A syndrome of mental retardation and
osteocartilaginous abnormalities with peculiar facies.
Coffin-Siris-Wegienka Syndrome (do not confuse with
Coffin-Siris Syndrome, which is a different disease); Soft Hands Syndrome.
First described by Grange S. Coffin, an American
pediatrician, Evelyn Siris, an American radiologist, and Laurence C.
Wegienka, an American physician, in 1966. However, to avoid (further)
confusions with Coffin-Siris Syndrome, it was decided to name the
syndrome described here as Coffin Lowry Syndrome (after Robert Bryan Lowry,
a British medical geneticist, who described a fourth family with the same
findings in 1971).
1:50,000-100,000 live births. No sexual predilection, but
the disease is more severe in males.
X-linked semidominant inherited disorder
caused by mutations in the gene coding for the RSK2 (ribosomal s6 kinase 2),
a growth factor-regulated serine-threonine protein kinase (involved in
promotion of mitosis and activation of genes) that has been mapped to
Xp22.2-p22.1. However, research shows that only a minority of patients with this
disorder actually have a mutation in the RSK2 gene.
Abnormal proteodermatan sulfate, glycolipid-like
lysosomal granules, and vacuoles have been found in cultured skin
fibroblasts. Accumulation of hyaluronate and hyperprolinemia have been
reported in some patients.
Based on the clinical association of growth and
psychomotor retardation with hypotonia, progressive skeletal deformations,
characteristic facial dysmorphism, and large soft hands.
There is a wide variability in the expression of
the features of the syndrome. Involvement of the head and neck can present
as thickened calvarium, small sinuses paranasales, flat occiput, delayed
suture closure with large anterior fontanelle, prominent supraorbital ridges
with bushy brows, downwardly slanted palpebral fissures, hypertelorism,
blepharoptosis, large and prominent ears, large nose with broad base and
elongated philtrum, mandibular prognathism, maxillary/midfacial hypoplasia,
large mouth with big lips, and longitudinally furrowed tongue with a dorsal
groove. The facial features are generally not present at birth, but become
apparent by the second year of life, after which they become more
pronounced. Dental anomalies are numerous and may include congenital absence
of some teeth, delayed eruption, enamel hypoplasia, caries, early loss of
teeth, abnormal size and shape, malposition, malalignments, and periodontal
disease. Involvement of the musculoskeletal system presents as short thorax,
bifid sternum, pectus excavatum or carinatum, vertebral dysplasia, kyphosis,
scoliosis, delayed bone age, ligamental calcifications, hyperextensible
joints, muscle atrophy, large and soft hands with simian crease, and
tapering of the fingers. Cardiovascular involvement is frequent, with
features including atrial septal defects, persistent ductus arteriosus,
valvular anomalies (mitral valve prolapse, mitral regurgitation, tricuspid
insufficiency), impaired cardiac function, right ventricular hypertrophy,
restrictive cardiomyopathy, endomyocardial fibroelastosis, and ventricular
arrhythmias. Central nervous system features consist of generalized
hypotonia, which may be the earliest presenting sign and related to
paroxysmal drop attacks (cataplexy or hyperexplexia). In addition, seizures,
hydrocephalus, agenesis of the corpus callosum, abnormal gyration, faulty
cortical lamination, calcification of the falx cerebri, sensorineural
hearing loss, mental retardation, a tendency to obsessive-compulsive
behavior, and cervical radiculopathy ...