EEC Syndrome

EEC Syndrome


The exact prevalence is not known. More than 300 cases have been described in the literature.

Clinical description

The three cardinal signs of the syndrome are ectrodactyly and syndactyly of the hands and feet, cleft lip with or without cleft palate (that can result in speech defects), and abnormalities in several ectodermal structures including skin (i.e. hypopigmentated and dry skin, hyperkeratosis, skin atrophy), hair (i.e. fine and sparse hair and eyebrows), teeth (small, absent or dysplastic teeth), nails (nail dystrophy) and exocrine glands (reduction/absence of sweat, sebaceous and salivary glands). The syndrome presents a wide intra- and interfamilial clinical variability: the presence of the cardinal signs together is not mandatory and each one of them can be expressed in varying degrees of severity. Other associated clinical features include abnormalities of the genitourinary system (i.e. renal agenesis, urethral atresia, hydronephrosis), conductive or sensorineural hearing loss, choanal atresia, mammary gland/nipple hypoplasia, ophthalmological findings (i.e. lacrimal duct defects, photophobia, corneal ulcerations, keratitis, blepharitis, entropion), gland abnormalities (i.e. hypoplastic thymus, hypopituitarism, growth hormone deficiency), and on exceptional occasions, presence of a white sponge nevus, delayed developmental milestones, and malignant lymphoma. Patients do not have intellectual deficit.


In more than 90% of cases, EEC is due to missense mutations in the sequence of the TP63 gene (3q27) encoding the TP63 transcription factor that is essential for ectoderm and limb development. These cases correspond to the classical EEC syndrome (EEC type 3) and seem to present some degree of genotype-phenotype correlation. The other cases correspond to EEC syndrome type 1, which shows associated clinical features such as malformedauricles and middle and inner ear malformations, and was mapped to 7q21. EEC type 2 does not exist anymore. EEC syndrome is an autosomal dominant disorder with incomplete penetrance (between 93 and 98%) and variable expression.

Diagnostic methods

The diagnosis is based on clinical examination, X-rays of the limbs and jaw, and, according to the associated features, kidney ultrasound, ophthalmologic examinations, and skin biopsy. Genetic testing may confirm the diagnosis.

Antenatal diagnosis

Antenatal diagnosis is based on ultrasonography during the second trimester of pregnancy which may reveal the structural abnormalities. Molecular analysis by chorionic villi sampling or by amniocentesis helps in confirming the diagnosis for families for which the disease-causing mutation was identified.

Genetic counseling

Genetic counseling should be offered to affected families informing them of the 50% risk an affected person has of transmitting the disease-causing mutation. Due to germline mosaicism, unaffected parents of a child with EEC syndrome have a 4% risk of having another affected child.

Management and treatment

Management is multidisciplinary and requires evaluation by orthopedic, plastic and dental surgeons, ophthalmologists, dermatologists, and speech therapists. Surgery allows correction of orofacial and dental abnormalities and improves the function and appearance of the limbs. Ophthalmologic care (e.g. artificial tears in case of dry eyes) is necessary to avoid complications such as cataract and corneal scarring. Hot temperatures, heavy clothing, and exercise must be avoided in case of hypohidrosis.


Prognosis is good with a near to normal life expectancy. Hypohidrosis (reduction/absence of sweat glands) presents the most life-threatening complications, as it can cause seizures, coma and eventually death when not managed correctly.


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