DISEASE CARD

Disease group: Ectodermal Dysplasia
DISEASE NAME: AEC Syndrome
Synonymous: Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate, Hay-Wells-Syndrome
Estimated prevalence: -
OMIM: 106260
Inheritance: Autosomal Dominant
Gene (s) p63 (603273)

Definition

AEC syndrome is a rare autosomal dominant disorder characterized by ankyloblepharon (fusion of the eyelids), ectodermal dysplasia and cleft lip/palate. It was first described by Hay and Wells in 1976. The disease is caused by mutations in the transcription factor p63 gene which has a gene map locus 3q27.

Clinical Description

Infants are born with ankyloblepharon (in 70%), variable ectodermal dysplasia features and cleft lip or palate (in 100%). Adhesions of the upper and lower eyelids can be partially and lyse before they are recognized as such. Scalp erosions and scalp dermatitis are common clinical findings, occurring recurrent and intermittent, especially in infancy, when children may suffer recurrent scalp infections, often leading to scarring alopecia. Skin involvement may also be more generalized, with the majority of individuals having widespread dry, atrophic, eczematous skin or congenital erythroderma and subjective decreased sweat production. Postinflammatory pigmentary changes are the causes of cutaneous depigmentation and scarring seen in children. Hair is usually sparse, especially on the scalp, but eyebrows and eyelashes are also commonly affected. Hair that does develop is abnormal, coarse, wiry and difficult to comb. Another common clinical feature is hypodontia. When teeth are present however, they are abnormal in appearance, i.e. pointed or ‘peg-shaped’. All patients develop nail changes (nail dystrophy, hyperconvex nail plates, micronychia (abnormally small nail plates), distal frayed edges or absent nails) in varying degrees. Absence of lacrimal puncta commonly becomes obvious in early childhood due to chronic conjunctivitis and blepharitis. More than 90% of children have conductive hearing loss, often with secondary speech delay.

AEC syndrome is a non-progressive condition. In the majority of cases, areas of scalp dermatitis and erosions improve with age. However, there remains great variability of other ectodermal dysplasia features into adulthood. (table 1)

Pathogenesis

Many affected individuals have been found to have mutations within the p63 gene. The mutations are most commonly missense mutations which are clustered within the SAM domain of the gene. The p63 gene is a p53 homolog, and is an important transcription factor in the development of normal skin and ectodermal structures. However, its exact function remains poorly understood. AEC syndrome is an autosomal dominant condition, which has great variability and clinical overlap with another ectodermal dysplasia syndrome: Rapp-Hodgkin Syndrome (heterozygous mutation in p63 gene; OMIM 129400).

Diagnosis

Diagnosis is usually made by assessment of the clinical features either at, or soon after birth. In those individuals who have milder phenotypic features, the diagnosis becomes evident when hair, teeth or nails fail to develop normally. If a p63 gene mutation is identified, this will help confirm the diagnosis. No other diagnostic tests are available at present.

Treatment

The management of AEC syndrome requires the expertise from various specialties. Soon after birth, an affected infant will require surgical repair of his/her ankyloblepharon and cleft lip or palate defects. Topical emollients, antiseptic agents and NA dressings are required for any eroded areas which tend to be most severe on the scalp. Antibiotic therapy is often required to treat any secondary infections. Dental treatment is extremely important for these individuals. Many require successive dentures as a child with addition of dental implants and bridges later in adult life.

 
  TP63-Related Disorder
Feature AEC ADULT EEC3 Limb-
Mammary
SHFM4 Isolated
CL/P
Inheritance AD AD AD AD AD AD
Ankyloblepharon filiforme adnatum X          
Ectodermal dysplasia: X X X    Rare  
  • Hypohidrosis (mostly subjective)**
X X   X    
  • Nail dysplasia
X X Mid X    
  • Sparse hair
X X X      
  • Tooth abnormalities
X X X X    
Cleft lip/palate X   X X    X
Split-hand/foot malformation/syndactyly X X X X X  
Lacrimal duct obstruction X X X X    
Dermal erosions X          
Hypopigmentation X X X      
Hypospadias X   X      
Trismus (“lockjaw”) X          
Excessive freckling   X        
Hypoplastic breasts   X    X    
Hypoplastic nipples   X    X    

 

AD = autosomal dominant; ADULT = acro-dermato-ungual-lacrimal-tooth; AEC =  Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome; CL/P = cleft lip/cleft palate; EEC = ectrodactyly (split-hand/foot malformation), ectodermal dysplasia, clefting; SHFM4 = split-hand/foot malformation type 4

* strands of tissue that completely or partially fuse the upper and lower eyelids

** starch iodide sweat testing of the palms is rarely helpful in documenting sweating ability

 

References

Sutton VR, van Bokhoven H. TP63-Related Disorders (last revision 12/2019). In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, et al., editors. GeneReviews(®). Seattle (WA): University of Washington, Seattle; 1993