Clinical characteristics: COMP-related pseudoachondroplasia (COMP-PSACH) is characterized by normal length at birth and normal facies. Often the presenting feature is a waddling gait, recognized at the onset of walking. Typically, the growth rate falls below the standard growth curve by approximately age two years, leading to a moderately severe form of disproportionate short-limb short stature. Joint pain during childhood, particularly in the large joints of the lower extremities, is common. Degenerative joint disease is progressive; approximately 50% of individuals with COMP-PSACH eventually require hip replacement surgery.
Diagnosis/testing: The diagnosis of COMP-PSACH can be made on the basis of clinical findings and radiographic features. Identification of a heterozygous pathogenic variant in COMP on molecular genetic testing establishes the diagnosis if clinical features are inconclusive.
Management: Treatment of manifestations: Analgesics for joint pain; encourage physical activities that do not cause excessive wear and/or damage to the joints; osteotomy for lower limb malalignment; rarely, surgery for scoliosis; C1-C2 fixation for symptoms and radiographic evidence of cervical spine instability; attention to and social support for psychosocial issues related to short stature for affected individuals and their families.
Surveillance: Assess growth at each visit throughout childhood. Regular examinations for evidence of symptomatic joint hypermobility and/or lower limb malalignment, kyphoscoliosis, degenerative joint disease, and neurologic manifestations, particularly spinal cord compression secondary to odontoid hypoplasia. Assess for psychosocial issues annually or at each visit.
Agents/circumstances to avoid: In those with odontoid hypoplasia, extreme neck flexion and extension should be avoided.
Genetic counseling: COMP-PSACH is inherited in an autosomal dominant manner. Some individuals diagnosed with COMP-PSACH have an affected parent. A proband diagnosed with COMP-PSACH may have the disorder as the result of a de novo pathogenic variant. Each child of an individual with COMP-PSACH and a reproductive partner with normal bone growth has a 50% chance of inheriting the COMP pathogenic variant and having COMP-PSACH. Because many individuals with short stature select reproductive partners with short stature, offspring of individuals with COMP-PSACH may be at risk of having double heterozygosity for two dominantly inherited bone growth disorders. Once the COMP pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.
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