Anosmia, Isolated Congenital

Clinical Features

In a Japanese kindred, Yamamoto et al. (1966) found tremor and/or anosmia or hyposmia in 14 persons. They suggested that the 2 traits are independent dominants. Their findings may be equally consistent with the pleiotropic and variable effects of a single gene.

In the Faroe Islands, Lygonis (1969) found a large kindred in which 9 males and 19 females in 4 generations had anosmia with no other abnormality.

Singh et al. (1970) observed anosmia in 6 males in 3 consecutive generations. One male who transmitted the trait had only partial anosmia.

Assouline et al. (1998) reported 2 patients with isolated congenital anosmia, a 15.5-year-old girl and an 11-year-old boy. In both patients, bilateral aplasia of the olfactory bulbs was demonstrated by cranial magnetic resonance imaging.

One of the patients of Hockaday (1966) with anosmia-hypogonadism had father and a brother with anosmia alone. Some family members of patients with Kallmann syndrome (see Pitteloud et al., 2006 and 147950) have been found to have isolated congenital anosmia.

Inheritance

Dominant inheritance was recorded by Mainland (1945), Joyner (1963), and Lygonis (1969). Several instances of male-to-male transmission were observed.

Mapping

Ghadami et al. (2004) performed genomewide linkage analysis in 2 unrelated Iranian families in which a total of 54 members were available for study and 7 of them had isolated congenital anosmia. In both families, the trait appeared to be inherited as an autosomal dominant with incomplete penetrance. By 2-point linkage analysis, a maximum lod score of 5.14 (recombination fraction theta = 0.00), with penetrance of 0.8, was found at marker D18S1108. Haplotype analysis showed that all affected individuals shared a common haplotype in the 18p11.23-q12.2 region. All exons and exon-intron boundaries of 8 candidate genes were sequenced but no mutations were found in any affected family members.