Alstrom syndrome
Incidence
Alstrom syndrome is inherited as an autosomal recessive trait. Alstrom syndrome is a rare disorder described in about 80 patients worldwide. Caused by mutation in the Alstrom syndrome gene (ALMS1).
Clinical Characteristics
Alstrom syndrome is a rare genetic disorder most often characterized by vision and hearing abnormalities, childhood obesity, diabetes mellitus, and slowly progressive kidney (renal) dysfunction (chronic nephropathy). Specific features vary from case to case. Additional features sometimes associated with Alstrom syndrome include disease of the heart muscle (cardiomyopathy), skin abnormalities and abnormalities affecting additional organ systems. Intelligence is not affected. It is characterized by progressive retinal degeneration and obesity; other features appear mostly after the first decade: progressive hearing impairment, non-insulin-dependent diabetes mellitus and kidney and heart failure. Mental retardation is absent and the extremities are normal; these two features help differentiating it from Bardet-Biedl syndrome. Phenotypic expression varies considerably, even within sibships. Infantile retinal dystrophy is severe. The electroretinogram is absent or attenuated with better preserved rod than cone function. Retinal dystrophy is progressive with no light perception by 20 years of age. The retinal lesion causes nystagmus and early loss of central vision, thus this syndrome differs from other pigmentary retinopathies in which loss of peripheral vision occurs first. Obesity develops during early childhood (sometimes before age 6 months), with an advanced bone age. Congestive heart failure secondary to dilated cardiomyopathy can help for diagnosis, but is not constant. Neurosensorial hearing loss develops during the second decade, with variable intensity. Alstrom syndrome is not often identified until diabetes mellitus develops in the second or third decade, hyperglycemia coexisting with hyperinsulinism. In the late stages of the disease, affected individuals show progressive chronic nephropathy with possible kidney failure. The most frequent causes of death include renal insufficiency and cardiac failure. Hepatic dysfunction may influence prognosis as well. Manifestations observed in some patients, but not all, include acanthosis nigricans, alopecia, short stature, scoliosis, kyphosis, hyperostosis frontalis interna, muscle dystonia, and subcapsular cataract. Other metabolic and endocrinological abnormalities have been described: hypothyroidism, hypogonadism, diabetes insipidus, growth hormone deficiency, hyperuricemia and hyperlipidemia. This syndrome is autosomal recessive, due to a mutation in the ALMS1 gene, mapped to 2p13. Search for one of the several mutations identified in the ALMS1 gene may be used for a possible prenatal diagnosis after birth of an index case in a family.
Precipitants
None
Provocation Tests
None
Diagnostic Procedures
It is a clinical diagnosis. Search for one of the several mutations identified in the ALMS1 gene may be used as well.