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Hereditary spastic paraplegias

53 articles

Autosomal recessive spastic paraplegia type 48

Autosomal recessive spastic paraplegia type 48 (SPG48, OMIM 613647) is a rare hereditary spastic paraplegia caused by AP5Z1 mutations at 7p22.1, with adult-onset spastic paraplegia, urinary incontinence, and complex features including parkinsonism and thin corpus callosum.

Autosomal recessive spastic paraplegia type 54

Autosomal recessive spastic paraplegia type 54 (SPG54, hereditary spastic paraplegia 54) is a rare complex HSP caused by biallelic DDHD2 mutations (8p11.23), with early-onset spastic paraplegia, intellectual disability, thin corpus callosum, and a thalamic lipid peak on MRS.

Autosomal recessive spastic paraplegia type 55

SPG55, autosomal recessive spastic paraplegia type 55, C12ORF65-related HSP: rare childhood-onset complex hereditary spastic paraplegia with optic atrophy, ophthalmoplegia, and sensorimotor neuropathy, caused by C12ORF65 mutations at 12q24.31 (OMIM 615035).

Autosomal recessive spastic paraplegia type 57

SPG57 (autosomal recessive spastic paraplegia type 57, ORPHA431329, OMIM 615658) is an extremely rare complex hereditary spastic paraplegia caused by TFG gene mutations at 3q12.2, with infancy-onset leg spasticity, optic atrophy, and distal neuropathy.

Autosomal recessive spastic paraplegia type 5A

SPG5A (SPG5, OMIM 270800) is a rare autosomal recessive hereditary spastic paraplegia caused by CYP7B1 mutations, causing oxysterol accumulation, progressive leg spasticity, and elevated plasma 27-hydroxycholesterol as a diagnostic biomarker.

Autosomal recessive spastic paraplegia type 61

SPG61 (autosomal recessive spastic paraplegia type 61, ARL6IP1 complex spastic paraplegia) is a rare infantile-onset complicated hereditary spastic paraplegia caused by biallelic ARL6IP1 mutations at 16p12.3, featuring scissors gait, polyneuropathy, and digit loss; OMIM 615685.

Autosomal recessive spastic paraplegia type 64

Autosomal recessive spastic paraplegia type 64 (SPG64, ENTPD1-related neurodevelopmental disorder) is an ultra-rare complex hereditary spastic paraplegia caused by biallelic ENTPD1 mutations at 10q24.1, with childhood-onset spastic paraplegia and intellectual disability.

Autosomal recessive spastic paraplegia type 76

SPG76 (OMIM 616907) is a rare autosomal recessive hereditary spastic paraplegia caused by CAPN1 mutations at 11q13.1, with adult-onset lower limb spasticity, gait disturbance, ataxia, dysarthria, and pes cavus.

Autosomal recessive spastic paraplegia type 78

Autosomal recessive spastic paraplegia type 78 (SPG78, OMIM 617225) is a rare complex hereditary spastic paraplegia caused by biallelic ATP13A2 mutations at 1p36.13, with adult-onset lower-limb spasticity, axonal neuropathy, cerebellar ataxia, and cognitive impairment, overlapping Kufor-Rakeb syndrome.

Autosomal spastic paraplegia type 18

Autosomal spastic paraplegia type 18 (SPG18), also hereditary spastic paraplegia 18, is a rare complex HSP caused by ERLIN2 mutations, with childhood-onset spastic paraplegia, intellectual disability, joint contractures, and possible ALS conversion.

Autosomal spastic paraplegia type 30

Autosomal spastic paraplegia type 30 (SPG30, OMIM 610357) is a rare hereditary spastic paraplegia caused by KIF1A mutations at 2q37.3, inherited dominantly or recessively, with pure or complicated spastic paraplegia beginning in the first or second decade.

Autosomal spastic paraplegia type 58

Autosomal spastic paraplegia type 58 (SPG58, SPAX2, autosomal spastic ataxia type 2) is a rare hereditary spastic paraplegia caused by KIF1C mutations, combining lower limb spasticity with cerebellar ataxia, with mild dominant and severe recessive phenotypes.

Autosomal spastic paraplegia type 72

Autosomal spastic paraplegia type 72 (SPG72, SPG72A, OMIM 615625) is a rare pure hereditary spastic paraplegia caused by REEP2 mutations, with childhood onset spastic gait, hyperreflexia, and both dominant and recessive inheritance.

Infantile-onset ascending hereditary spastic paralysis

Infantile-onset ascending hereditary spastic paralysis (IAHSP), also called infantile-onset ascending hereditary spastic paraplegia, is a rare autosomal recessive ALS2-gene motor neuron disorder: leg spasticity begins before age 2 and ascends to arms, speech, and swallowing, sparing intelligence.

Kjellin syndrome

Kjellin syndrome, also called SPG15 or spastic paraplegia-retinal degeneration syndrome, is a rare autosomal recessive HSP with retinal degeneration, thin corpus callosum, intellectual disability, and amyotrophy; more often caused by SPG11 than ZFYVE26 mutations.

Laurence-Moon syndrome

Laurence-Moon syndrome (LMS, OMIM 245800, ORPHA 2377) is a very rare autosomal recessive PNPLA6-related disorder with progressive spastic paraplegia, chorioretinal dystrophy, and hypogonadism, distinct from Bardet-Biedl syndrome.

NESCAV syndrome

NESCAV syndrome, formerly autosomal dominant intellectual disability type 9, is a rare neurodegenerative KIF1A disorder beginning in infancy, causing developmental delay, absent speech, and progressive lower-limb spasticity.

Severe intellectual disability and progressive spastic paraplegia

Severe intellectual disability and progressive spastic paraplegia, now called AP-4 deficiency syndrome, is a rare autosomal recessive hereditary spastic paraplegia causing developmental delay, severe intellectual disability, and progressive spasticity.

Spastic paraplegia type 7

Spastic paraplegia type 7 (SPG7) is a rare autosomal recessive hereditary spastic paraplegia caused by SPG7 gene variants encoding mitochondrial paraplegin, with adult-onset leg spasticity, ataxia, and optic atrophy.

Spastic paraplegia-intellectual disability-nystagmus-obesity syndrome

SINO syndrome (spastic paraplegia-intellectual disability-nystagmus-obesity syndrome, ORPHA:521390, OMIM 617296) is a rare autosomal dominant KIDINS220-related neurodevelopmental disorder with congenital spastic paraplegia, intellectual disability, nystagmus, and obesity.

Spastic paraplegia-optic atrophy-neuropathy syndrome

SPOAN syndrome (spastic paraplegia-optic atrophy-neuropathy syndrome, OMIM 609541) is an autosomal recessive hereditary spastic paraplegia caused by a 216-bp non-coding deletion upregulating KLC2 on 11q13, concentrated in northeastern Brazil, with congenital optic atrophy, infancy-onset spastic paraplegia, and axonal neuropathy.

X-linked hereditary spastic paraplegia

X-linked hereditary spastic paraplegia (SPG, ICD-11 8B44.02): HSP form inherited on the X chromosome, mainly PLP1 (Xq22) and GJC2/connexin 47 mutations, causing corticospinal tract axon degeneration and lower limb spasticity.

X-linked spastic paraplegia type 16

X-linked spastic paraplegia type 16 (SPG16, OMIM 300266) is a rare X-linked recessive hereditary spastic paraplegia mapped to Xq11.2 with the gene unknown, causing infantile-onset spasticity, inability to walk, quadriplegia, motor aphasia, and intellectual disability in males only.