Scapuloperoneal spinal muscular atrophy (ORPHA:431255)
A rare, genetic motor neuron disease characterized by predominantly motor axonal peripheral neuropathy manifesting with progressive scapuloperoneal muscular atrophy and weakness, laryngeal palsy, congenital absence of muscles, and, in some, skeletal abnormalities.
Epidemiology
The precise prevalence of Scapuloperoneal spinal muscular atrophy (SPSMA) is not available. To date, more than 30 affected individuals have been described worldwide. Males are more severely affected than females.
Clinical description
Onset is usually congenital or occurs in infancy or early childhood. Clinical hallmarks of SPSMA are muscular atrophy of the shoulders, peroneal and small hand muscles resulting in distal weakness, predominantly of the lower limbs, and pectoral muscle wasting and weakness. Patients present difficulty walking on heels, winged scapulae, and diminished or absent deep tendon reflexes. Other common features reported include vocal cord paralysis, scoliosis, and/or arthrogryposis. Skeletal abnormalities have been described in some patients, including congenital hip dysplasia, short limbs/limb length discrepancy, bilateral congenital clubfoot, metatarsal dysplasia, spondylometaphyseal dysplasia, platyspondyly, metatropic dysplasia, and/or mild short stature. Mildly diminished vibration sense may also be associated. The disease has slow clinical progression and variable pattern of expression, ranging from severe neonatal onset to mild symptoms referred only in adulthood.
Etiology
The causative gene of SPSMA is TRPV4 (12q23-q24.1), which encodes for a calcium, nonselective cation channel thought to be involved in the regulation of systemic osmotic pressure and mechanosensitivity. De novo mutations have also been reported in the literature.
Diagnostic methods
Diagnosis is based on clinical manifestations, family history and biopsy findings which reveal severe muscle fiber-type grouping and atrophy, extensive fatty replacement, increased endomysial fibrosis, marked variability of fiber size, fiber splitting, and many fibers with multiple internal nuclei. Pathological changes are particularly severe in the gastrocnemius muscle. Atrophy of both type 1 and type 2 fibers can be observed with ATPase staining. Electroradiography shows reduced compound motor action potentials (cMAPS) but normal sensory action potentials and nerve conduction velocity. Brain and spinal cord sections reveal normal numbers of motor neurons in the motor complex and spinal cord. Genetic testing which reveals a pathogenic mutation confirms diagnosis.
Differential diagnosis
The differential diagnosis includes Charcot-Marie-Tooth disease type 2C, congenital distal spinal muscular atrophy, neurogenic scapuloperoneal syndrome Kaeser type, and facioscapulohumeral dystrophy.
Antenatal diagnosis
Prenatal diagnosis is possible if a pathogenic variant has been previously identified in the family.
Genetic counseling
SPSMA has an autosomal dominant pattern of inheritance. Genetic counseling can inform parents of the 50% risk of transmitting the mutation responsible for the disease to their children. Early diagnosis is crucial to prevent the more severe congenital form, as disease tends to be more progressive and severe in succeeding generations.
Management and treatment
There is no effective treatment to date.
Prognosis
The prognosis is not so poor, even if the problems of ambulation predispose to falls, to the development of arthrosic problems, which together with the dysmorphic aspects and the distal weakness contribute to get worse the motor problems. Generally the respiratory muscles are not involved.

                            Last update: 
                            May 2019


                            - Expert reviewer(s): 
                            Pr Carmelo RODOLICO