Three M Syndrome 3

A number sign (#) is used with this entry because 3M syndrome-3 (3M3) can be caused by homozygous mutation in the CCDC8 gene (614145) on chromosome 19q13.

Description

The 3M syndrome is characterized by poor postnatal growth and distinctive facial features, including triangular facies, frontal bossing, fleshy tipped nose, and fleshy lips. Other features may include skeletal anomalies and prominent heels (summary by Hanson et al., 2011).

For a general phenotypic description and a discussion of genetic heterogeneity of 3M syndrome, see 3M1 (273750).

Clinical Features

Hanson et al. (2011) described 5 unrelated probands, all born of consanguineous Asian parents, with 3M syndrome. All had poor growth, fleshy tipped nose, short thorax, and prominent heels. More variable, but common features included anteverted nares, triangular face, dolichocephaly, frontal bossing, midface hypoplasia, long philtrum, pointed chin, prominent ears, short neck, and square shoulders. Less common features included tall vertebral bodies, slender long bones, clinodactyly, hyperlordosis, transverse chest groove, and hip dysplasia.

Molecular Genetics

By autozygosity mapping followed by exome sequencing of 3 Asian patients with 3M syndrome-3, Hanson et al. (2011) identified 2 different homozygous 1-bp duplications in the CCDC8 gene (614145.0001 and 614145.0002). Both mutations were predicted to result in truncation, consistent with a loss of function. The findings supported the hypothesis that the 3M syndrome results from defects in a pathway controlling human growth.