Referenced in: none

Automatically associated channels: TRP , TRPV , TRPV4

Title: Autosomal dominant brachyolmia in a large Swedish family: phenotypic spectrum and natural course.

Authors: Giedre Grigelioniene, Stefan Geiberger, Eva Horemuzova, Eva Moström, Nina Jäntti, Lo Neumeyer, Eva Åström, Magnus Nordenskjöld, Ann Nordgren, Outi Mäkitie

Journal, date & volume: Am. J. Med. Genet. A, 2014 Jul , 164A, 1635-41

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24677493

Abstract
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.