Trichomegaly

A number sign (#) is used with this entry because of evidence that trichomegaly (TCMGLY) is caused by homozygous mutation in the FGF5 gene (165190) on chromosome 4q21.

Clinical Features

Unusually long eyelashes is a morphologic trait which is observed in multiple relatives and has been reported in association with a variety of medical problems as indicated by Goldstein and Hutt (1972). They found it with cataract in a brother and sister who also had hereditary spherocytosis. Gray (1944), who appears to have coined the term 'trichomegaly,' reported the trait in father and daughter.

Harrison and Mullaney (1997) observed an 18-month-old girl with marked elongation of the eyelashes and corneal irritation. Her sibs also had trichomegaly. The parents stated that they regularly trimmed the children's lashes because of marked elongation. The parents and grandparents were first cousins, and all had normal lashes. Photographs of the proposita and her affected brother and sister were provided.

Higgins et al. (2014) studied 2 large consanguineous Pakistani families in which 8 and 16 individuals, respectively, had trichomegaly. In both families, hair growth was most striking in the eyelashes; however, examination of plucked forearm hairs showed that those hairs were significantly longer and showed increased variance in length, but no increase in thickness, compared to controls. Affected members of 1 family also showed mild hypertrichosis of the eyebrows as well as on the cheeks and forehead. Analysis of root tip morphology revealed a shift toward anagen morphology in patient hairs (59-65% anagen) compared to ethnically matched controls (17%).

Mapping

In a large consanguineous Pakistani family segregating autosomal recessive trichomegaly, Higgins et al. (2014) performed homozygosity mapping and identified a single region of homozygosity on chromosome 4q21.21 that was shared among affected individuals and was absent in unaffected family members.

Molecular Genetics

In 2 large consanguineous Pakistani families segregating autosomal recessive trichomegaly, Higgins et al. (2014) performed exome sequencing and identified homozygosity for a splice site and a frameshift mutation in the FGF5 gene (165190.0001 and 165190.0002, respectively) in affected individuals. The mutations, which segregated with disease in each family, were not found in 50 ethnically matched controls or in public databases. Sequencing FGF5 in unrelated probands from 5 more families with trichomegaly identified a missense mutation (Y174H; 165190.0003) in 1 proband from Pakistan.