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Apert Syndrome in Lagos – a Case Report and Literature Review * Balogun Modupe, Balogun Bolanle, Adekoya Bola and Popoola Ruqayat. Nigerian Medical Practitioner Vol. 63 No 1-2, 2013 (21 - 25 )

Summary Apert Syndrome is a rare autosomal dominant disorder characterized by premature fusion of sutures of bones of the skull (Craniosynostosis), fingers and toes (Syndactyly) to different degree. Though it is rare, it is pertinent for clinicians to know about this condition so as to improve their ability to manage it and to note that management is multidisciplinary. We present a case of Apert Syndrome in a one month old Nigerian female, and one of a set of twins that presented with proptosis, hypertelorism, high arched palate and fusion of bones of fingers and toes.

Keyword: Apert syndrome, craniosynostosis, proptosis, hypertelorism

Introduction Apert syndrome is a rare autosomal dominant disorder,(1,2)due to mutations in the Fibroblast Growth Factor Receptor2 ( FGFR2) gene . It is characterized by premature fusion of sutures of bones of the skull (craniosynostosis) which can cause limitation of brain growth, raised intracranial pressure leading to visual impairment, sleep impairment and impairment in mental development. The premature fusion of sutures of bones of the skull also affects the shape of the head and face. There is fusion or severe webbing of fingers and toes to different degree (syndactyly).(2,4) It is a form of Acrocephalosyndactyly. The syndrome was mentioned as early as 1842 by Baumgartner(5)and also described by Wheaton in 1894,(6,7)but was not given a name until 1906 when a French paediatrician; Eugene Apert reported nine cases and since then, his name has been associated with it. It accounts for about 4.5% of all cases of craniosynostosis. Prevalence is estimated at 1:65,000 (approximately 15.5 in 1,000,000) live births (8) with limited study done worldwide. It is known that Asians have the highest prevalence (22.3 cases per million live births) and Hispanics have the lowest prevalence (7.6 cases per * Department of Ophthalmology Lagos State University Teaching Hospital / College of Medicine 1-5 Oba Akinjobi Street, Ikeja. Lagos-Nigeria

million live births).(9)It has no sex predilection and can be detected prenatally by ultrasound or in newborn.(10) Search of literature revealed limited report on Apert Syndrome in Nigeria. Ofodile F.A in Ibadan in 1982 reported a case of Acrocephalosyndactyly with Hydrocephalus and dextrocardia in a Nigerian child.(11) This article is aimed at reporting a case of Apert Syndrome seen at our centre. Though the condition is well known, it is rare in our environment and a good knowledge of the syndrome will help in the management which is multidisciplinary. Case Report A one month old female patient was seen in the eye clinic with the complaint of protrusion of both eyes since birth. The informant was the mother. The patient was one of a set of twins from a monogamous family. Father was 29year old Security officer while mother was 24year old housewife. Pregnancy was carried to term but mother claimed she had febrile illness at 5months gestation which lasted for about 4 days and was treated in a hospital. Ante-natal clinic was at a private hospital but mother confirmed use of native herbs and orthodox medications. Delivery was by aesarean section at 42weeks due to abnormal lie of one of the children and child was said not to have cried immediately. There was no similar malformation in

* Correspondence Author

Nigerian Medical Practitioner Vol. 63 No 1-2, 2013

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Apert Syndrome in Lagos

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other sibling (2 twin) or other members of the family. Examination revealed an active baby, afebrile, not pale, anicteric and not in obvious distress. There was high arched palate but no cleft. She had a head circumference of 41.5cm, chubby cheeks and a flat nose. Assessment of visual acuity was with a

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There was fusion of 2 , 3 , and 4 fingers with dimple on the dorsum of the hands and fusion of the toes with inward deviation of the feet (Figures 3 and 4). There was no polydactaly. The mother was advised to tape the eyelids of the child at sleep in view of the lago phthalmus and child was placed on antibiotic ointment.

Figure 1. Photograph of patient showing proptosis and lid retraction. (Side-view)

Figure 2. Photograph of patient showing proptosis, lid retraction, hypertelorism and flat nose.

pen-torch and patient was able to blink to bright light. There was proptosis of both eyes with retraction of upper and lower lids, lagophthalmus and brownish discolouration of conjunctivae in both eyes and hypertelorism. (Figures 1& 2). The corneas, anterior chambers, lens and fundi in both eyes were normal.

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Parents were counselled that the chances of having another child with Apert syndome is almost non-existence as both parents do not have the syndrome. But the child has a 50% chance of passing the condition to an offspring. Management of child was in conjun ction with neurosurgeons and plastic surgeons. As at the time of reporting this case patient was yet to have any surgical intervention.


Balogun Modupe et al

Figure 3. Photograph of patient showing syndactyly of fingers and dimple on dorsum of the hand.

Figure 4. Photograph of patient showing syndactyly of the toes.

Discussion Apert syndrome is a genetic disorder characterized by the premature fusion of certain skull bones (craniosynostosis) and fusion of a varied number of fingers and toes (syndactyly). It is thought to be due to mutations in the gene called Fibroblast Growth Factor Receptor2(FGFR2). Among its multiple functions, this protein signals immature cells to become bone cells during embryonic development. Also during development, the hands and feet have selective cells that die, a

process known as selective cell death or apoptosis causing separation of the digits. In the case of acrocephalosyndactyly this does not occur thus skin and rarely bones, between the fingers and toes fuse.(12) Also, a mutation in a specific part of the FGFR2 gene alters the protein causing prolonged signalling which can promote the premature fusion of bones in the skull, hands and feet(2). The syndrome may be inherited in an autosomal dominant fashion(2)and a person with the condition has a 50% chance of passing it down to his/her offspring while most cases are sporadic.


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Apert Syndrome in Lagos

Studies had suggested Apert syn drome occured more in children with older fathers (12-14)because age was said to be responsible for new dominant autosomal mutations which themselves caused different malformations as Apert, Marfan's Syndrome and others. In the case studied, however the father was of a younger age- 29 years. Cranial malformations were the most apparent effect of acrocephalosyndactyly with prominent eyeballs due to shallow orbit and broadly spaced eyes as seen in the patient. Brachycephaly is said to be the commonest pattern of growth of head in literature but her head was round with a round face. The syndactyly of the fingers was marked and of a type 1 in which there was fusion of digits 2, 3 and 4 with 1 and 5 separate. The palm was flat and there was dimpling of the knuckles which locate the metacarpophalangeal joints which is a common finding in this type. Type 1 occured more frequently (45%) in a study done in Canada in 1995.(15) The syndactyly of the feet was a type 3 in which all the 5 toes were fused. This is also a common feature in a study done on hands and feet of patients with Apert Syndrome. (15) Radiological examination of the hands and feet of our patient showed fusion of the proximal and middle phalanges of the second, third and forth digits of both hands and extra digit of the metatarsal bone articulating with a single large ovoid bone distally in the region of the big toe bilaterally. Cardiovascular abnormalities are the most common visceral anomalies seen in patients with Apert Syndrome.(16)But the echocar-diogram result of our patient showed a normal heart both structurally and functionally. Other anormalities could be found in the genitourinary system, respiratory system and gastrointestinal system though less common. The management of a patient with Apert Syndrome requires long term follow up because most of the damages to the syst-ems are not apparent until later in life like hyperhidrosis, acneiform lesions, mental retardation, refractive error, anisometropia, stra bismus, amblyopia, exposure keratopathy and dental crowding. 24

A multidisciplinary approach is esse ntial to determine the best corrective plan for the anomalies of the patient. Genetic counselling may be helpful in those with family history of Apert and those planning to raise a family. For those already pregnant, prenatal ultrasonography especially in the third trimester would aid early diagnosis. Psychological counselling is essential for the parents of patients with Apert syndrome in view of the emotional and social adjustment due to the disability and the financial impact of multiple surgeries, stress of surgery both to patient and parents. References 1. Breugem CC, Fitzpatrick DF, Verchere C. Monozygotic twins with Apert syndrome, Cleft Palate. Craniofac J.2008 45: 101-4. 2. Satyanand T, Sachin K, Mohit S. Etiology, Symptoms and Treatment of Apert Syndrome, A Congenital Disorder; An Overview .International J of Pharma and Bio Sciences.2010 1:1-7. 3. Premalatha Kannan VP; Madhu. Apert Syndrome. J. Indian Soc. Pedod. Prev. Dent. 2010 ; 28:322-5. 4. Athanasiadis AP, Zafrakas M, Polychronou P, Florentin-Arar L, Papasozomenou P, Norbury G et al. Apert Syndrome: the current role of prenatal ultrasound and genetic analysis in diagnosis and counselling. Fetal Diagn. Ther. 2008; 24: 495-8. 5. Narang RS, Sandhu SV, Padda S, Sandhu J, Manchanda AS. An Insight into the Spectrum of Apert Syndrome-ACase Study. The Internet J Of Pediatrics and Neonatology 2011;13:1-11. 6. Ileri Z, Goyenc YB. Apert Syndrome: A case report .Euro. J. Dent. 2012l; 6:110113. 7. Kaufmann K, Baldinger S, Pratt L. Ultrasound detection of Apert Syndrome: A case Report and literature review. Am. J. Perinatol. 1997; 14 : 427-30. 8. Cohen MM Jr., Kreiborg S, Lammer EJ, Cordero JF, Mastroiacovo P, Erickson JD et al. Prevalence Study of the Apert Syndrome. Am J of Medical Genetics 1992; 42:655-659.


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9. Tolarova MM, Harris JA, Ordway DE, Vargervik K. Birth prevalence, Mutation rate, Sex ratio, Parents age, and Ethnicity in Apert Syndrome. Am J of Medical Genetics 1997; 72:394-398. 10. Quintero-Rivera F,Robson CD, Reiss RE ,Levine D, Benson C, Mulliken JB. Apert Syndrome: what prenatal radiographic findings should prompt its consideration? Prenat. Diagn. 2006 26:966-972. 11. Ofodile FA, Adeloye A. Acrocephalosyndactyly with Hydrocephalus and Dextrocardia in a Nigerian Child. J of the National Medical Association 1982;74 800-803.

12. Apert Syndrome: Accessed from http://en.wikipedia.org/wiki/Apert Syndrome 13. Erickson JD, Cohen MM. A study of Parental Age Effects on the Occurrence of Mutations for the Apert syndrome.Annals of Human Genetics 1974; 38:89-96. 14. Auroux M. Age of the Father and ` Development (Article in French). Contracept Fertil Sex. 1993 ; 21: 382-5. 15. Cohen . Jr., Kreiborg S. Hands and Feet in the Apert Syndrome. Am J of Genetics 1995; 57:82-96. 16. Cohen MM Jr., Kreiborg S. Visceral anomalies in the Apert Syndrome. Am J of Medical Genetics 1993;45: 758-760.


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