Overview
Alström syndrome is a rare autosomal recessive ciliopathy caused by mutations in ALMS1, characterized by cone-rod dystrophy with early childhood onset, sensorineural hearing loss, obesity, type 2 diabetes mellitus, dilated cardiomyopathy, and multi-organ fibrosis. Visual impairment is typically the presenting feature, with nystagmus and photophobia in infancy progressing to legal blindness by the second decade. It is distinguished from Bardet-Biedl syndrome by the absence of polydactyly and intellectual disability.
Genetics
Caused exclusively by ALMS1 mutations. ALMS1 encodes a centrosomal/basal body protein. Over 300 mutations identified. Autosomal recessive.
| Gene | Locus | Inheritance | Notes |
|---|---|---|---|
| ALMS1 | 2p13.1 | AR | Alström syndrome protein 1; centrosomal/basal body protein; sole known cause |
Clinical Presentation
Infancy
- Nystagmus and photophobia
- Cone-rod dystrophy onset
- Dilated cardiomyopathy (neonatal form in some)
Childhood
- Progressive vision loss
- Sensorineural hearing loss
- Obesity onset
Adolescence–adulthood
- Type 2 diabetes mellitus
- Legal blindness
- Multi-organ fibrosis (liver, kidney, lung)
Diagnosis
- ERG: Cone-rod dystrophy pattern
- Genetic testing: ALMS1 sequencing — confirms diagnosis
- Cardiac evaluation: Echocardiography for cardiomyopathy
- Metabolic evaluation: Glucose, insulin, lipid profile
- Audiological assessment: Annual hearing evaluation
Current Research & Treatment
No disease-modifying treatments approved. Management is multidisciplinary, targeting individual organ systems. The Alström Syndrome International organization coordinates research and patient support. Gene therapy for ALMS1 is in early preclinical stages.
Active Clinical Trials
The following active clinical trials are investigating treatments for Alström Syndrome. Trial status and enrollment may change; always verify directly on ClinicalTrials.gov.