Ectrodactyly, Ectodermal Dysplasia, and Clefting (EEC) Syndrome

At a glance

Autosomal dominant inherited syndrome characterized by the triad of ectrodactyly, ectodermal dysplasia, and facial clefts (lip and palate). Other clinical features include maxillary hypoplasia, mild malar hypoplasia, choanal atresia, conductive hearing loss, photophobia and blepharophimosis, dacryocystitis, cryptorchidism, hypogonadotropic hypogonadism renal agenesis or dysplasia, hydronephrosis, occasionally mental retardation, central diabetes insipidus.

Synonyms

EEC Syndrome; Rosselli-Gulienetti Syndrome; Zlotogora-Ogur Syndrome; Bowen-Armstrong Syndrome; Cleft Lip/Cleft Palate-Lobster-Claw Deformity Syndrome; Ectrodactyly-Cleft Lip/Palate Syndrome; Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate Syndrome; Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate Syndrome; Split Hand-Cleft Lip/Palate and Ectodermal (SCE) Dysplasia; Walker-Clodius Syndrome; Split Hand-Split Foot-Ectodermal Dysplasia-Cleft Syndrome.

History

The first report of a patient affected with ectodermal dysplasia was published in 1848 by J. Thurman. However, the term “ectodermal dysplasia” was coined by Weech in 1929. In 1961, D. Rosselli and R. Gulienetti reported four patients with hypohidrosis, hypotrichosis, microdontia, dystrophic nails, cleft lip and palate, deformities of the extremities, and malformations of the genitourinary system. Syndactyly was the prominent digital deformity. Rudiger and Freire-Maia reported in 1970 reported a very similar medical presentation that they named the EEC Syndrome for Ectrodactyly-Ectodermal Dysplasia-Cleft Lip/Palate Syndrome.

Incidence

The individual frequency of ectrodactyly is reported to be 1.5 per 100,000 live births and 1 per 100,000 live births for cleft palate with or without cleft lip. The occurrence of all three disorders in one, ie, ectrodactyly, ED, and cleft lip/palate is reported to be approximately 1.5 per 100 million. More than 250 cases have been published in the medical literature.

Genetic inheritance

Autosomal dominant inheritance with variable phenotypic expression. The gene locus has been mapped to 7p11.2-q21.3 (EEC1). There are at least four other syndromes caused by mutations of the TP63 gene including AEC/Hay-Wells Syndrome, Rapp-Hodgkin Syndrome, Limb-Mammary Syndrome, and ADULT Syndrome. In addition, TP63 mutations have also been reported as the cause of nonsyndromic split hand/foot malformation and nonsyndromic cleft lip/palate. Chromosome 19 is linked to a variety that is referred to as EEC2. EEC3 has been mapped to 3q27, which is also the location for the limb-mammary and the ☞ADULT Syndrome. A number of sporadic cases have been described.

Diagnosis

Cardinal features are ectrodactyly of hands and feet, ectodermal dysplasia with severe keratitis, and cleft lip/palate. There are variable manifestations, and no sign is obligatory for the diagnosis.

Clinical aspects

Facial features included cleft lip with or without cleft palate (72% of patients), maxillary hypoplasia, mild malar hypoplasia, partial anodontia, microdontia, and choanal atresia. Mental retardation (7%), growth hormone deficiency, hypopituitarism, and central diabetes insipidus (rare) are additional features. Genitourinary malformations (50% of patients) include renal dysplasia and agenesis. Conductive hearing loss is present in approximately 14% of patients. Lacrimal duct anomalies result in repeated infections of the eyes. ...