Marshall-Smith Syndrome
Marshall-Smith syndrome (not to be confused with "Marshall" Syndrome which is very different), or accelerated skeletal maturation-facial dysmorphism-failure to thrive syndrome, is a rare genetic disease characterized by unusually quick maturation (physical growth and bone development) and failure to thrive. The quick maturation results to a tall stature and advanced bone age at birth, and failure to thrive results in being underweight relative to height.
The disorder is present at birth affecting males and females in equal numbers. Symptoms are varied and usually present before birth, mainly respiratory difficulties, mental retardation, and certain physical characteristics. The respiratory difficulties are common and usually the main cause of death at birth whereas the intellectual disability becomes apparent if the baby survives infancy. Physical characteristics include excessive hair growth, a long head with a prominent forehead, prominent or bulging eyes, receding chin, and/or an upturned nose with a low nasal bridge.
Other patients diagnosed with the disorder show defects in the immune system, brain abnormalities such as cerebral atrophy, larger than normal convolutions of the cerebral cortex, or an absent corpus callosum. In other cases, the leaf-shaped structure in the throat which normally prevents food or liquid from passing into the windpipe may not develop properly, absent or smaller than normal openings leading from the nasal passages into the post-nasal space, an abnormal larynx and/or soft cartilage of the larynx, or a short breastbone may occur.
The exact cause of Marshall-Smith Syndrome is unknown. There is no evidence that it is genetic or hereditary but the sporadic and rare occurrence suggests a de novo dominant mutation, meaning that the disorder occurs for the first time in a family due to mutation in either ovum, sperm or the fertilized egg itself during early embryogenesis.
Treatment of Marshall-Smith Syndrome is symptomatic and supportive. Aggressive treatment of breathing difficulties is necessary. Most patients die by 20 months of age while the oldest reported patient is 15 years. Cause of death is generally related to pulmonary and central nervous system problems. The prognosis is poor and the disorder is usually fatal within the first years of life. A few cases of prolonged survival have been reported in patients without respiratory complications and are associated with intellectual deficit.
Similar disorders include Weaver Syndrome where growth and bone maturation also occur faster than normal but patients have normal to above normal weight in relative to height. Gigantism occurs before puberty, is caused by over-secretion of growth hormone and characterized by excessive growth during childhood with relatively normal body proportions and sexual development. Soto’s Syndrome, rare but hereditary disorder characterized by excessive growth during the first 4 to 5 years of life. McCune-Albright Syndrome is characterized by early sexual development, change in bone integrity which produces pain, increasing deformity and disability, and possible changes in skin pigmentation. This syndrome involves the endocrine, muscle and bone systems.