Alstrom syndrome

Alstrom syndrome is a multisystem disorder that affects multiple organs including the eyes, ears, heart, liver, kidneys, and metabolic systems. It is caused by pathogenic variants in the ALMS1 gene and follows an autosomal recessive inheritance pattern, meaning that an affected individual receives a defective copy from each parent. The condition is characterized by vision impairment from cone-rod dystrophy, sensorineural hearing loss, metabolic abnormalities such as obesity and insulin resistance, and cardiac involvement such as dilated cardiomyopathy, among other features. Although Alstrom syndrome is rare, affecting approximately 1 to 9 individuals per million, outcomes vary and management strategies continue to evolve with modern care.

The clinical presentation of Alstrom syndrome is multisystem. Ocular features include visual impairment, attenuation of retinal blood vessels, retinal dystrophy, and photophobia, while auditory involvement typically manifests as sensorineural hearing impairment that may progress over time. Metabolic disturbances are a core aspect, with nearly all affected individuals experiencing hyperglycemia, elevated hemoglobin A1c, and insulin resistance; additional findings such as obesity, hyperlipidemia, hypertriglyceridemia, and acanthosis nigricans are also common. Other features include short stature, dilated cardiomyopathy, otitis media, recurrent pneumonia, pes planus, and hyperostosis frontalis interna. Not all individuals experience every feature, and severity varies considerably across affected individuals.

Alstrom syndrome is caused by pathogenic variants in the ALMS1 gene. The function of the ALMS1 protein is critical for normal cellular processes, and disruption of this gene leads to the multisystem manifestations seen in the condition. The disorder is inherited in an autosomal recessive pattern, which means that both parents must carry a copy of the mutation for their child to be affected. This inheritance pattern also implies that, while the recurrence risk for each pregnancy remains 25%, the condition is more common when parents share a common ancestor.

Currently, management of Alstrom syndrome focuses on supportive care and symptom management, with treatment tailored to the individual’s needs. As there are no FDA-approved treatments specific to this condition, care typically involves a multidisciplinary team to address the various organ systems affected. Regular surveillance is an essential part of long-term care, including scheduled ophthalmologic examinations, audiology assessments, cardiac monitoring, and metabolic evaluations to detect complications early. Genetic counseling is recommended for affected individuals and their families, and patients should discuss treatment options with their healthcare team to determine the best approach for their situation.

The long-term outlook for individuals with Alstrom syndrome is highly variable, and outcomes depend on factors such as the severity of symptoms, age at diagnosis, and access to specialized care. With current standards of care, many individuals experience stabilization of symptoms through early intervention and regular surveillance, although the condition may progress for some over time. Outcomes described in medical literature continue to evolve as standards of care improve, and families often find it helpful to connect with specialists experienced in managing multisystem disorders. Genetic counseling and support from patient organizations can provide valuable guidance and resources as part of ongoing care.

There are clinical trials currently underway exploring new treatment approaches for Alstrom syndrome. Individuals interested in emerging therapies are encouraged to search ClinicalTrials.gov or consult their healthcare team regarding eligibility and participation in research studies.