Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome

Other Names: Ankyloblepharon ectodermal defects cleft lip/palate; AEC syndrome; Hay-Wells syndrome

Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome (AEC syndrome) is a form of ectodermal dysplasia, a group of conditions characterized by abnormal development of ectodermal tissues including the skin, hair, nails, teeth, and sweat glands.

A condition known as Rapp-Hodgkin syndrome has signs and symptoms that overlap considerably with those of AEC syndrome. These two syndromes were classified as separate disorders until it was discovered that they both result from mutations in the same part of the same gene. Most researchers now consider Rapp-Hodgkin syndrome and AEC syndrome to be part of the same disease spectrum.

Epidemiology

AEC syndrome is a rare condition; its prevalence is unknown. All forms of ectodermal dysplasia together occur in about 1 in 100,000 newborns in the United States.

Cause

AEC syndrome is caused by mutations in the TP63 gene. This gene provides instructions for making a protein known as p63, which plays an essential role in early development. The p63 protein is a transcription factor, which means that it attaches (binds) to DNA and controls the activity of particular genes. The p63 protein turns many different genes on and off during development. It appears to be especially critical for the development of ectodermal structures, such as the skin, hair, teeth, and nails. Studies suggest that it also plays important roles in the development of the limbs, facial features, urinary system, and other organs and tissues.

The TP63 gene mutations responsible for AEC syndrome interfere with the ability of p63 to turn target genes on and off at the right times. It is unclear how these changes lead to abnormal ectodermal development and the specific features of AEC syndrome.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Signs and symptoms

Among the most common features of AEC syndrome are missing patches of skin (erosions). In affected infants, skin erosions most commonly occur on the scalp. They tend to recur throughout childhood and into adulthood, frequently affecting the scalp, neck, hands, and feet. The skin erosions range from mild to severe and can lead to infection, scarring, and hair loss. Other ectodermal abnormalities in AEC syndrome include changes in skin coloring; brittle, sparse, or missing hair; misshapen or absent fingernails and toenails; and malformed or missing teeth. Affected individuals also report increased sensitivity to heat and a reduced ability to sweat.

Many infants with AEC syndrome are born with an eyelid condition known as ankyloblepharon filiforme adnatum, in which strands of tissue partially or completely fuse the upper and lower eyelids. Most people with AEC syndrome are also born with an opening in the roof of the mouth (a cleft palate), a split in the lip (a cleft lip), or both. Cleft lip or cleft palate can make it difficult for affected infants to suck, so these infants often have trouble feeding and do not grow and gain weight at the expected rate (failure to thrive).

Additional features of AEC syndrome can include limb abnormalities, most commonly fused fingers and toes (syndactyly). Less often, affected individuals have permanently bent fingers and toes (camptodactyly) or a deep split in the hands or feet with missing fingers or toes and fusion of the remaining digits (ectrodactyly). Hearing loss is common, occurring in more than 90 percent of children with AEC syndrome. Some affected individuals have distinctive facial features, such as small jaws that cannot open fully and a narrow space between the upper lip and nose (philtrum). Other signs and symptoms can include the opening of the urethra on the underside of the penis (hypospadias) in affected males, digestive problems, absent tear duct openings in the eyes, and chronic sinus or ear infections.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Ankyloblepharon(Adhesion of eyelids)
• Coarse hair(Coarse hair texture)
• Conductive hearing impairment(Conductive deafness)
• Dystrophic fingernails(Poor fingernail formation)
• Dystrophic toenail(Poor toenail formation)
• Hyperconvex fingernails
• Hypohidrosis(Decreased ability to sweat)
• Non-midline cleft lip
• Wide nasal bridge(Broad nasal bridge)

30%-79% of people have these symptoms

• Abnormality of dental enamel(Abnormal tooth enamel)
• Conical tooth(Cone shaped tooth)
• Generalized hyperpigmentation
• Hypodontia(Failure of development of between one and six teeth)
• Micrognathia(Little lower jaw)
• Palmoplantar keratoderma(Thickening of palms and soles)
• Sparse and thin eyebrow(Thin, sparse eyebrows)
• Sparse eyelashes(Scant eyelashes)
• Submucous cleft hard palate
• Submucous cleft soft palate
• Widely spaced teeth(Wide-spaced teeth)

5%-29% of people have these symptoms

• Abnormality of the voice(Voice abnormality)
• Absent lacrimal punctum
• Clinodactyly of the 5th finger(Permanent curving of the pinkie finger)
• Delayed eruption of teeth(Delayed eruption)
• Finger syndactyly
• Protruding ear(Prominent ear)
• Supernumerary nipple(Accessory nipple)
• Ventricular septal defect(Hole in heart wall separating two lower heart chambers)

Diagnosis

Ankyloblepharon filiforme adnatum typically manifest as strands of tissue that completely or partially fuse the upper and lower eyelids. In the latter instance, they may be barely perceptible and lyse spontaneously. Although a definitive part of the syndrome, ankyloblepharon may not be present or detected in up to 50% of cases. Ectodermal defects typically manifest as sparse wiry hair, skin erosions and unique pigmentary skin changes, nail changes, dental changes, and subjective decrease in sweating capacity. Note: (1) Starch iodide sweat testing of the palms is rarely helpful in documenting sweating ability. (2) Scalp erosions are characteristic of AEC syndrome and are NOT seen in other TP63-related disorders. Cleft lip/palate presents in nearly 100%; the spectrum includes submucous cleft palate only, cleft of the soft and/or the hard palate only, cleft lip only, and the combination of cleft lip and cleft palate. In a series of 18 affected individuals: 44% had cleft lip (~1/3 bilateral); 100% had some form of palatal cleft (cleft hard palate: 56%; cleft soft palate: 89%; submucous cleft palate: 17%). Craniofacial findings include the following:

• Maxillary hypoplasia (reported in 94%)
• Small mandible (reported in 65%)
• Broad nasal bridge (76%)
• Hypoplastic alae nasi (94%)
• Thin vermilion border of the upper lip (82%)
• Microstomia (94%)
• Trismus (44%)

Treatment

A multidisciplinary approach is recommended including regular evaluations with specialists in clinical genetics, dermatology, ophthalmology, otolaryngology, audiology, dentistry and prosthodontics, plastic surgery, gastroenterology, and psychiatry.

Ankyloblepharon filiforme adnatum. These strands of tissue between the upper and lower eyelids are often small and autolyse shortly after birth; larger ones may require surgical separation by an ophthalmologist.

Ectodermal defects

• Wigs can be used, if desired, for the sparse hair and alopecia.
• There are no known therapies for the nail or skin pigment changes.
• Dentures should be considered in early childhood and the possibility of dental implants should be considered in the teens or early adult years.
• Sweating is not severely impaired and does not require special care.

Skin erosions. The skin erosions are difficult to treat and prone to excessive ineffective granulation response; they are at increased risk for secondary infection and are not responsive to most standard wound care regimens or antibiotic therapy . Skin erosions should be treated with gentle wound care and periodic, dilute bleach soaks (Dakins solution) to prevent secondary infection.

Occlusive dressings should not be used as they tend to stimulate granulation tissue.

Secondary infections should be treated with topical or oral antibiotics or antifungal agents when appropriate. Empiric treatment (i.e., use of antibiotic without culture-proven infection) is not recommended.

Cleft lip/palate. Clefting should be addressed as soon as developmentally possible. Typical feeding issues associated with clefting are seen and include: poor suck, difficulty coordinating feeding and breathing, and excessive air intake. A nurse, nutritionist, pediatrician, speech therapist, or other specialist familiar with the management of feeding issues in children with cleft lip/palate should be consulted. Early referral to a craniofacial surgeon for planning for surgical cleft repair is indicated.

Other

• Weight should be followed closely with assessment for signs of failure to thrive. If optimization of oral caloric intake fails to improve growth, gastrostomy tube placement may be considered.
• Myringotomy is indicated as needed for conductive hearing loss resulting from chronic otitis media.
• Significant breast asymmetry in women may be corrected through plastic surgery.
• Psychological impact of the phenotypic features of the disorder on patient and family should also be considered and referrals made to psychiatry or psychology as appropriate.

NIH genetic and rare disease info

• NIH info on Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome

Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome is a rare disease.

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