Anosmia, Isolated Congenital

Clinical Features

The main reason for considering anosmia separately is that it is not clear whether it is always merely part of the Kallmann syndrome (see 147950 and 308700) or a distinct disorder. Affected males reported by Glaser (1918) in which X-linked inheritance was suggested had 'excessive sex interest.' It was a Russian Jewish family like those of Kallmann et al. (1944).

Molecular Genetics

Associations Pending Confirmation

In twin brothers and a sister with congenital anosmia, born to parents of Ashkenazi-Yemenite origin, Alkelai et al. (2016) identified a c.4829C-T transition in the TENM1 gene (300588), resulting in a pro1610-to-leu (P1610L) substitution at a highly conserved residue. Sanger sequencing of the extended family revealed that the unaffected mother and maternal grandmother were carriers of the variant. The affected female and her mother had X-inactivation ratios of 28:72 and 63:37, respectively. The variant was not found in approximately 67,600 control samples. Alkelai et al. (2016) stated that additional studies were required to confirm the role of TENM1 in congenital anosmia.