Question Mark Ears, Isolated

A number sign (#) is used with this entry because of evidence that isolated question mark ears (QME) are caused by heterozygous mutation in the EDN1 gene (131240) on chromosome 6p24. Homozygous mutation in EDN1 causes auriculocondylar syndrome-3 (ARCND3; 615706).

Description

Question mark ear is an auricular abnormality characterized by a cleft between the lobule and the lower part of the helix, sometimes accompanied by a prominent or deficient upper part of the helix, shallow skin dimple on the posterior surface of the ear, or transposition of the ear lobe/antitragus. It is more prevalent among boys than girls (2:1), usually sporadic, and can be unilateral or bilateral (Shkalim et al., 2008).

Clinical Features

Cosman et al. (1970) described 2 unrelated patients with question mark ears. The first was a 38-year-old Puerto Rican man who had a unilateral deformity of the left ear, with prominence and protrusion of the upper third of the ear, an apparent absence of the helix and distal scapha in the middle third, and disjunction of the otherwise normal lobule from the rest of the ear in the lower third. There was no family history of ear abnormalities. The other patient was a 5-year-old black boy who had the same defect of the ears bilaterally, with a shallow 2-mm skin dimple posteriorly bilaterally and a skin tag on the left. His eardrums and hearing were normal. The boy had an apparently identical twin brother with completely normal ears.

Cosman (1984) provided follow-up on the 2 patients described by Cosman et al. (1970), both of whom underwent repair of their ears with good cosmetic results. Cosman (1984) stated that 8 or 9 cases of question mark ears had been reported, some of which were associated with other anomalies (see, e.g., auriculocondylar syndrome, 602483). The author published photographs of the single case reported by Fumiiri and Hyakusoku (1983), with a unilateral ear defect that exhibited near identity to the previously depicted cases.

Al-Qattan (1998) reported 2 unrelated girls with question mark ears. The first was a 5-year-old girl of Sudanese origin with a left ear deformity and a shallow 2-mm skin dimple on the posterior surface of the ear, who had a normal-appearing eardrum and normal hearing. The second was a 5-year-old Saudi girl with bilateral question mark ears, who also had another area of helical deficiency just superior to the Darwinian tubercle on the right ear, but no skin dimples; her hearing was normal. There was no family history of ear abnormalities in either case. Al-Qattan (1998) suggested that this anomaly be designated Cosman deformity of the auricle.

Shkalim et al. (2008) reported a 3-generation family segregating question mark ears in an autosomal dominant pattern; the proband and her paternal grandfather were bilaterally affected, whereas her father had only a right-sided deformity. Affected members of this family were later found to have auriculocondylar syndrome-2 (ARCND2; 614669).

Gordon et al. (2013) studied 2 families with isolated question mark ears. In a family from Armenia ('case 11'), the mother presented with a significant notch in the border of the helix, at the lobe-helix junction, bilaterally. Her daughter displayed bilateral clefting between the lobe and helix. No overt signs of mandibular hypoplasia were evident. X-rays of the mandible of the daughter at 2 years of age did not reveal any obvious anomalies. In a family of African origin ('case 12'), the mother displayed a notch at the lobe-helix junction, and her son and daughter each had protruding helices and clefting, or constriction, between the lobe and helix. The daughter had been treated for acute lymphoblastic leukemia. The authors were not able to assess mandibular x-rays in this family, but there were no external signs of micrognathia.

Molecular Genetics

In 2 unrelated patients from families with isolated question mark ears that were previously studied by Gordon et al. (2013) and found to be negative for mutation in the coding regions of the GNAI3 (139370), PLCB4 (600810), GNAQ (600998), and GNA11 (139313) genes and the catalytic domain exons of the PLCB3 gene (600230), Gordon et al. (2013) performed whole-exome sequencing and identified heterozygosity for a missense (V64D; 131240.0004) and a nonsense (Y83X; 131240.0005) mutation in the EDN1 gene, respectively. The mutations segregated with disease in both families.