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Autosomal dominant brachyolmia in a large Swedish family: Phenotypic spectrum and natural course
Author(s) -
Grigelioniene Giedre,
Geiberger Stefan,
Horemuzova Eva,
Moström Eva,
Jäntti Nina,
Neumeyer Lo,
Åström Eva,
Nordenskjöld Magnus,
Nordgren Ann,
Mäkitie Outi
Publication year - 2014
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.36502
Subject(s) - short stature , scoliosis , phenotype , medicine , pediatrics , mutation , genetics , biology , gene , surgery
Autosomal dominant brachyolmia (Type 3, OMIM #113500) belongs to a group of skeletal dysplasias caused by mutations in the transient receptor potential cation channel, subfamily V, member 4 ( TRPV4 ) gene, encoding a Ca ++ ‐permeable, non‐selective cation channel. The disorder is characterized by disproportionate short stature with short trunk, scoliosis and platyspondyly. The phenotypic variability and long‐term natural course remain inadequately characterized. The purpose of this study was to describe a large Swedish family with brachyolmia type 3 due to a heterozygous TRPV4 mutation c.1847G>A (p.R616Q) in 11 individuals. The mutation has previously been detected in another family with autosomal dominant brachyolmia [Rock et al., 2008]. Review of hospital records and patient assessments indicated that clinical symptoms of brachyolmia became evident by school age with chronic pain in the spine and hips; radiographic changes were evident earlier. Growth was not affected during early childhood but deteriorated with age in some patients due to increasing spinal involvement. Affected individuals had a wide range of subjective symptoms with chronic pain in the extremities and the spine, and paresthesias. Our findings indicate that autosomal dominant brachyolmia may be associated with significant long‐term morbidity, as seen in this family. © 2014 Wiley Periodicals, Inc.