Oral clefting, cartilaginous auricular malformations and other anomalies: A provisionally unique autosomal dominant syndrome

Abstract

We describe a provisionally unique autosomal dominant syndrome characterized by cleft lip and palate (CL/P) and unusual cartilaginous ear malformations. This is a four-generation family without male to male transmission. The proband is a five year old boy who has bilateral complete CL/P and auricular abnormalities consisting of protruding cartilaginous abnormalities located within the concha of the ear and an abnormal crus of the helix which bridges across to the anti helix. Other distinctive features include bilateral sixth nerve palsy, synophrys, broad nasal tip and mild developmental delay. There are no lip pits or branchial defects. The proband's younger brother has a bilateral CL/P and auricular abnormalities with cartilaginous protrusions in the concha, a prominent crus and pits within the concha. The mother of these children does not have a cleft, but has minor facial dysmorphism. We have examined three other affected family members, including the maternal half-aunt, who has only anosmia. Her two sons have CL/P and auricular abnormalities. One son also has bilateral sixth nerve palsy and mildly short distal phalanges of the fingers. The affected individuals have similar minor dysmorphic features. The grandfather has bilateral CL/P, ear abnormalities and anosmia. Another maternal aunt has a unilateral CL/P and anosmia. Additional studies are under way to rule out abnormalities in other organ systems. Linkage is currently being evaluated for a series of candidate genes thought to be involved in craniofacial development.

In summary, we present a probable new autosomal dominant oral clefting syndrome that has distinctive cartilaginous ear abnormalities. This condition exhibits marked variability in expression and reduced penetrance. There is variable cranial nerve involvement, mild cognitive delay, as well as some minor skeletal abnormalities in some family members. This condition appears to be distinct from other autosomal dominant oral clefting syndromes.