From OMIMThe hereditary spastic paraplegias are a group of clinically and genetically diverse disorders characterized by progressive, usually severe, lower extremity spasticity; see reviews of Fink et al. (1996) and Fink (1997). Zhao et al. (2001) noted that hereditary spastic paraplegia in the families of the SPG3A variety is characterized by early onset (before age 10 and usually before age 5 years).
SPG is classified according to both the mode of inheritance (autosomal dominant, autosomal recessive (see 270800), and X-linked (see 303350)) and whether progressive spasticity occurs in isolation ('uncomplicated SPG') or with other neurologic abnormalities ('complicated SPG'), including optic neuropathy, retinopathy, extrapyramidal disturbance, dementia, ataxia, ichthyosis, mental retardation, and deafness. The major neuropathologic feature of autosomal dominant, uncomplicated SPG is axonal degeneration that is maximal in the terminal portions of the longest descending and ascending tracts (crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis, respectively). Spinocerebellar fibers are involved to a lesser extent. Since the description of 'pure' hereditary spastic paraparesis of late onset by Strumpell (1904), many 'complicated' forms of the disorder have been reported and the question as to whether a 'pure' form exists has been raised off and on. Probably in large part because of their exceptional length, the pyramidal tracts are unusually vulnerable to both acquired and genetic derangement. Although a majority of reported families have displayed recessive inheritance, 10 to 30% of families have a dominant pattern and in fact recessive inheritance of a 'pure' spastic paraplegia may be rare.
Genetic Heterogeneity of Autosomal Dominant Spastic Paraplegia
In addition to SPG3A, other forms of autosomal dominant spastic paraplegia for which the molecular basis is known include SPG4 (182601), caused by mutation in the SPAST gene (604277) on 2p22; SPG6 (600363), caused by mutation in the NIPA1 gene (608145) on 15q11; SPG8 (603563), caused by mutation in the WASHC5 gene (610657) on 8q24; SPG9A (601162), caused by mutation in the ALDH18A1 gene (138250) on 10q24; SPG10 (604187), caused by mutation in the KIF5A gene (602821) on 12q13; SPG12 (604805), caused by mutation in the RTN2 gene (603183) on 19q13; SPG13 (605280), caused by mutation in the SSPD1 gene (118190) on 2q33; SPG17 (270685), caused by mutation in the BSCL2 gene (606158) on 11q12; SPG18A (620512), caused by mutation in the ERLIN2 gene (611605) on 8p11; SPG30 (610357), caused by mutation in the KIF1A gene (601255) on 2q37; SPG31 (610250), caused by mutation in the REEP1 gene (609139) on 2p11; SPG33 (610244), caused by mutation in the ZFYVE27 gene (610243) on 10q24; SPG42 (612539), caused by mutation in the SLC33A1 gene (603690) on 3q25; SPG72 (615625), caused by mutation in the REEP2 gene (609347) on 5q31; SPG73 (616282), caused by mutation in the CPT1C gene (608846) on 19q13; SPG79A (620221), caused by mutation in the UCHL1 gene (191342) on chromosome 4p13; SPG80 (618418), caused by mutation in the UBAP1 gene (609787) on 9p13; SPG88 (620106), caused by mutation in the KPNA3 gene (601892) on 13q14; SPG90A (620416), caused by mutation in the SPTSSA gene (613540) on 14q13; and SPG91 (620538), caused by mutation in the SPTAN1 gene (182810) on 9q34.
Autosomal dominant spastic paraplegia has been mapped to chromosomes 9q (SPG19; 607152), 1p31-p21 (SPG29; 609727), 12q23-q24 (SPG36; 613096), 8p21.1-q13.3 (SPG37; 611945), 4p16-p15 (SPG38; 612335), and 11p14.1-p11.2 (SPG41; 613364).
http://www.omim.org/entry/182600 From MedlinePlus GeneticsIn addition to spasticity and weakness, which typically affect both legs equally, people with spastic paraplegia type 3A can also experience progressive muscle wasting (amyotrophy) in the lower limbs, reduced bladder control, an abnormal curvature of the spine (scoliosis), loss of sensation in the feet (peripheral neuropathy), or high arches of the feet (pes cavus). The signs and symptoms of spastic paraplegia type 3A usually appear before the age of 10; the average age of onset is 4 years. In some affected individuals the condition slowly worsens over time, sometimes leading to a need for walking support.
Spastic paraplegia type 3A is one of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by muscle stiffness (spasticity) and weakness in the lower limbs (paraplegia). Hereditary spastic paraplegias are often divided into two types: pure and complex. The pure types involve only the lower limbs, while the complex types also involve other areas of the body; additional features can include changes in vision, changes in intellectual functioning, difficulty walking, and disturbances in nerve function (neuropathy). Spastic paraplegia type 3A is usually a pure hereditary spastic paraplegia, although a few complex cases have been reported.
https://medlineplus.gov/genetics/condition/spastic-paraplegia-type-3a