Coffin Lowry Syndrome

Definition

Coffin-Lowry syndrome (CLS) is an inherited syndrome characterized by mental retardation, slow growth, distinctive facial appearance, large soft hands, loose joints, minor skeletal changes, and low muscle tone (hypotonia). Full expression of the disorder is seen only in males, although females may have some of the physical features and learning disability.

Description

Coffin-Lowry syndrome is one of a large number of mental retardation syndromes caused by abnormalities (mutations) of genes on the X chromosome. The pattern of physical findings, combined with mental retardation, makes the condition readily recognizable and its frequency makes it one of the well-known X-linked mental retardation syndromes. Although CLS was initially considered to be two separate syndromes, Coffin syndrome and Lowry syndrome, the two entities were recognized as the same disease in 1975.

Genetic profile

The gene for Coffin-Lowry syndrome, RSK2, is located on the short arm of the X chromosome designated as Xp22. Mutation of the RSK2 gene leads to full expression of the Coffin-Lowry syndrome in males since they only have a single X chromosome. If one of the two RSK2 genes is altered, it leads to some expression of the condition in the form of physical features and learning disabilities. Because females have two X chromosomes, CLS is considered inherited as an X-linked semidominant.

Demographics

Coffin-Lowry syndrome appears to occur in all populations. The full syndrome is seen in males with lesser expression in carrier females. A prevalence range of one in 50,000-100,000 males has been cited, but no studies with complete case findings have been conducted.

Signs and symptoms

Although the findings in Coffin-Lowry change with age, some manifestations are present from birth. Low muscle tone (hypotonia) and distinctive facial features that include prominent forehead, increased space between the eyes, forward direction of the nostrils, arching of the upper lip, and simple ear structure may be present in infancy. With the passing years, the face elongates, the ears become notably large, the lips and nasal structures thicken, and the mouth is usually open and agape. The hands are large and soft with thick fingers that narrow at their ends. There is generalized looseness at the joints. The central part of the chest may bow outward, the knees are flexed, and the feet flat.

Growth is slow, as manifest by low birth weight, a small head, and short stature during childhood and adult life. All developmental milestones in infancy and childhood are delayed, and intellectual function is severely impaired.

Milder findings consisting of short stature, increased space between the eyes, thick nasal tissues, prominent lips, and soft fleshy hands with thick fingers are consistently seen in carrier females. Intellectual function may be normal or mildly impaired.

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Author Info: Roger E. Stevenson MD, Thomson Gale, Gale, Detroit, Gale Encyclopedia of Genetic Disorders Part II, 2005

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