Apert syndrome
Shyam Verma MD1 and Michelle Draznin MD2
Dermatology Online Journal 11 (1): 15

1. Pratapgunj Baroda 390 002, India. vermaderma@rediffmail.com
2. Department of Dermatology, University of California, Davis



Introduction

Over the past several decades tremendous advances have been made in the prevention and treatment of developmental anomalies. This metamorphosis in our conceptualization of developmental malformations has led to an improved ability to handle and prevent them. Despite such improvements, developmental malformations remain a significant cause of morbidity worldwide. Even when the mode of inheritance is well established, some conditions continue to exhibit a large number of sporadic occurrences, which makes their eradication virtually impossible. As such, it is incumbent on us to learn us much as possible about these conditions. In this way, we can become better clinicians and impart better care to those who so desperately need it.

Apert syndrome was first described by Eugene Apert in 1906. He described a triad of craniosynostosis, syndactyly and maxillary hypoplasia. It is known to be inherited in an autosomal dominant fashion, but most cases are sporadic. The sporadic cases are postulated to be associated with advanced paternal age. The incidence of Apert syndrome is approximately one in 50,000 births. Some investigators state that 4.5 percent of all craniosynostosis represent Apert syndrome [1].


Clinical synopsis


Figure 1 Figure 2
Fusion of digits (syndactyly) and discolored nails of feet (Fig. 1).
Syndactyly and fusion of nails (synonychia) of digits of hands (Fig. 2).

Figure 3 Figure 4
Prominent mandible, ocular hypertelorism (Fig. 3).
Cleft palate (Fig. 4).

A 10-year-old boy presented with the chief complaint of excessive sweating of his feet. This child was also noted to have symmetric syndactyly of all digits of the hands and feet (Figs. 1 and 2). His toenails were discolored and fragile and a KOH examination was positive for yeast. His fingernails from the three middle digits were fused together (so-called "synonychia"). This patient also exhibited midface hypoplasia, exophthalmia, ocular hypertelorism, and a cleft palate (Figs. 3 and 4). These characteristics helped land the diagnosis of Apert syndrome.


Discussion

The infant Apert skull is characterized by premature fusion of the coronal sutures and by a wide calvarial midline defect that starts at the glabella and ends at the posterior fontanelle. Many of those affected also have agenesis of the corpus collosum, progressive hydrocephalus, and hippocampal abnormalities [2]. Early surgical intervention to correct the craniosynostosis is crucial in order to realize the highest chances for normal development. The ocular orbits are shallow and the accompanying exophthalmia may lead to blindness. The ocular manifestations, hypertelorism and exophthalmia, seem to be present in all case reports.

The oral cavity of Apert patients is also characteristic. The findings include a reduction in the size of the maxilla, particularly in the anterioposterior direction. This reduction may result in tooth crowding. Cleft palate or bifid uvula is found in approximately 75 percent of those affected. Dental anomalies such as impacted teeth, delayed eruption, ectopic eruption, supernumerary teeth, and thick gingiva are also common [1].

Important skin manifestations of Apert syndrome include hyperhidrosis (our patient's presenting complaint), brittle nails, and synonychia. This combination often leads to candidal infection and colonization. Severe acne that responds only to isotretinoin is also seen in association with Apert syndrome [3]. Other reported findings include hypopigmentation, hyperkeratosis, and excessive skin wrinkling of the forehead, shoulders, elbows, and knuckles [4].

Table 1: Skin manifestations of Apert syndrome
Hyperhidrosis
Synonychia
Brittle nails
Severe acne in puberty
Interruption of the eyebrows
Hypopigmentation
Hyperkeratosis
Paronychial infections of plantar skin
Excessive skin wrinkling of forehead
Dimples at knuckles, shoulders and elbows

Recent years have brought about an upsurge in the study of fibroblast-growth-factor receptors, FGFRs, as they pertain to human development. At least fifteen different genetic dysplasias such as Apert syndrome have been linked to FGFRs [5]. The mutation is known to be a Ser252 Trp mutation in the FGFR2 gene [6]. The epidemiology of Apert syndrome is such that the incidence of sporadic births increases exponentially with increasing paternal age, and some investigators have found that this mutation is more common in the sperm of older men [7]. Experiments have indicated that FGFR2 may act as a negative regulator of bone growth.

Until there is a means to correct the molecular defect, we must rely on a strong multidisciplinary approach to patients with Apert syndrome. Neurosurgeons, plastic surgeons, otorhinolaryngologists, orthodontists, ophthalmologists, radiologists, geneticists, pediatricians, and dermatologists must all work in concert to care for patients with Apert syndrome. Early surgical intervention is imperative for optimal outcomes. Subsequent treatment should be tailored to each individual patient's needs.

References

1. Albuquerque MA, Cavalcanti MG. Computed tomography assessment of Apert syndrome. Pesqui Odontol Bras. 2004 Jan-Mar;18(1):35-9. Epub 2004 Jul 20. PubMed

2. Vijayalakshmi AM, Menon A. Apert syndrome. Indian Pediatr. 2002 Sep;39(9):876-8. PubMed

3. Downs AM, Condon CA, Tan R. Isotretinoin therapy for antibiotic-refractory acne in Apert's syndrome. Clin Exp Dermatol. 1999 Nov;24(6):461-3. PubMed

4.Cohen MM Jr, Kreiborg S. Cutaneous manifestations of Apert syndrome. Am J Med Genet. 1995 Jul 31;58(1):94-6. PubMed

5. McIntosh I, Bellus GA, Jab EW. The pleiotropic effects of fibroblast growth factor receptors in mammalian development. Cell Struct Funct. 2000 Apr;25(2):85-96. PubMed

6. Doutetien C, Laleye A, Tchabi S, Biaou O, Lawani R, Deguenon J, Darboux R, Gnamey D, Bassabi SK. [Apert's syndrome: a case report] J Fr Ophtalmol. 2003 Sep;26(7):738-42. PubMed

7. Glaser RL, Broman KW, Schulman RL, Eskenazi B, Wyrobek AJ, Jabs EW. The paternal-age effect in Apert syndrome is due, in part, to the increased frequency of mutations in sperm. Am J Hum Genet. 2003 Oct;73(4):939-47. Epub 2003 Jul 31. PubMed

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Title:

Apert syndrome

Journal Issue:

Dermatology Online Journal, 11(1)

Author:

Verma, Shyam;
Draznin, Michelle

Publication Date:

2005

Publication Info:

Dermatology Online Journal, UC Davis

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