Clinical features as described above
Analysis of the carrier status in families at risk
Prenatal diagnosis in the case of confirmed carrier status of the mother
Coffin-Lowry Syndrome - RPS6KA3
CLS
Clinical Features
The Coffin-Lowry syndrome is a syndrome of mental retardation, small stature, progressive skeletal abnormalities (kyphoscoliosis, pectus carinatum or excavatum) and typical dysmorphic features. The latter include hypertelorism, antimongoloid slanting of palpebral fissures palpebral apertures, prominent eyebrows, a broad nasal root of nose, anteverted nares, prominent lower lips, prognathism, hypo- and dysodontia and large, little formed ears. Clumsy, hypotonic hands with bulbous tapering of the fingers are considered pathognomonic. The symptoms are usually more pronounced in males. In females, the phenotypic appearance of the syndrome varies considerably ranging between no abnormalities, slight dysmorphic features and retardation up to the full symptomatic picture. In general, the physical symptoms increase with age.
Genetic Information
The disease follows X-chromosomal inheritance. Symptoms are often milder in affected females (see above).
The disease is caused by alterations in the RSK2 (RPS6KA3) gene on the short arm of the X chromosome (Xp22.1-p22.2). The mutations identified so far are scattered over all 22 exons of the gene. 70% of the mutations arise de novo.
Prevalence
rare
Diagnostic
Indication
Method
Direct diagnostics:
All exons of the gene as well as the flanking regions are analyzed by sequencing.
MLPA to detect deletions and duplications
Sample Requirement
2 to 4 ml of EDTA blood
Duration
approx. 4 weeks