Bag A, Mukhopadhyay S, Sarkar S. Apert's syndrome: A rare congenital disorder. J Dent Res Rev 2021;8:208-12
|How to cite this URL:|
Sikdar R, Gayen K, Shirolkar S, Bag A, Mukhopadhyay S, Sarkar S. Apert's syndrome: A rare congenital disorder. J Dent Res Rev [serial online] 2021 [cited 2021 Dec 4];8:208-12. Available from: https://www.jdrr.org/text.asp?2021/8/3/208/324422
| Introduction|| |
Apert's syndrome is a rare congenital malformation mainly involved head-and-neck region and limbs. “Craniosynostosis” is a term that means premature fusion of one or more sutures of the skull (commonly coronal and/or sagittal), resulting in asymmetrical skull growth and deformities of skull vault and/or base. Many craniosynostosis syndromes share some common features such as synostosis, facial and limb abnormalities. Among them, Apert's syndrome is a rare autosomal dominant disorder first described by Wheaton in 1894. Later, series of nine cases with similar features was described by Eugene Apert in 1906.
Apert's syndrome is a rare acrocephalosyndactyly type of syndrome with a 9.9–15.5/1,000,000 live births incidence rate worldwide. It constitutes 4% of all craniosynostosis cases. Apert's syndrome rarely seen in India.
Prodromal characteristics of Apert's syndrome are:
- Early fusion of coronal sutures, cranial base, and agenesis of sagittal suture (sometimes)
- Midface hypoplasia
- Syndactyly of hands and feet.
This syndrome rarely shows central nervous system (CNS), gastrointestinal tract (GIT), and urogenital or verbal anomalies. Some patients may complaint of recurrent upper respiratory tract infection, sleep apnea, and snoring.
Apert's syndrome occurs due to point mutation of the fibroblast growth factor receptor (FGFR-2) gene in chromosome 10q25 and 10q26. There is no sexual predilection reported but more prevalent in certain areas such as highest in Asians and lowest number of cases seen in the Hispanic population.
| Case Report|| |
An 8-year-old child reported to the department of pedodontics and preventive dentistry with a chief complaint of malalignment of teeth. The patient also had some carious teeth with a complaint of occasional pain.
On extraoral examination, some significant features pointing toward Apert's syndrome. On examination of upper limbs, there was the presence of brachydactyly, and in the lower limbs, syndactyly and polydactyly were present [Figure 1]. Measurement of lower limbs showed discrepancy in length between two limbs resulted in slightly slanted posture [Figure 2]. Furthermore, evidence of bilateral camptodactyly (curling of foot inwards with toes pointing down) was present.
|Figure 1: (a) Photograph showing brachydactyly in the upper limbs, (b) photograph showing syndactyly with complete fusion of second, third, fourth, and fifth toes and polydactyly in lower limbs|
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|Figure 2: Photograph showing slightly slanted posture due to length discrepancy between two limbs|
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The extraoral examination revealed macrotia, frontal bossing, depressed and broad nasal bridge, depressed maxillary and zygomatic bone, hypertelorism, and aerocephaly [Figure 3]. Head circumference measurement was 51 cm and the height of the child was 121 cm.
|Figure 3: (a-c) Extraoral photograph showing frontal bossing, macrotia, depressed, and broad nasal bridge|
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Intraoral examination displayed missing 52 and 62 and broken crown of 51. Further, examination revealed carious 55, 65, 75, 84, and 85. 16 and 26 were erupting with the presence of crowding. Frenulum examination showed normal frenulum attachment [Figure 4].
|Figure 4: (a) Vestibular view, (b) intraoral maxillary view showing bulbous alveolar ridge, (c) Intraoral mandibular view showing enlarged tongue, (d) Normal frenulum attachment|
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Radiographic examination of orthopantomogram (OPG) and lateral cephalogram was taken further to confirm the presence of hypoplastic maxilla and zygomatic bone with normally developing mandible, resulting in concave facial pattern with Class III tendency. OPG revealed severe space crunch in maxilla indicating probable crowding in the upper arch and mild arch size tooth length discrepancy in mandible, resulting in lower anterior crowding and rotation in addition with a lack of root formation in the upper and lower premolar and canine teeth which may be indicating retarded skeletal growth and lower dental age [Figure 5].
|Figure 5: (a) Lateral cephalograph showing hypoplastic maxilla and zygomatic bone with concave facial pattern (b) orthopantomogram showing severe crowding due to space crunch in both arches|
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Upon enquiring about pregnancy history, it was found that child born from a nonconsanguineous marriage but late parental age with normal delivery and without any medical complication. There was no history of any other family members with these kinds of features. The child had a computed tomography scan at 1-year age and magnetic resonance imaging (MRI) at 3 years age which shows normal brain function. An echocardiography done at 1 year of age also shows no cardiac abnormalities. However, further inquiries about the medical history revealed the history of febrile convulsion at 4 years of age and an electroencephalogram report of 3 years of age concluded the presence of generalized cerebral dysrhythmia. This child also had a complaint of recurrent low-grade fever throughout his childhood.
Chromosomal analysis revealed normal male karyotype with no numerical or structural chromosomal anomalies at 450–550 banding resolution.
| Discussion|| |
Apert's syndrome is a craniosynostosis type of syndrome affecting the development of skull and limbs. It is also described as a branchial arch syndrome because it mainly affects the 1st branchial arch derivatives. Apert's syndrome is a form of acrocephalosyndactyly (Type I) syndrome, summarizes its prodromal characteristics such as acrocephaly or cone-shaped calvarium, and syndactyly or fusion of phalanges of hands and feet. Along with this features, many other significant craniofacial and oral characteristics can be seen in Apert's syndrome. Main features of Apert's syndrome are listed in [Table 1].
Some other features such as recurrent upper respiratory tract infection and ear infection, heavy sweating (Hyperhidrosis), severe acne, patches of missing ear in eyebrows, fusion of spinal bone in the neck, cleft palate, sleep apnea, and snoring less frequently seen. Rarely, symptoms of CNS, GIT, urogenital, and verbal anomalies are reported. Mental disorder is rare, but mild-to-moderate intellectual deficiency may be seen. No vertebral anomalies associated with this syndrome.
Apert's syndrome is genetic disorder of autosomal dominant inheritance. There are four types of FGFR gene (FGFR1-4). It is developed due to point mutation of FGFR-2gene on chromosome 10q25 and 10q26. Two specific amino acid mutations (either S252W or P253R substitutions) occur in the binding site between immunoglobulin-like loop 2 and immunoglobulin-like loop 3. Point mutation occurs either in ser252Trp or Pro253Arg in FGFR-2. FGFR gene codes a specific protein for FGFR which has many important roles in developmental stages of child. Any mutation or change in this gene can be results in many developmental discrepancies, like:
- Embryogenesis and it's deficiency
- Premature gastrulation
- Implantation anomalies
- Impairment of epithelial mesenchymal interaction
- Defect in membranous and endochondral bone formation.
Fibroblast growth factor (FGF) responsible for formation of blood vessels, wound healing, embryonic evolution and regulation of cellular division, and growth and maturation. FGF is also an important role in signal pathways which function in fusion of skull bones. That's why any defect in FGF signaling pathway or mutation of gene results in acrocephaly or cone-shaped calvarium formation. Many features of Apert's syndrome may be due to abnormal migration of in early embryonic stage. The FGFR2 gene is expressed in the metaphysis, diaphysis, and interdigital mesenchymal area of the phalanges. Hence, any mutation of FGFR-2 gene alters protein and signaling pathway results in prolonged signaling which cause premature fusion of fingers of hands and feet or syndactyly. This explains two main characteristics of acrocephalosyndactyly or Apert's syndrome.
One of the main characteristics of Apert's syndrome is Apert's hand and feet. Apert's hand is of three types: (a) spade (index, middle, and ring finger fused); (b) mitten (thumb also fused with index finger); (c) rosebud (all digits are fused). According to Baluth and Von Torne Apert's foot is also of three types: (a) Type I (toes II–IV webbed together), Type II (toes II–V fused together), and Types III (all toes fused together). In this case, we can see Type III syndactyly in right foot and Type II in the left.
Apert's syndrome has an incidence rate of 9.9–15.5/1,000,000 live births and 4% of all craniosynostosis cases reported worldwide. It has no sexual predilection. Patients usually had normal karyotype as it is seen in this case chromosomal analysis of 450–550 banding resolution. There is some evidence that suggests though it can be inherited from any of the parents either from already affected parent or as a fresh mutation, but it usually the mutation occurred in the sperm. Hence, Apert's syndrome generally linked with older fathers as it is seen in this case.
Along with Apert's syndrome, other symptoms such as Crouzon syndrome, Carpenter syndrome, Chotzen syndrome, and Pfeiffer syndrome also comes under this group of craniosynostosis syndrome. Correlation of the above syndromes with Apert's syndrome is listed in [Table 2].
|Table 2: Correlation of the clinical findings of Apert syndrome with Crouzon syndrome, carpenter syndrome, Pfeiffer syndrome, and Chotzen syndrome|
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There is no cure for Apert's syndrome as it are congenital anomalies, so it can only be prevented by early diagnosis before birth. Parental tridimensional sonography and MRI at midtrimester are the investigation of choice. However, detection of mutation of FGFR-2 gene is definitive.
The cases of Apert's syndrome can only be treated by multidisciplinary approach. A surgical team of neurologist, craniofacial surgeon, pediatric surgeon, pediatric anesthetist, plastic surgeon, pedodontist, and orthodontist is required.
| Conclusion|| |
Apert's syndrome (acrocephalosyndactyly) is a congenital disorder due to mutation of FGFR-2 gene results in carniofacial and limb anomalies. As it is a congenial disorder, prevention by early diagnosis is the best treatment modality. This case report hope to refining the knowledge about Apert's syndrome among the health-care professional and also aims to help in counseling of families and proper treatment planning for the child.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]