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Ankyloblepharon - ectodermal defects - cleft lip/palate

ORPHA1071
Synonym(s) AEC syndrome
Hay-Wells syndrome
Prevalence Unknown
Inheritance Autosomal dominant
Age of onset Neonatal
ICD-10
  • Q82.4
OMIM
UMLS
  • C1785148
MeSH
  • C535289
MedDRA -

Summary

Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is an ectodermal dysplasia syndrome (see this term) with defining features of ankyloblepharon filiforme adnatum (AFA), ectodermal abnormalities and a cleft lip and/or palate.

The prevalence of AEC is unknown.

A history of skin erosions, especially of the scalp neonatally is typical. Congenital erythroderma occurs in 78%. Skin erosions often persist intermittently for many years, evolving into alopecia and cutaneous scarring of the skin. Wound healing appears to be delayed. Other prevalent skin manifestations include hyperpigmentation and/or hypopigmentation, often reticulated, and palmar and plantar changes with effaced dermatoglyphics. Nail changes are universal and variable and include hyperconvexity, pseudoptyergium and frayed distal margin with nail plate resorption. Hypotrichosis is common and hair is thin, brittle, wiry and uncombable. Mild hypohidrosis is always present. Nearly all cases have clefting abnormalities, ranging from submusous cleft palate, to soft and/or hard cleft palate, cleft lip or a combination. Other oroauditory findings include recurrent otitis media, canal stenosis and over 90% have a conductive hearing loss associated with a delay of speech development. AFA affects most neonates (70%) but is not always evident and eyes often are deficient of lacrimal puncta. In childhood, other facial features become more apparent and include broad nasal root, hypoplastic alae nasi, short philtrum, thin vermillion border, maxillary hypoplasia and small mandible. Over time, cone-shaped teeth and hypodontia become evident. Other anomalies are limb changes with syndactyly of fingers and toes most common, hypospadias (males 78%) and trismus (less frequently described). Failure to thrive, growth delay and gastrointestinal issues are also common.

AEC is caused by typically missense mutations in the Tumor suppressor gene TP63. Over 4/5th of the reported mutations occur in the steril alpha motif domain, and about 1/5th occur in the transactivation inhibitory domain of TP63.

Clinical features can be diagnostic. Light or scanning microscopy of the hair in combination with genetic testing may ascertain diagnosis.

Differential diagnosis may include epidermolysis bullosa simplex, disorders of cornification, CHAND syndrome and hypohidrotic ectodermal dysplasia (see these terms). Allelic disorders include ADULT syndrome, EEC syndrome, limb-mammary syndrome and split hand/foot malformation type 4 (see these terms). Rapp-Hodgkin syndrome is not a separate disease entity, but is now considered part of the disease spectrum of AEC.

In case of family history, prenatal diagnosis is possible by genetic testing of amniocentesis or chorionic villus sampling.

AEC follows an autosomal domainant transmission. About 70% of cases are caused by a de novo mutation in TP63. In case of family history, genetic counseling is recommended.

AFA and cleft palate may require surgical intervention, as well as dental abnormalities requiring prosthetics. Efforts to prevent secondary infections in skin erosions comprise gentle wound care and dilute bleach soaks. Secondary infections should be cultured and treated appropriately. Extra care should be taken to avoid complications in infants with severe skin erosions. Extensive grafting procedures are not recommended. Hearing loss, growth and gastrointestinal problems should be monitored regularly. Gastrostomy is common. Psychological consequences of ectodermal defects should be addressed.

Overall prognosis is good with most having normal life expectancy. Unfortunately infants with extensive skin erosions are at risk of premature death due to complications including sepsis and fluid/electrolyte abnormalities. Quality of life and psychosocial functioning is often mildly but variably impacted.

Expert reviewer(s)

  • Dr Alanna BREE

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Detailed information

Clinical genetics review
  • EN (2010)
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