Tetramelic Deficiencies, Ectodermal Dysplasia, Deformed Ears, And Other Abnormalities

Clinical Features

Freire-Maia (1970) described a Brazilian family in which a brother and sister and 2 deceased brothers showed severe absence deformities of all limbs, hypotrichosis, abnormal teeth, hypoplastic nipples and areolae, and deformed auricles. The consistent features included hypoplastic nails, hypogonadism, thyroid enlargement, incomplete cleft lip, mental retardation, and ECG and EEG abnormalities. Both living sibs showed an excess of tyrosine and/or tryptophane in the urine. Parental consanguinity was denied, but the parents came from the same farm in one of the most inbred areas of Brazil.

Pavone et al. (1989) described a 19-year-old woman, born to first-cousin parents, who had severe upper limb anomalies, structural abnormalities of the ear, nasolacrimal duct obstruction, dysplastic fingernails, and sparse eyebrows and eyelashes.

Zankl et al. (2004) raised the possibility that odontotrichomelic syndrome might be present in the patient they reported with ectodermal dysplasia affecting hair, teeth, and nails and malformations of all 4 extremities, including absence of several rays in the hands and feet. This was a sporadic case and parental consanguinity was considered unlikely. The patient was evaluated at ages 2 years 9 months and 22 years. At that time scalp hair was sparse and thin. Eyebrows and eyelashes were present but sparse. His dentition contained only 10 teeth, which were hypoplastic and peg-shaped. He played different sports and reported sweating heavily. Stents had been implemented for nasolacrimal duct obstruction.

Inheritance

Zankl et al. (2004) stated that autosomal recessive inheritance was likely in the patients reported by both Freire-Maia (1970) and Pavone et al. (1989).

Molecular Genetics

Exclusion Studies

Zankl et al. (2004) found no mutation in the p63 gene (603273) in the patient they reported. They thought that a mutation in the PVRL1 gene (600644), which is mutant in the Margarita Island type of ectodermal dysplasia/Zlotogora-Ogur syndrome (see 225060), a recessive disorder, was a possibility.