The symptoms of AEC syndrome are highly variable, even among members of the same family. In addition, the small number of identified cases, the lack of large clinical studies, and the possibility of other genes or factors influencing the disorder prevent physicians from developing a completely accurate picture of associated symptoms and prognosis. Affected individuals or their parents should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.
Many of the symptoms associated with AEC syndrome are present at birth (congenital). Many infants will have abnormal strands of tissue that connect the upper eyelids with the lower eyelids causing them to be fused together, a condition known as ankyloblepharon filiforme adnatum. Ankyloblepharon affects approximately 70% of individuals with AEC syndrome and is generally not seen in other TP63-related disorders.
Most infants will have some degree of skin erosion, ranging from mild involvement of a specific area to severe, even life-threatening, involvement of the whole body. The scalp is commonly involved and is usually affected more severely than other areas. Severe scalp erosions can cause a generalized loss of hair (hypotrichosis) as well as patchy areas where hair loss is followed by the formation of scar tissue (scarring alopecia). Skin erosions may recur periodically throughout childhood and sometimes adulthood. The head and neck, palms and soles, and skin folds are most often affected. Skin erosions can be slow to heal and a considerable source of discomfort, Pain and disability. In severe cases, these persistent skin erosions can lead to frequent infection and potentially life-threatening complications such as sepsis.
Additional Skin abnormalities may also be present. The characteristic skin erosions may be associated with a widespread (diffuse) reddish discoloration (erythroderma). The affected skin can also appear shiny and waxy (collodion membrane). Affected individuals may also develop areas of darkened or faded skin color (hyper- or hypo-pigmentation). Dry, scaly patches of skin may form on the palms and soles (palmar-plantar hyperkeratosis) as well as tiny, hardened Bumps (punctate keratoderma). Increased numbers and depth of skin lines on the palms may also occur (hyperlinearity). Hyperkeratosis may also affect the knees and elbows.
All affected individuals have oral clefting abnormalities. Some have only a cleft or groove on the roof of the mouth (palate), some have only a cleft lip, and others have both. A Cleft palate or lip is usually obvious at birth. However, a Cleft palate can vary in size and location and some small clefts can go unnoticed or undetected until later in life. Cleft palate occurs more frequently than cleft lip.
AEC syndrome also causes decreased sweat production (hypohidrosis), which causes some affected individuals to be uncomfortable or feel “overheated” when the temperature rises (heat intolerance). Hypohidrosis is due, in part, to reduced number or absence of sweat glands.
Additional common findings in AEC syndrome include sparse, wiry, brittle hair that is usually light colored. In some cases, flattened, twisted hair shafts (pili torti) may be present. Eyebrows and eyelashes are also sparse. Nail changes may also occur and can vary greatly among individuals. Such changes include misshapen or malformed fingernails and toenails, abnormally small nail plates (micronychia), frayed edges of the nails, and absent nails. Hair and nail abnormalities become more apparent as affected individuals grow older.
Dental abnormalities are also common and can include one or more missing teeth (hypodontia), widely spaced teeth, and malformed or underdeveloped (hypoplastic) teeth. The lower jaw may also be small and underdeveloped (maxillary hypoplasia).
Affected individuals may also have narrowing (atresia) or absence of the opening in the edge of each eyelid that is linked to the tear duct (lacrimal punctata). This can lead to obstruction of the tear ducts and predispose to recurrent eye crusting and conjunctivitis. Many individuals with AEC report chronic dry eyes. Chronic Inflammation of the eyelids (blepharitis) has also been reported.
Less often, certain limb anomalies have been associated with AEC syndrome including webbing of certain fingers or toes (syndactyly) and fingers that are stuck in a bent or flexed position (camptodactyly).
Some children experience chronic middle ear infections (otitis media) and approximately 90% develop Hearing loss due to the failure of sound waves to be sent (conducted) through the middle ear (conductive hearing loss). Hearing loss can cause delays in speech development.
Poor weight gain, growth deficiencies and Short stature can also occur. Additional findings that have been reported in individuals with AEC syndrome include abnormally small ears, a broad bridge of the nose, an abnormally short groove that runs from the top of the upper lip to the nose (philtrum), an abnormally small mouth (microstomia), and the inability to completely open the mouth (trismus). In affected males, the opening of the small tube that carries urine from the bladder to outside of the body (urethra) may be abnormally located on the underside of the penis (hypospadias).