Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

Noonan-Like Syndrome With Loose Anagen Hair [Q87.0]

OMIM numbers: 607721, 602775 (SHOC2)

Dr. rer. biol. hum. Soheyla Chahrokh-Zadeh

Scientific Background

The Noonan-like syndrome with loose anagen hair has a phenotype similar to the Noonan syndrome: facial dysmorphia, cognitive deficit, congenital cardiac defect, sometimes accompanied by characteristic ectodermal abnormalities. In these patients, short stature arises from growth hormone deficiency. Main characteristic is little, loose, slow-growing and thin hair during the anagen phase without inner or outer root sheath, similar to the loose anagen hair syndrome. Most affected patients have darkly pigmented skin with eczema or ichthyosis. Other ectodermal abnormalities are sparse eyebrows or dystrophic or thin nails.

A single base exchange (c.4A>G) in the SHOC2 gene (soc-2 suppressor of clear homolog (C. elegans)) was detected in every patient with Noonan-like syndrome with loose anagen hair who has been examined so far. This exchange leads to amino acid substitution of serine to glycine in position 2 (p.Ser2Gly) in the respective protein (leucine-rich repeat protein SHOC-2) and is a gain-of-function mutation.

The SHOC2 gene product encodes a scaffold protein which positively modulates the RAS/MAPK signal transduction pathway. Usually, the SHOC2 protein is situated in the cell nucleus and cytoplasm; the aberrant variant is erroneously targeted to the plasma membrane.