Monogenic hearing loss
Gene: TRPV4
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
#113500:Brachyolmia type 3[Normal birth lengthShort stature, disproportionate (short trunk), identifiable in childhood; Hyperopia; Short neck; Barrel-shaped chest; GibbusKyphosisScoliosisMarked platyspondyly; Short femoral neckIrregular proximal femoral metaphyses; Clinodactyly; Normal intelligenceSpinal cord compression; Caused by mutation in the transient receptor potential cation channel, subfamily V, member 4 gene (TRPV4,).]; #156530:Metatropic dysplasia[Dwarfism, short limbed, recognizable at birth; Respiratory failure; Exuberant cartilage formation in the trachea and bronchi; Narrow thorax; Short ribs with cupped ends; Arthrogryoposis multiplex (in some patients)Joint contractures (in some patients); Relatively short spineSevere scoliosisSevere kyphosisLong coccyxAnisospondylyCoccygeal tailPlatyspondylyVertebral bodies broader than interpedicular distance; Halberd-shaped pelvisHyperplastic femoral trochantersSupra-acetabular notches; Flared femurs and humeriDumbbell-shaped metaphysesEpiphyseal dysplasiaProminent jointsA thin seal of bone at the chondroosseous junctionAbsent primary metaphyseal spongiosaAbnormal metaphyseal vascular invasionArrest of endochondral ring structures with persistence of circumferential growth; BrachydactylyDelayed carpal age; Fetal akinesia (in some patients)Peripheral axonal neuropathy (in some patients); Decreased fetal movements (in some patients); Caused by mutation in the transient receptor potential cation channel, subfamily V, member 4 gene (TRPV4,)]; #168400:Parastremmatic dwarfism[Dwarfism identifiable during late infancy; Average adult height: 90 to 110 cm; Normocephaly; Kyphosis; Scoliosis; Short neck; Severe genu valgum; Bowing of long bones; Legs twisted along the long axis; Joint contractures; Normal intelligence; Coarse bone trabeculations with areas of irregular, dense stippling and streaking; Lace-like border of the iliac crests]; #181405:Scapuloperoneal spinal muscular atrophy[Facial weakness; Abducens palsy; Weak neck flexionTorticollis; Respiratory insufficiency in infancyRespiratory stridor in infancy; Laryngeal palsy; Rounded shoulders due to muscle atrophy; Laterally placed scapulaeScapular winging; Diaphragmatic weakness; HyperlordosisScoliosisKyphosis; Hip dysplasia; Asymmetric limb length (less common); Small handsClinodactyly; Club feetMetatarsus varus; Amyotrophy, neurogenicScapular muscle weaknessScapular muscle atrophyAbsence of some scapular muscles (less common)Peroneal muscle weaknessPeroneal muscle atrophyMuscle weakness, distal, upper and lower limbsMuscle atrophy, distal, upper and lower limbsGowers signMuscle biopsy shows grouped atrophyFatty replacementIncreased endomysial fibrosisMarked variability of fiber sizeMany fibers with internal nucleiFiber splittingAtrophy of type 1 and type 2 fibers; Delayed motor developmentWide-based gait; Peripheral motor neuropathyHyporeflexiaAreflexiaDecreased distal sensation (less common); Hoarse voice due to laryngeal palsy]; #184095:SED, Maroteaux type[Spondyloepiphyseal dysplasia; Platyspondyly; Normal intelligence; No corneal clouding; Short and stubby hands and feet; Genu valgum; Champagne-glass configuration of pelvic inlet; No mucopolysacchariduria]; #184252:Spondylometaphyseal dysplasia, Kozlowski type[Short-trunked dwarfismAdult height 130-150 cm; Normal facies; Short neck; Pectus carinatum; Delayed skeletal maturation; Sphenoid hypoplasia; Odontoid hypoplasiaPlatyspondylyScoliosisKyphoscoliosisOpen staircase vertebral bodiesMedially places pediclesVertebral bodies broader than interpedicular distance; Square, short iliac wingsFlaring of iliac wingsFlat, irregular acetabulaCoxa varaSupra-acetabular notches (in some patients); Irregular, rachitic-like metaphysesMildly curved limbs (varus)Metaphyseal irregularityMetaphyseal flaringProminent joints (in some patients); Hypoplastic carpal bonesSevere carpal ossification delayShort, stubby hands; Short, stubby feet]; #600175:Spinal muscular atrophy, distal, congenital nonprogressive[Arthrogryposis; LordosisScoliosisKyphosis; Hip contractures; Elbow contracturesKnee contractures; Club feetPes equinovarusPes planus; Muscle weakness, distal, restricted to the lower limbsMuscle atrophy, distalMuscle weakness, proximal, pelvic girdle (in severe cases)Trunk muscle weaknessMuscle biopsy shows groups of small angulated fibers consistent with denervationType II fiber predominanceMRI of the thighs shows fatty atrophy with preservation of the biceps femoris in the lateral compartmentMRI of the calves shows fatty atrophy with preservation of the medial gastrocnemius in the posteromedial compartment; AreflexiaHyporeflexia; Decreased fetal movement]; #606071:Hereditary motor and sensory neuropathy, type IIc[Short stature (in some patients); Hearing loss, sensorineural; Abducens nerve palsyOculomotor nerve palsy; Respiratory failure due to intercostal muscle and diaphragm involvementObstructive sleep apneaStridor; Vocal cord paresis; Urinary urgencyUrinary incontinence; Scoliosis; ' Sloping' shoulders due to muscle atrophyShoulder girdle muscle atrophyNeurogenic atrophy seen on muscle biopsy; Distal limb muscle weakness due to peripheral neuropathyDistal limb muscle atrophy due to peripheral neuropathyBoth upper and lower limb involvementWasting of hand muscles often occurs earlyImpaired manual dexterityProximal limb muscles may be involved in severe casesFoot dropIntercostal muscle involvementDiaphragm involvementVocal cord paresisAreflexiaHyporeflexiaDistal sensory impairmentDecreased or absent distal sensory nerve action potential (SNAP)Normal motor nerve conduction velocity (NCV) (greater than 38 m/s)Decreased compound muscle action potentials (CMAP); Hoarse voice due to vocal cord paresis]; #606835:Digital arthropathy-brachydactyly, familial[Normal bone age; Radially deviated phalangesProgressive brachydactyly of middle and distal phalangesProgressive arthropathy of the interphalangeal and metacarpophalangeal joints; Progressive brachydactyly of middle and distal phalangesProgressive arthropathy of the interphalangeal and metatarsophalangeal joints]; #613508:[Sodium serum level QTL 1][<omim version=1.0><clinicalSynopsisList>]
Publications
TRPV4 was added to Congenital hearing impairment (Profound/Severe)panel. Sources: Expert