MedGen

COL1A1/2 osteogenesis imperfecta (COL1A1/2-OI) is characterized by fractures with minimal or absent trauma, variable dentinogenesis imperfecta (DI), and, in adult years, hearing loss. The clinical features of COL1A1/2-OI represent a continuum ranging from perinatal lethality to individuals with severe skeletal deformities, mobility impairments, and very short stature to nearly asymptomatic individuals with a mild predisposition to fractures, normal dentition, normal stature, and normal life span. Fractures can occur in any bone but are most common in the extremities. DI is characterized by gray or brown teeth that may appear translucent, wear down, and break easily. COL1A1/2-OI has been classified into four types based on clinical presentation and radiographic findings. This classification system can be helpful in providing information about prognosis and management for a given individual. The four more common OI types are now referred to as follows: Classic non-deforming OI with blue sclerae (previously OI type I). Perinatally lethal OI (previously OI type II). Progressively deforming OI (previously OI type III). Common variable OI with normal sclerae (previously OI type IV). [from GeneReviews]

COL1A1/2 osteogenesis imperfecta (COL1A1/2-OI) is characterized by fractures with minimal or absent trauma, variable dentinogenesis imperfecta (DI), and, in adult years, hearing loss. The clinical features of COL1A1/2-OI represent a continuum ranging from perinatal lethality to individuals with severe skeletal deformities, mobility impairments, and very short stature to nearly asymptomatic individuals with a mild predisposition to fractures, normal dentition, normal stature, and normal life span. Fractures can occur in any bone but are most common in the extremities. DI is characterized by gray or brown teeth that may appear translucent, wear down, and break easily. COL1A1/2-OI has been classified into four types based on clinical presentation and radiographic findings. This classification system can be helpful in providing information about prognosis and management for a given individual. The four more common OI types are now referred to as follows: Classic non-deforming OI with blue sclerae (previously OI type I). Perinatally lethal OI (previously OI type II). Progressively deforming OI (previously OI type III). Common variable OI with normal sclerae (previously OI type IV). [from GeneReviews]

Multiple synostoses syndrome-4 is characterized by fusion of carpal and tarsal bones, as well as conductive hearing loss (Terhal et al., 2018). For a general phenotypic description and a discussion of genetic heterogeneity of multiple synostoses syndrome, see SYNS1 (186500). [from OMIM]

Otosclerosis is a hearing disorder that is associated with disordered bone remodeling in the otic capsule. The bone remodeling can result in conductive, mixed, or sensorineural hearing loss as a result of stapes footplate fixation or cochlear involvement (summary by Schrauwen et al., 2011). [from OMIM]

Clinical otosclerosis, the single most common cause of hearing impairment, is characterized by isolated endochondral bone sclerosis of the labyrinthine capsule. Otosclerotic foci invade the stapediovestibular joint (oval window) and interfere with free motion of the stapes. Mean age of onset is in the third decade and 90% of affected persons are under 50 years of age at the time of diagnosis. Approximately 10% of affected persons develop profound sensorineural hearing loss across all frequencies (summary by Tomek et al., 1998). Genetic Heterogeneity of Otosclerosis The locus associated with otosclerosis-1 (OTSC1) has been mapped to chromosome 15q26.1. Other loci associated with otosclerosis include OTSC2 (605727) on chromosome 7q; OTSC3 (608244) on chromosome 6p; OTSC4 (611571) on chromosome 16q; OTSC5 (608787) on chromosome 3q22-q24; OTSC7 (611572) on chromosome 6q13; OTSC8 (612096) on chromosome 9p13.1-q21.11; and OTSC10 (615589) on chromosome 1q41-q44. OTSC11 (620576) is caused by mutation in the FOXL1 gene (603252) on chromosome 16q24. OTSC12 (620792) is caused by mutation in the SMARCA4 gene (603254) on chromosome 19p13. The symbols OTSC6 and OTSC9 were reserved by the HUGO Gene Nomenclature Committee on January 30, 2003 and February 10, 2009, respectively, for as yet unpublished loci for otosclerosis. [from OMIM]