Hereditary Sensory and Autonomic Neuropathy Type V (HSAN V)

At a glance

Group of genetically inherited disorders that share the primary feature of progressive, generally severe, lower extremity spasticity. Type V is defined as medical condition. It is associated with congenital insensitivity to pain with partial anhidrosis. However, it is also possible to observe this disease in presence of anhidrosis. The signs and symptoms of HSAN5 appear early, usually at birth or during infancy. Characteristically, individuals loose the perception of deep pain, absence of pain with bone injuries, ligaments, or muscles. The clinical presentation of these patients is repeated severe injuries that go unnoticed. Repeated trauma is eventually associated with destruction of the articulations, a condition called Charcot joints. It is differentiated from HSAN4 by the absence of myelinated sensory fibers on large conducting nervous structures.

Synonyms

Diplegia Spinalis Progressive; Familial Spastic Paraplegia (or Paraparesis) (FSP); French Settlement Disease (FSD); Hereditary Charcot Disease; Hereditary Progressive Spastic Paraplegia; Hereditary Sensory Neuropathies Type V; Spastic Paraplegia (SPG); Spastic Spinal Paralysis (SSP); Strümpell-Lorrain Syndrome; Strümpell Disease.

History

First described by Ernst Adolf Gustav Gottfried von Strümpell, a German neurologist, in 1880. Subclassified into pure (or uncomplicated) and complicated forms based on the presence of additional neurologic or nonneurologic features.

Incidence

Pure hereditary spastic paraplegia is the most common form of hereditary spastic paraplegia, with a prevalence of 9.6:100,000 in the general population of Spain.

Genetic inheritance

Autosomal dominant inheritance accounts for 70 to 80% of cases, with autosomal recessive inheritance responsible for most of the remainder. X-linked recessive inheritance is very rare. Three autosomal dominant genes causing pure hereditary spastic paraplegia have been mapped on chromosomes 2p, 14q, and 15q. A new locus for hereditary spastic paraplegia (HSP) gene has been mapped to chromosome 13q12.3 (encoding spartin); it is responsible for a recessive form of complicated HSP (Troyer Syndrome) that is found mainly in patients of Old Order Amish descent.

Pathophysiology

Axonal degeneration involving the terminal ends of the longest fibers of the corticospinal tracts and dorsal columns. The spinocerebellar tracts are less affected. The cell bodies of the involved fibers are normal.

Diagnosis

Magnetic resonance imaging (MRI) scans may show spinal cord atrophy, especially in the cervical region. Sensory polyneuropathy is observed on electrophysiologic studies. Normal motor nerve conduction velocities on electromyography (EMG) are present. Severe loss of large diameter sensory fibers have been shown on sural nerve biopsies accompanied by relative preservation of small myelinated and nonmyelinated fibers. Prenatal testing is possible in families with SPG2 with an identified PLP gene (chromosomal locus Xq28) mutation only.

Clinical aspects

Progressive spastic paraplegia manifests as insidious onset of an abnormal gait. The age of onset ranges from childhood ...