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Coffin-Lowry Syndrome.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2016.
2002 Jul 16 [updated 2014 Mar 27].

Excerpt

CLINICAL CHARACTERISTICS:

Coffin-Lowry syndrome (CLS) is usually characterized by severe-to-profound intellectual disability in males; less severely impaired individuals have been reported. Intellect ranges from normal to profoundly impaired in heterozygous females. The facial appearance is characteristic in the affected, older male child or adult. The hands are short, soft, and fleshy, often with remarkably hyperextensible fingers that taper from wide (proximally) to narrow with small terminal phalanges and nails. Males are consistently below the third centile in height. Microcephaly is common. Cardiac abnormalities may be present and can contribute to premature death. Stimulus-induced drop attacks (SIDAs) in which unexpected tactile or auditory stimuli or excitement triggers a brief collapse but no loss of consciousness are present in approximately 20% of affected individuals. Typically SIDAs begin between mid-childhood and the teens. Progressive kyphoscoliosis is one of the most difficult aspects of long-term care. Life span may be reduced.

DIAGNOSIS/TESTING:

The diagnosis of CLS is established in males with severe developmental delay, characteristic craniofacial and hand findings, and radiographic findings. Carrier females may be mildly affected. Molecular genetic testing of RPS6KA3, the only gene yet published in which pathogenic variants are known to cause CLS, can be used to confirm but not to rule out the diagnosis of typical CLS. Sequence analysis identifies pathogenic variants in approximately 25%-40% of clinically diagnosed probands.

MANAGEMENT:

Treatment of manifestations: SIDAs are treated with medications such as valporate, clonazepam, or selective serotonin uptake inhibitors; individuals who experience frequent SIDAs may require use of a wheelchair and should be protected, if possible, from being startled. Risperidone may be of benefit to individuals who display destructive or self-injurious behavior. Feeding difficulties, abnormal growth velocity, behavioral problems, kyphoscoliosis, and obesity, if present, are treated in a standard manner. Prevention of secondary complications: Intervention to prevent progression of kyphoscoliosis to the point of cardio-respiratory compromise. Surveillance: Periodic hearing, dental, and vision examinations; annual clinical cardiac examination, adding an echocardiogram by age ten years and repeating every five to ten years; regular monitoring of the spine for progressive kyphoscoliosis. Agents/circumstances to avoid: Individuals who experience SIDAs should be protected as much as possible from being startled and/or from falls.

GENETIC COUNSELING:

CLS is inherited in an X-linked manner. Approximately 70%-80% of probands have no family history of CLS, and 20%-30% have more than one additional affected family member. Children of a woman known to be a carrier are at 50% risk of inheriting the pathogenic variant. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers and at high risk for at least some developmental delay and mild physical signs of CLS. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible in families in which the pathogenic variant has been identified in an affected family member or in which linkage studies can exclude the X chromosome that carries (or potentially carries) the pathogenic variant.

Copyright © 1993-2016, University of Washington, Seattle. All rights reserved.

PMID:
20301520
[PubMed]
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