Molecular genetics of HSP

Genotype

Gene / Gene locus

Phenotype

Autosomal dominant HSP

SPG3

Atlastin / 14q11-q21

„pure“ HSP

SPG4

Spastin / 2p22-p21

Mostly „pure“ HSP, rare: Dementia, cerebellar ataxia, thin corpus callosum

SPG6

NIPA1 / 15q11.1

„pure“ HSP

SPG8

8q23-q24

„pure“ HSP

SPG9

10q23.3-q24.1

„pure“ HSP

SPG10

KIF5A / 12q13

HSP with cataract, peripheral neuropathy, skeletal deformities, gastroesophageal reflux

SPG12

19q13

„pure“ HSP

SPG13

HSP60 (Chaperonin) / 2q33.1

„pure“ HSP

SPG17

Seipin (BSCL2) / 11q12-q14

Silver-Syndrome: HSP with wasting of intrinsic hand muscles

Allelic with distal spinal muscular atrophy type V and congenital generalised lipodystrophy type 1 / Berardinelli-Seip Syndrome

SPG19

9q33-q34

HSP with peripheral neuropathy

SPG29

1p31.1-p21.1

HSP with deafness and vomiting due to hiatic hernia

Autosomal rezessive HSP

SPG5

8q12-q13

„pure“ HSP

SPG7

Paraplegin / 16q24

HSP with optic atrophy, sensory deficits, skeletal deformities

SPG11

15q13-q15

HSP with cognitive deficits and thin corpus callosum

SPG14

3q27-q28

HSP with cognitive deficits and peripheral neuropathy

SPG15

14q22-q24

HSP with cognitive deficits, retina degeneration und amyotrophy

SPG20

13q12.3

Troyer syndrome: HSP with cerebellar ataxia and wasting of intrinsic hand muscles

SPG21

Maspardin (ACP33) / 15q21-q22

MAST syndrome: HSP with cognitive deficits and thin corpus callosum; cerebellar ataxia and extrapyramidal symptoms

SPG23

1q24-q32

HSP with cognitive deficits and abnormality pigmentation of skin and hair

SPG24

13q14

„pure“ HSP

SPG25

6q23-q24.1

HSP with disc herniation

SPG26

12p11.1-q14

HSP with distal muscle wasting

SPG27

10q22.1-q24.1

„pure“ HSP

SPG28

14q21-22

„pure“ HSP

SPG30

2p

HSP with peripheral neuropathy and saccadic smooth pursuit

SPG32

14q

„pure“ HSP

X-linked HSP

SPG1

L1CAM / Xq28

CRASH syndrome: Corpus callosum hypoplasia, retardation, adducted thumbs, spasticity and hydrocephalus. Variants:

HSAS: Hydrocephalus due to congenital stenosis of aquaedutcus Sylvius

MASA syndrome: Mental retardation, aphasia, shuffling gait, adducted thumbs

ACC: Agenesis corpus callosum

SPG2

PLP1 / Xq22

„pure“ HSP or HSP with mental retardation, optic atrophy, cerebellar syndrome.

Allelic with Pelizaeus-Merzbacher disease

SPG16

Xq11.2

HSP with kognitive defizits, tetraparesis, maxiallary hypolpasia

SPG22

X121

Alan-Herndorn-Dudley syndrome: HSP with cognitive deficits, ataxia, athetosis, muscular hypoplasia, facial dysmorphia