Coffin-Lowry syndrome is a rare genetic disorder characterized by mental retardation; abnormalities of the head and facial (craniofacial) area; large, soft hands with short, thin (tapered) fingers; short stature; and/or various skeletal abnormalities. Characteristic facial features may include an underdeveloped upper jawbone (maxillary hypoplasia), an abnormally prominent brow, downslanting eyelid folds (palpebral fissures), widely spaced eyes (hypertelorism), large ears, and/or unusually thick eyebrows. Skeletal abnormalities may include abnormal front-to-back and side-to-side curvature of the spine (kyphoscoliosis) and unusual prominence of the breastbone (sternum) (pectus carinatum). Coffin-Lowry syndrome is caused by mutations in the RSK2 gene and is inherited as an X-linked dominant genetic trait. Males are usually more severely affected than females.
The symptoms of Coffin-Lowry syndrome tend to be more severe in males, although symptoms in affected females can range from none to the same severity seen in males. The characteristic facial features seen in affected males become more easily identifiable in late childhood and adulthood. The face is characterized by a prominent forehead and eyebrows, narrowing of both temples, scarce hair on the scalp, thickened eyebrow ridges, downslanting eyelid slits, wide-set eyes, thickened upper eyelids, a broad nasal bridge with a thick dividing cartilage (septum), thick prominent lips, an open mouth, prominent chin and ears.
Limb abnormalities may include large soft hands with double-jointed thick fingers that taper toward the tips, an unusual prominent transverse crease (hypothenar) and a shortened big toe. In males, the skin is loose and may stretch easily. Many bone abnormalities may also occur such as thickening of facial bones, shortening of the long bones, and pointed or sunken breast bone. Abnormal front-to-back and side-to-side curvature of the spine may also be present (kyphosis and scoliosis) and progresses with age. Affected individuals usually have short stature. A smaller than average head size (microcephaly) and dental abnormalities are common. Hearing loss is sometimes associated with Coffin-Lowry syndrome. In rare cases, vision loss may occur. Heart problems may be present and can be life threatening.
Affected males may have severe to profound mental retardation. Intelligence in affected females ranges from normal to profound mental retardation. Severely affected children may have no speech development.
Some affected individuals experience episodes of brief collapse without loss of conciousness (drop attacks) that occur following an unexpected noise or emotional event.
Coffin-Lowry syndrome is caused by changes (mutations) in the RSK2 and RPS6KA3 gene on the X chromosome and has been mapped to Xp22.2-p22.1. Some individuals with Coffin-Lowry syndrome do not have a detectable mutation in the RSK2 gene.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered 1-22 and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further subdivided into many bands that are numbered. For example, “chromosome Xp22.2-p22.2” refers to band 22.2-22.1 on the short arm of the X chromosome. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Coffin-Lowry syndrome is inherited as an X-linked dominant genetic trait. About 70-80% of those affected have no family history of the condition. Males with an RSK2 gene mutation will be affected with Coffin-Lowry syndrome and females with an RSK2 gene mutation have a high risk for developmental delay and mild physical symptoms of the disease.
Coffin-Lowry syndrome affects as many males as females. However, symptoms may be more severe in males.
X-ray and neuroimaging studies may be helpful in confirming a diagnosis of Coffin-Lowry syndrome. Decreased ribosomal S6 kinase activity in cultured fibroblast or transformed lymphoblast cells from a male indicates Coffin-Lowry syndrome. Studies of enzyme activity can not be used to diagnose an affected female.
Molecular genetic testing on a blood specimen or cells from a cheek swab is available to identify mutations in the RSK2 gene. This testing can be used to confirm but not rule out the diagnosis of Coffin-Lowry syndrome because not all affected individuals have a detectable mutation.
Treatment for Coffin-Lowry syndrome is symptomatic and supportive. Affected individuals should have regular cardiac, hearing and visual examinations. Patients should be monitored for progressive kyphoscoliosis which can be life threatening if the cardiorespiratory system becomes compromised. Antiepileptic medications such as clonazepam may be used to treat drop attacks.
Genetic counseling will be helpful for patients and their families.
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