NOONAN SYNDROME-LIKE DISORDER WITH LOOSE ANAGEN HAIR

PPP1CB, SHOC2

Category:

Description

Scientific background

Noonan-like syndrome with loose anagen hair is associated with a phenotype resembling Noonan syndrome: facial dysmorphia, cognitive deficits, congenital heart defects, and others, accompanied by characteristic ectodermal anomalies. In this group of patients, short stature is caused by growth hormone deficiency. The main feature is easily extensible, sparse, thin, and slow growing hair during the anagen phase without inner and outer root sheath, similar to the loose anagen hair syndrome. Most affected individuals have dark pigmented skin with eczema or ichthyosis. Other ectodermal abnormalities include sparse eyebrows and dystrophic or thin nails.

 

Most patients with Noonan syndrome-like disorder with loose anagen hair type 1 were found to have a single base exchange (c.4A>G) in the SHOC2 gene (soc-2 suppressor of clear homolog (C. elegans)) which leads to an amino acid exchange from serine to glycine at position 2 in the corresponding protein (leucine-rich repeat protein SHOC-2) (p.Ser2Gly). This is a so-called “gain-of-function” variant. Rarely, other variants in this gene have also been described. The SHOC2 gene product encodes a scaffold protein that positively modulates the Ras/MAPK signal transduction pathway. Normally, the SHOC2 protein is located in the nucleus and cytoplasm but the aberrant variant is misdirected to the plasma membrane.

 

Noonan syndrome-like disease with loose anagen hair type 2 is caused by pathogenic variants in the PPP1CB gene. In this case, most patients show Noonan syndrome-like symptoms and hair abnormalities. In addition, most patients have been described with macrocephaly and heart defects.

 

References

Bertola et al. 2017 Am J Med Genet 173A: 824 / Gripp et al. 2016 Am J Med Genet 170A:2237 / Aoki et Matsubara 2013, Int J Hematol 97:30 / Hoban et al. 2012, Am J Med Genet 158A:1411 / Komatsuzaki et al. 2010, J Hum Genet 55:801 / Cordeddu et al. 2009, Nat Genet 41:1022

GENES

PPP1CB, SHOC2

ASSOCIATED TESTS

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