KBG syndrome is a very rare genetic disorder characterized by short stature, moderate to severe degrees of mental retardation, developmental abnormalities of the limbs, bones of the spine (vertebrae), extremities, and/or underdevelopment of the bones of the skeleton. Abnormalities of the head and face (craniofacial dysmorphism) and malformations of the teeth and jaws (dento- skeletal dysplasia) may also be present. The exact cause of KBG syndrome is unknown, but most cases are believed to be autosomal dominant traits with variable degree of penetrance.
Children with KBG syndrome may display characteristic physical abnormalities of the head and face (craniofacial dysmorphism). Fibrous joints (coronal sutures) between certain cranial bones of the skull may close prematurely; as a result, the head may appear unusually broad, short, and/or rounded. Characteristic facial features may include eyes that appear widely spaced (telecanthus) or crossed (strabismus); wide, bushy eyebrows; and/or thin, bow-shaped lips. Characteristic features may also include abnormally large teeth in comparison to the jaws (macrodontia); jagged, crowded, or misaligned teeth; and/or unusually short, flattened, supporting bones or sockets of the jaw (mandible) that house the teeth (alveolar ridges).
A child with KBG syndrome may also be of short stature, have speech and hearing impairments, and/or have mild to severe levels of mental retardation. In some cases, mental retardation may be attributed to a small head in relation to the rest of the body (microcephaly). Affected individuals may also display abnormal bone development (skeletal dysplasia) such as malformations of the bones of the spine (vertebrae); the shortened middle portion of the thigh bones (femoral neck); abnormally developed hip bones (hip dysplasia); and/or shortened, hollow finger bones (metacarpals).
In some cases, associated features may include a sunken, pushed-in appearance of the chest (pectus excavatum or “funnel chest”); webbing or fusion of the middle toes (syndactyly); a single deep crease across the palms of the hands (simian crease); and/or six fingers or toes on one limb (hexadactyly). The number and severity of these symptoms vary widely among affected individuals.
Most cases of KBG syndrome are thought to be inherited as an autosomal dominant trait with variable degree of penetrance. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.
Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.
Variable or incomplete penetrance means that some individuals who inherit the gene for a dominant disorder will not be affected or be only mildly affected with the disorder. In some cases, KBG syndrome may also be caused by spontaneous and random (sporadic) genetic changes (mutations) that occur for unknown reasons. These mutations would then be passed on as autosomal dominant traits.
KBG syndrome is a very rare disorder that affects males and females; however, documented cases have shown a higher percentage of occurrence in males. Fewer than 20 cases have been reported in the medical literature. Characteristic symptoms are usually evident at birth (congenital). The first case of KBG syndrome was described in 1975.
KBG syndrome may be detected at birth based on typical physical findings such as skeletal abnormalities and characteristic facial and dental features. Orthopedic surgery may be particularly helpful to correct hip and spine abnormalities of affected individuals. Hearing aids, speech therapy, and comprehensive dental care may also be beneficial.
A supportive team approach for children with KBG syndrome as well as genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 148050; Last Update:7/10/00.
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