Stickler syndrome Health Article

Definition

Stickler syndrome is a disorder caused by a genetic malfunction in the tissue that connects bones, heart, eyes, and ears.

Description

Stickler syndrome, also known as hereditary arthroophthalmopathy, is a multisystem disorder that can affect the eyes and ears, skeleton and joints, and craniofacies. Symptoms may include myopia, cataract, and retinal detachment; hearing loss that is both conductive and sensorineural; midfacial underdevelopment and cleft palate; and mild spondyloepiphyseal dysplasia and/or arthritis. The collection of specific symptoms that make up the syndrome were first documented by Stickler et al., in a 1965 paper published in Mayo Clinic Proceedings titled "Hereditary Progressive Arthro-Opthalmopathy." The paper associated the syndrome's sight deterioration and joint changes. Subsequent research has redefined Stickler syndrome to include other symptoms.

Genetic profile

Stickler syndrome is associated with mutations in three genes: COL2A1 (chromosomal locus 12q13), COL11A1 (chromosomal locus 1p21), and COL11A2 (chromosomal locus 6p21). It is inherited in an autosomal dominant manner. The majority of individuals with Stickler syndrome inherited the abnormal allele from a parent, and the prevalence of new gene mutations is unknown. Individuals with Stickler syndrome have a 50% chance of passing on the abnormal gene to each offspring.

The syndrome can manifest itself differently within families. If the molecular genetic basis of Stickler syndrome has been established, molecular genetic testing can be used for clarification of each family member's genetic status and for prenatal testing.

A majority of cases are attributed to COL2A1 mutations. All COL2A1 mutations known to cause Stickler syndrome result in the formation of a premature termination codon within the type-II collagen gene. Mutations in COL11A1 have only recently been described, and COL11A2 mutations have been identified only in patients lacking ocular findings.

Although the syndrome is associated with mutations in the COL2A1, COL11A1, and COL11A2 genes, no linkage to any of these three known loci can be established in some rare cases with clinical findings consistent with Stickler syndrome. It is presumed that other, as yet unidentified, genes mutations also account for Stickler syndrome.