title: Long-Term Observations in an Affected Family with Neurogenic Scapuloperoneal Syndrome Caused by Mutation R269C in the TRPV4 Gene.
abstract: Mutations in the TRPV4 gene, encoding a polymodal Ca(2+) permeable channel, are causative for several human diseases, affecting the skeletal and the peripheral nervous system with highly variable phenotypes. We report on a family with two affected individuals. The father clinically suffered from a classical scapuloperoneal syndrome, while the son presented with a severe neonatal onset with congenital respiratory distress, feeding problems and arthrogryposis multiplex. Multi-Gene Panel sequencing by next generation sequencing revealed the heterozygous mutation c.805C>T (p.R269C) in the TRPV4 gene. Long-term observation over two decades showed no relevant disease progression in the father and, after a dramatic neonatal period, a significant improvement in the son who became ambulant with orthoses at the age of 5 years, suggesting a reasonably good prognosis even in cases with severe neonatal onset. Long-term findings in muscle ultrasound correlated with the clinical course, showing stable or even slightly improved findings. Neurography revealed a late-onset sensory neuropathy in the father, which was so far not described in TRPV4 neuropathies.
authors.affiliation: Department of Pediatric Neurology and Developmental Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Vill
authors.affiliation: Genetikum Center for Human Genetics, Neu-Ulm, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Kuhn
authors.affiliation: Genetikum Center for Human Genetics, Neu-Ulm, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Gläser
authors.affiliation: Friedrich-Baur-Institute, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Maggie C
authors.initials: MC
authors.lastname: Walter
authors.affiliation: Department of Pediatric Neurology and Developmental Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Müller-Felber
mesh_terms: D000293:Adolescent; D001176:Arthrogryposis / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D020271:Heredodegenerative Disorders, Nervous System / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009134:Muscular Atrophy, Spinal / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D050916:TRPV Cation Channels / Q000235:genetics*
chemical_list: D050916:TRPV Cation Channels; C416986:TRPV4 protein, human