Information on the following diseases can be found in the Related Disorders section of this report:

• Borjeson syndrome
• Alpha-thalassemia mental retardation syndrome
• Williams syndrome.

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.
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Coffin-Lowry syndrome affects as many males as females. However, symptoms may be more severe in males.

Symptoms of the following disorder can be similar to those of Coffin-Lowry syndrome. Comparisons may be useful for a differential diagnosis:

Borjeson syndrome is a rare genetic disorder primarily characterized by an unusual facial appearance, mental retardation, obesity, seizures, delayed sexual development, and/or poor muscle tone (hypotonia). The disorder is transmitted as an X-linked recessive trait and therefore is usually fully expressed in males only. However, females who carry a single copy of the disease gene (heterozygous carriers) may manifest certain, usually more variable features of the disorder. (For more information on this disorder, choose "Borjeson" as your search term in the Rare Disease Database.)

Alpha-thalassemia mental retardation syndrome is an X-linked recessive genetic disorder characterized by mental retardation with short stature, microcephaly, abnormal head shape and facial features that include low muscle tone, widely spaced eyes, small nose, open mouth and prominent lips. Generalized low muscle tone and genital abnormalities may be present.

Williams syndrome is a rare genetic disorder characterized by growth delays before and after birth (prenatal and postnatal growth retardation), short stature, varying levels of mental deficiency, and distinctive facial abnormalities that typically become more pronounced with age. Characteristic facial features may include a round face, full cheeks, thick lips, a large mouth that is usually held open, and a broad nasal bridge with nostrils that flare forward (anteverted nares). Affected individuals may also have unusually short eyelid folds (palpebral fissures), flared eyebrows, a small lower jaw (mandible), and prominent ears. Dental abnormalities may also be present including abnormally small, underdeveloped teeth (hypodontia) with small, slender roots. Individuals with Williams syndrome have a deletion of 17 genes on chromosome 7. (For more information on this condition, choose "Williams" as your search term in the Rare Disease Database.)
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Diagnosis
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
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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www.centerwatch.com

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