IDC-10 Code = G12.8
Genomic coordinate (human 12:109,783,087 TRPV4).
Cytoband (human 12q24.11 TRPV4).
Intraband %= TRPV4
OMIM’ genes @ 12q24.11 = 34 genes.
ClinVar = 1,336 TRPV4 variants reported.
Hyperbolic Umbilic Chromosome-12 is 1,200 genes.
白灰₂黑₂灰縊_縊黑灰₅黑₂灰₆
Chromosome-12 Cytobands: WG2B2GC_CBG5B2G6
Here I present: “Scapuloperoneal Spinal Muscular Atrophy”, Victor McKusick, Mendelian Inheritance in Man’, 1966. (TRPV4)
Scapuloperoneal spinal muscular atrophy (SPSMA) is an autosomal dominant genetic disorder caused by heterozygous, gain-of-function missense mutations in the TRPV4 gene on chromosome 12q24. This gene encodes the transient receptor potential vanilloid 4 protein, a calcium-permeable, non-selective cation channel. Mutations cause increased calcium influx, leading to intracellular calcium overload and subsequent neurotoxicity.
Clinical Presentation
SPSMA primarily impacts motor neurons, resulting in a non-length-dependent neuropathy characterized by distinct muscle and skeletal patterns:
Muscle Atrophy: Severe, progressive wasting and weakness in the shoulder girdle (scapular winging) and lower legs (peroneal distribution).
- Laryngeal Dysfunction: Vocal fold paresis often causes a hoarse voice, inspiratory stridor, or respiratory difficulties.
- Skeletal Deformities: Variable presentations include scoliosis, congenital hip dysplasia, clubfoot, and short stature.
- Congenital Features: Arthrogryposis (joint contractures) or the congenital absence of specific muscles can be present at birth.
Allelic Disorders & Overlap
Because mutations occur in the same TRPV4 gene, SPSMA belongs to a broader spectrum of “TRPV4-pathies”. It shares significant clinical and genetic overlap with:
- Charcot-Marie-Tooth Disease Type 2C (CMT2C): An axonal neuropathy that can present within the same families, sometimes showing overlap features in a single individual.
- Congenital Distal Spinal Muscular Atrophy (CDSMA): A predominantly motor disorder affecting the distal extremities.
- Skeletal Dysplasias: Conditions like metatropic dysplasia or Kozlowski-type spondylometaphyseal dysplasia.
The clinical severity can vary significantly between generations, occasionally showing more aggressive onset in offspring.
