Purpose: To alert the medical community that whole exome sequencing can find accessory gene changes in well-known syndromes that alter preventive health care and management. Meaning: A collagen type VI gene change add...Purpose: To alert the medical community that whole exome sequencing can find accessory gene changes in well-known syndromes that alter preventive health care and management. Meaning: A collagen type VI gene change adds muscle weakness, hypermobility, and dysautonomia concerns to usual management considerations for Down syndrome. Methods: Commercial whole exome sequencing combined with clinical interpretation of DNA sequence change added new considerations to patient management and parental counsel. Results: An 11-year-old child with the trisomy 21 form of Down syndrome who was evaluated for extraordinary joint laxity had a heterozygous collagen type VI aspartic to glutamic acid (COL6A3 c.6360 C>G p.Asp2120Glu) gene change found by whole exome sequencing. The DNA variant was qualified as having strong relevance to the enhanced hypermobility due to prior association of collagen 6 gene changes with myopathy. Conclusions: Dual diagnosis of Ehlers-Danlos syndrome was not assigned because the patient lacked criteria like bruising, unusual scars, or selected dysautonomia symptoms. The concept of a hypermobility spectrum offers advantages for management of its constituent conditions if clinically guided ascertainment and DNA diagnostics are employed.展开更多
文摘Purpose: To alert the medical community that whole exome sequencing can find accessory gene changes in well-known syndromes that alter preventive health care and management. Meaning: A collagen type VI gene change adds muscle weakness, hypermobility, and dysautonomia concerns to usual management considerations for Down syndrome. Methods: Commercial whole exome sequencing combined with clinical interpretation of DNA sequence change added new considerations to patient management and parental counsel. Results: An 11-year-old child with the trisomy 21 form of Down syndrome who was evaluated for extraordinary joint laxity had a heterozygous collagen type VI aspartic to glutamic acid (COL6A3 c.6360 C>G p.Asp2120Glu) gene change found by whole exome sequencing. The DNA variant was qualified as having strong relevance to the enhanced hypermobility due to prior association of collagen 6 gene changes with myopathy. Conclusions: Dual diagnosis of Ehlers-Danlos syndrome was not assigned because the patient lacked criteria like bruising, unusual scars, or selected dysautonomia symptoms. The concept of a hypermobility spectrum offers advantages for management of its constituent conditions if clinically guided ascertainment and DNA diagnostics are employed.
