Alstrom syndrome is characterized by cone-rod dystrophy, obesity, progressive sensorineural hearing impairment, dilated or restrictive cardiomyopathy, the insulin resistance syndrome, and multiple organ failure. Wide clinical variability is observed among affected individuals, even within the same family. Cone-rod dystrophy presents as progressive visual impairment, photophobia, and nystagmus usually starting between birth and age 15 months. Many individuals lose all perception of light by the end of the second decade, but a minority retain the ability to read large print into the third decade. Children usually have normal birth weight but develop truncal obesity during their first year. Progressive sensorineural hearing loss presents in the first decade in as many as 70% of individuals. Hearing loss may progress to the severe or moderately severe range (40-70 db) by the end of the first to second decade. Insulin resistance is typically accompanied by the skin changes of acanthosis nigricans, and proceeds to type 2 diabetes in the majority by the third decade. Nearly all demonstrate associated dyslipidemia. Other endocrine abnormalities can include hypothyroidism, hypogonadotropic hypogonadism in boys, and polycystic ovaries in girls. More than 60% of individuals with Alstrom syndrome develop cardiac failure as a result of dilated or restrictive cardiomyopathy. About 50% of individuals have delay in early developmental milestones; intelligence is normal. Liver involvement includes elevation of transaminases, steatosis, hepatosplenomegaly, and steatohepatitis. Portal hypertension and cirrhosis can lead to hepatic encephalopathy and life-threatening esophageal varices. Pulmonary dysfunction and severe renal disease may also develop. End-stage renal disease (ESRD) can occur as early as the late teens.
The diagnosis of Alstrom syndrome is based on clinical findings. Molecular genetic testing of ALMS1, the only gene in which mutations are known to cause Alstrom syndrome, is estimated to detect mutations in 70%-80% of individuals of northern European descent, and approximately 40% world-wide.
Alstrom syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutations have been identified in an affected family member.