COFFIN-LOWRY SYNDROME

RPS6KA3

Description

scientific background

Coffin-Lowry syndrome (CLS) is an X-linked dominant inherited syndrome; the incidence is estimated to be between 1:50,000 and 1:100,000. The leading symptoms in males are intellecutal disability (IQ 15-60) and a characteristic appearance. The external features are a prominent forehead, wide set eyes, downward slanting eyelidfoldss, broad nose with everted nasal base, full lips with evverted lower lip, hyperextensible hand and finger joints, broad tapering fingers. In infancy and childhood, muscle hypotonia is also a prominent feature. The final height is usually below the third percentile. 80% of affected individuals develop progressive kyphoscoliosis, sometimes with cardiovascular complications, and many have a funnel (sunken) or pigeon chest. In addition, about 15% show mitral regurgitation and about 30% have sensorineural hearing loss. Seizures occur in about 5%, and drop attacks, a sudden loss of tone without loss of awareness to auditory or tactile stimuli, occur in about 20%. Females are usually more mildly affected, and the spectrum of symptoms can range from mild symptoms with normal intelligence to complete penetrance as seen in the male sex, depending on X inactivation.

 

CLS is caused by variants in the RPS6KA3 gene on the short arm of the X chromosome (Xp22.1-22.2). The gene encodes a serine-threonine kinase. Germ cell mosaics have been described.

 

References

Rogers and Abidi. 2002 Jul 16 [updated 2018 Feb 1]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2021 / Pereira et al. 2010, Eur J Hum Genet 18:627 / Pereira et al. 2007, Hum Genet 122:541 / Horn et al. 2001, Prenat Diagn 21:881 / Field et al. 2006, Clin Genet 70:509 / Delaunoy et al. 2006, Clin Genet 70:161 / Hunter 2002, Am J Med Genet 111:345 / Hanauer et al. 2002, J Med Genet 39:705 / Trivier et al. 1996, Nature 384:567

 

GENES

RPS6KA3
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