camptodactyly

Ablepharon-Macrostomia Syndrome

Clinical Characteristics

Ocular Features

The clinical features of this syndrome remain to be fully delineated.  Important ocular anomalies include malformations and sometimes absence of the upper and lower eyelids.  The eyelashes and eyebrows may be sparse or even missing.  The lid fissures, if present, may be shortened.  Deformities of the eyelids can lead to corneal exposure and secondary vision loss. 

Systemic Features

Other facial malformations include macrostomia which may be secondary to aberrant lip fusion.  Micrognathia has been described.  The external ears are often rudimentary, sometimes described as rosebuds.  The nasal bridge is low and the nostrils anteverted.  The zygomatic arches may be absent.  The nipples are often missing as well.  Scalp hair is sparse or even absent while the skin is dry, coarse, and often has redundant folds (cutis laxa).  Mild skin syndactyly, camptodactyly, finger contractures, and shortening of metacarpals have been noted.  The genitalia are often ambiguous and some patients have had ventral hernias.  Hearing loss can be a feature.  Growth retardation has been seen but developmental delays if present are mild.  Intelligence can be normal. 

Genetics

The majority of sibships suggest autosomal recessive inheritance although autosomal dominant inheritance has been proposed for several. One male child has been reported to have a partial deletion of chromosome 18 but other complex rearrangements were also present. 

Treatment Options

Cosmetic surgery can correct at least some of the malformations. Vigorous effort may be required to maintain corneal surface wetting. 

References

Rohena L, Kuehn D, Marchegiani S, Higginson JD. Evidence for autosomal dominant inheritance of ablepharon-macrostomia syndrome. Am J Med Genet A. 2011 Apr;155(4):850-4.

PubMed ID: 
21595001

Stevens CA, Sargent LA. Ablepharon-macrostomia syndrome. Am J Med Genet. 2002 Jan 1;107(1):30-7.

PubMed ID: 
11807864

Cruz AA, Souza CA, Ferraz VE, Monteiro CA, Martins FA. Familial occurrence of ablepharon macrostomia syndrome: eyelid structure and surgical considerations. Arch Ophthalmol. 2000 Mar;118(3):428-30.

PubMed ID: 
10721975

Ferraz VE, Melo DG, Hansing SE, Cruz AA, Pina-Neto JM. Ablepharon-macrostomia syndrome: first report of familial occurrence. Am J Med Genet. 2000 Oct 2;94(4):281-3.

PubMed ID: 
11038439

Focal Dermal Hypoplasia

Clinical Characteristics

Ocular Features

Features have considerable heterogeneity and few patients have all of them.  Some ocular abnormalities are found in 40% of patients.  Microphthalmia is common and many patients (30%) have colobomas of the iris and choroid.  Some patients have dislocated lenses.  Distinctive peripheral corneal lesions consisting of discrete vascularized subepithelial opacities have been described.  Occasional patients have conjunctival or lid margin papillomas.  Strabismus and nystagmus are common.

Systemic Features

This disorder has a wide variety of clinical features and many occur in only a few patients.  The skin has focal areas of hypoplasia with hypopigmentation, often appearing in a streak or linear pattern.  These areas may be present at birth and contain bullae or urticarial lesions with signs of inflammation.  Telangiectases and herniated fat may appear in these areas.   Oral, esophageal, and laryngeal fibrovascular papillomas occur but they may also be seen in the perineal, vulvar, and perianal areas.  These may be large, friable, and recurrent.  The teeth erupt late and are usually hypoplastic.  The nails are often dysplastic and the hands and feet may be ‘split’ with syndactyly of the third and fourth fingers giving a ‘lobster claw’ appearance.  Polydactyly may be present.  Most have thin ‘protruding’ ears.  A variety of skeletal anomalies have been reported including absence of metatarsals and metacarpals.  A considerable number of patients have mild to moderate mental deficits.  Severely affected females may die in infancy.

Genetics

This is considered an X-linked dominant disorder with lethality in males.  However, numerous affected males (>30) and rare instances of father-to-daughter transmission have been reported and it has been suggested that half-chromatid mutations or postzygotic somatic mosaicism in these males might be responsible.  Mutations in the PORCN gene (Xp11.23) have been associated with FDH.

Treatment Options

Surgery may be required for the papillomas if they are obstructive.

References

Brady PD, Van Esch H, Fieremans N, Froyen G, Slavotinek A, Deprest J, Devriendt K, Vermeesch JR. Expanding the phenotypic spectrum of PORCN variants in two males with syndromic microphthalmia. Eur J Hum Genet. 2014 Jul 16.  [Epub ahead of print] PubMed PMID: 25026905.

PubMed ID: 
25026905

Maas SM, Lombardi MP, van Essen AJ, Wakeling EL, Castle B, Temple IK, Kumar VK, Writzl K, Hennekam RC. Phenotype and genotype in 17 patients with Goltz-Gorlin syndrome. J Med Genet. 2009 Oct;46(10):716-20.

PubMed ID: 
19586929

Lueder GT, Steiner RD. Corneal abnormalities in a mother and daughter with focal dermal hypoplasia (Goltz-Gorlin syndrome). Am J Ophthalmol. 1995 Aug;120(2):256-8.

PubMed ID: 
7639315

Goltz RW. Focal dermal hypoplasia syndrome. An update. Arch Dermatol. 1992 Aug;128(8):1108-11.

PubMed ID: 
1497368