The packet lists one gene, ALMS1, located on chromosome 2, with a ClinGen gene-disease validity classification of definitive. The packet's inheritance field lists autosomal recessive inheritance, and the GeneReviews genetic counseling section states that Alstrom syndrome is inherited in an autosomal recessive manner. According to GeneReviews, parents of an affected child are obligate heterozygotes who are asymptomatic carriers, and each sibling of an affected individual has a 25% chance of being affected at conception when both parents are carriers. The chapter reports that no males with molecularly confirmed Alstrom syndrome are known to have fathered children and no females are known to have become pregnant. GeneReviews states that genotype-phenotype correlations are difficult to draw because almost all ALMS1 pathogenic variants are null variants and most affected individuals are compound heterozygous for rare variants reported in only a few families.

GeneReviews describes the clinical diagnosis as based on cardinal features that emerge across infancy, childhood, and young adulthood, and states that the accuracy of the proposed clinical criteria is low in children before age five years, especially without infantile cardiomyopathy. Its diagnostic criteria table is organized by age range. For birth to 2 years, major criteria are one ALMS1 pathogenic variant or a family history of Alstrom syndrome, nystagmus, photophobia or impaired vision, and infantile cardiomyopathy, with obesity and sensorineural hearing loss as minor criteria. The minimum required is two major criteria, or one major plus two minor criteria.

Suggestive findings listed in GeneReviews include cone-rod dystrophy with nystagmus and light sensitivity in the first year of life, with full-field electroretinography described as abnormal from birth. Other suggestive findings include early-onset truncal obesity, progressive hearing impairment, cardiomyopathy, insulin resistance or type 2 diabetes, adult short stature, hypogonadism, declining renal function, and variable hepatic disease. Molecular testing for ALMS1 pathogenic variants figures in the age-based criteria. The packet contains no newborn screening information.

The packet certifies no FDA-approved treatment for Alstrom syndrome. Its orphan drug records include two entries with an indication of Alstrom syndrome: setmelanotide, which holds an orphan designation, and 3-pentylbenzeneacetic acid sodium salt, whose designation is withdrawn. An orphan designation is a regulatory status and does not indicate approval. The packet's orphan drug list also contains many records with unrelated indications, which are not treated here as options for this condition.

GeneReviews states that no therapy exists to prevent the progressive organ involvement of Alstrom syndrome and describes coordinated multidisciplinary care. For the retinal disease, it mentions tinted lenses for photophobia and educational planning around expected blindness. For hearing loss, it describes hearing aids, cochlear implantation in some patients, and myringotomy for recurrent otitis media. For obesity, it describes a reduced-calorie diet and regular exercise. For cardiomyopathy, it describes standard heart failure therapy in line with current guidelines, with cardiac transplantation successful in rare cases. For insulin resistance and type 2 diabetes, it describes treatment as in the general population, including lifestyle modification, metformin, and incretin analogs, with caveats where heart failure or liver dysfunction is present. These descriptions are drawn from GeneReviews.

The packet does not certify a separate natural history entry, so this section follows the GeneReviews clinical description. The condition is described as progressive across multiple organ systems. For vision, GeneReviews reports visual acuity of 6/60 or less by age ten years in affected individuals, increasing constriction of visual fields, and no light perception by age 35 years. Body weight is described as tending to normalize in some individuals after adolescence. Renal disease is described as variably progressive in all individuals. GeneReviews notes that the proportion of infants with infantile cardiomyopathy is probably underestimated because some infants succumb to heart failure before the diagnosis is made. Survival figures are not certified in the packet.

The packet certifies active ClinicalTrials.gov records associated with Alstrom syndrome. Their titles reference a cohort for Bardet-Biedl syndrome and Alström syndrome for translational research at University Hospital, Strasbourg, a rare disease patient registry and natural history study at Sanford Health, and a real-world study of MC4R agonist therapy in Bardet-Biedl syndrome and severe genetic obesity. The packet classifies the trial interventions as drug therapy, other interventions, and gene therapy, and notes that gene therapy and biomarker publications are present; study titles alone do not establish the intervention tested. The GeneReviews section on therapies under investigation describes a treatment trial of the antifibrotic agent PBI-4050 as under way at the time of the chapter. Setmelanotide appears in the packet as an orphan designation for this condition and is not presented as an approved therapy.