Disease (OMIM) | Inheritance | Gene | Clinical description |
(a) Extrapyramidal disease and neuropathy syndromes | |||
Leukoencephalopathy with dystonia and motor neuropathy (613724) | AR | SCP2 | Dystonia, hyposmia, azoospermia, motor predominant axonal neuropathy, bilateral thalamic T2 high signal on MRI |
MTDPS4B (613662) | AR | POLG | SANDO: Sensory Axonal Neuropathy, Dysarthria, Ophthalmoplegia, also parkinsonism and deafness. Also caused by recessive C10orf2 mutations |
Chorea acanthocytosis (200150) | AR | VPS13A | Onset third to fifth decade, red cell acanthocytosis and progressive neurodegeneration, seizures, dysarthria, chorea, orofacial dyskinesia, psychiatric disturbance, axonal sensory-motor neuropathy, raised CK |
McLeod syndrome (300842) | XL | XK | Onset 25–60, acanthocytes and Huntington-like syndrome, also epilepsy, cardiomyopathy, axonal motor neuropathy. |
CMT2P (614436) | AD/AR | LRSAM1 | Onset third to eighth decade. Late-onset parkinsonism described |
DSMA 5 (614881) | AR | HSJ1 | Onset second decade, motor predominant axonal neuropathy, rarely late-onset parkinsonism |
Mitochondrial disease | m1095T>C | MTRNR1 (561000) | Parkinsonism, deafness and sensory-motor axonal neuropathy |
SPG10 (604187) | AD | KIF5A | See table 1b |
MTDPS5 (612073) | AR | SUCLA2 | See table 1c |
(b) Ophthalmological and neuropathy syndromes | |||
Optic atrophy and neuropathy syndromes | |||
Syndromic optic atrophy (125250) | AD | OPA1 | Optic neuropathy, PEO, deafness, myelopathy, sensory-motor axonal neuropathy |
Costeff syndrome or OPA3-related 3-methylglutaconic aciduria (258501) Optic atrophy and cataracts (165300) | AR/AD | OPA3 | Infantile optic atrophy, additionally, extra pyramidal disorder (chorea), ataxia, cognitive defects, axonal sensory neuropathy, autonomic neuropathy, pseudo-obstruction |
Leber optic atrophy (53500) | Mitochondrial | MT-ND1, ND4, ND6 | Optic atrophy, rarely neuropathy, spasticity, ataxia and extrapyramidal signs |
HMSN6B (616505) | AR | SLC25A46 | Optic atrophy and progressive visual loss in the first decade, then spasticity, cerebellar ataxia, sensory-motor axonal neuropathy |
CMTX5 (311070) | X-linked | PRPS1 | Hearing loss, optic atrophy, sensory-motor axonal neuropathy |
BVVLS2 (614707) | AR | SLC52A2 | Facial and bulbar weakness, sensory ataxia, sensory-motor axonal neuropathy, optic atrophy, sensory neuronal hearing loss |
SPOAN (609541) | AR | KLC2 | See table 1b |
SPG7 (607259) | AR | PGN | See table 1b |
SPG43 (615043) | AR | C19orf12 | See table 1b |
SPG55 (615035) | AR | C12ORF65 | See table 1b |
SPG57 (615658) | AR | TFG | See table 1b |
Metachromatic leukodystrophy (250100) | AR | ARSA | See table 1c |
Krabbe disease (245200) | AR | GALC | See table 1c |
EMPF2 (617086) | AR | MFF | Leigh-like syndrome, see table 1c |
Cockayne syndrome (216400/133540) | AR | ERCC6/ERCC8 | See table 1c |
Hexosaminidase A deficiency (272800) | AR | HEXA | See table 1c |
Sandhoff disease (268800) | AR | HEXB | See table 1c |
HAYOS (617183) | AD | ATAD3A | See table 1c |
Retinitis pigmentosa and neuropathy syndromes | |||
Methylmalonic aciduria and homocystinuria type Cb1c (MMACHC) (277400) | AR | MMACHC | Onset infancy to adulthood; thrombotic thrombocytopenia with encephalopathy, myelopathy, renal and pulmonary complications (can be life threatening), retinitis pigmentosa, axonal motor neuropathy; treat with high-dose B12 |
Kearns-Sayre syndrome (530000) | Mitochondrial | Ophthalmoplegia, retinitis pigmentosa, heart block, ptosis | |
Posterior column ataxia and retinitis pigmentosa (PCARP/6 09 033) | AR | FLVCR1 | Retinitis pigmentosa, sensory ganglionopathy and abnormal posterior columns on MRI |
NARP (551500) | Mitochondrial | MTATP6 | See table 1a |
Refsum’s disease (266500) | AR | PHYH | See table 1a |
PHARC syndrome (612674) | AR | ABHD12 | See table 1a |
AMACRD (614307) | AR | AMACR | See table 1b |
SPG15 (270700) | AR | ZFYVE26 | See table 1b |
Cockayne syndrome (216400/133540) | AR | ERCC6/ERCC8 | See table 1c |
PBD9B (Refsum variant) (614879) | AR | PEX7 | See table 1c |
Congenital disorder of glycosylation type 1A (212065) | AR | PMM2 | See table 1c |
Cataracts and neuropathy syndromes | |||
Congenital cataracts, facial dysmorphism and neuropathy (604168) | AR | CTDP1 | Rudari Gypsies, congenital cataracts and microcornea, facial dysmorphism, mild cognitive impairment, neuropathy with SNCV |
CMTD1B or CMT2M (606482) | AR | DNM2 | Intermediate CMT or CMT2, cataracts, ophthalmoplegia, ptosis |
Cerebrotendinous xanthomatosis (213700) | AR | CRP27A1 | See table 1a |
SPG9A (601162)/SPG9B (616586) | AD/AR | ALDH18A1 | See table 1b |
SPG46 (614409) | AR | GBA2 | See table 1b |
HLD5/HCC (610532) | AR | FAM126A | See table 1c |
(c) Cranial and peripheral neuropathy syndromes | |||
FAP-4 (105120) | AD | GSN | Corneal lattice dystrophy, cranial neuropathies, cutix laxa |
Kearns-Sayre syndrome (530000) | mDNA deletions | Ophthalmoplegia, retinitis pigmentosa, heart block, ptosis | |
MTDPS8B (612075) | AR | RRM2B | PEO, MNGIE, minimal neuropathy |
CFEOMA3 (600638) | AD | TUBB3 | Congenital strabismus, rarely isolated axonal sensory-motor neuropathy, dysgenesis of the corpus callosum, finger and wrist contractures, developmental delay, Kallmann syndrome |
SBMA (313200) | XL | AR | Motor neuropathy, facial fasciculations, tremor, androgen insensitivity |
BVVLS2 (614707) | AR | SLC52A2 | Facial and bulbar weakness, sensory ataxia, sensory-motor axonal neuropathy, optic atrophy, sensory neuronal hearing loss |
BVVLS1 (211530) | AR | SLC52A3 | Sensory neuronal hearing loss, facial and bulbar weakness, upper limb predominant motor neuropathy |
PNMHH (614369) | AR | MYH14 | Distal myopathy, motor axonal neuropathy, hoarseness, hearing loss |
Cowchock syndrome (310490) | X-linked | AIFM1 | Mental retardation (60%), deafness, slowly progressive sensory and axonal neuropathy from childhood |
MELAS (540000) | mitochondrial | MTTL1 m3243A>G | Myopathy, deafness, ophthalmoplegia, diabetes, stroke like episodes, predominantly sensory axonal neuropathy |
NF2 (101000) | AD | NF2 | Bilateral acoustic schwannomas. Axonal sensory-motor neuropathy |
Kanzaki disease (609242) | AR | NAGA | Adult-onset—diffuse angiokeratoma, sensory-neural hearing loss, recurrent episodes of vertigo, sensory-motor axonal neuropathy. Periventricular white matter abnormalities on MRI |
HSN1E (614116) | AD | DNMT1 | Dementia, deafness and sensory neuropathy |
ACPHD (616192) | AR | DNAJC3 | Deafness. See table 1a |
PHARC syndrome (612674) | AR | ABHD12 | Deafness. See table 1a |
Refsum’s disease (266500) | AR | PHYH | Deafness. See table 1a |
PBD9B (Refsum variant) (614879) | AR | PEX7 | Deafness. See table 1c |
MEDNIK (609313) | AR | AP1S1 | Deafness. See table 1c |
MTDPS5 (612073) | AR | SUCLA2 | Deafness. See table 1c |
MTDPS4B (613662) | AR | POLG | Deafness. See table 2a |
CMTX5 (311070) | X-linked | PRPS1 | Deafness. See table 2b |
(d) Endocrinopathy and neuropathy syndromes | |||
Gonadal dysgenesis with minifascicular neuropathy (607080) | AR | DHH | Gonadal dysgenesis, sensory-motor axonal neuropathy |
Adrenoleukodystrophy (300100) | XL | ABCD1 | Adrenal failure. See table 1b |
AAAS (231550) | AR | AAAS | Adrenal failure. See table 1c |
Infantile-onset multisystem neurological, endocrine and pancreatic disease (616263) | AR | PTRH2 | See table 1c |
SBMA (313200) | X-linked | AR | Androgen insensitivity. See table 2c |
(e) Musculoskeletal/myopathy and neuropathy syndromes | |||
Merosin-deficient congenital muscular dystrophy (MDC1A) (607855) | AR | LAMA2 | Congenital muscular dystrophy, mildly slowed PNS conduction, abnormal T2 MRI signal white matter |
MFM6 (612954) | AR | BAG3 | Giant axons on nerve biopsy, myofibrillar myopathy, cardiomyopathy, scoliosis, sensory-motor axonal neuropathy |
Limb girdle muscular dystrophy and neuropathy (181350) | AD | LMNA | Limb girdle muscular dystrophy, cardiomyopathy, sensory-motor axonal neuropathy |
MERRF (545000) | m8313G>A m8344A>G | MTTK | Myoclonic epilepsy, myopathy, lipoma, sensory axonal neuropathy |
Multiple acyl-CoA dehydrogenase deficiency (231680) | AR | ETFDH | Neonatal and late onset forms. hypoglycaemia, metabolic acidosis, and hepatomegaly often preceded by metabolic stress. Muscle involvement in the form of pain, weakness, and lipid storage myopathy also occur. Riboflavin responsive |
HMN2A (158590) | AD | HSPB8 | Distal hereditary motor neuropathy and proximal myopathy |
HMN2B (608634) | AD | HSPB1 | Distal hereditary motor neuropathy. Myopathic changes on muscle biopsy |
Lethal congenital contracture syndrome 7 (602346) | AR | CNTNAP1 | Congenital severe arthrogryposis multiplex congenital, demyelinating neuropathy |
PNMHH (614369) | AR | MYH14 | See table 2c |
(f) Cardiomyopathy and neuropathy syndromes | |||
FAP-1 (105210) | AD | TTR | Dysautonomia, cardiac disease carpel tunnel syndrome, painful sensory-motor axonal neuropathy, SNCV may mimic CIDP |
Fabry disease (301500) | X-linked | GLA | Angiokeratoma, painful sensory axonal and small fibre neuropathy, cardiomyopathy, renal failure |
Mitochondrial complex V deficiency (516070) | m8529G>A | MTATP8 | Hypertrophic cardiomyopathy, ataxia, PEO, dysarthria, sensory-motor axonal neuropathy |
NARP (551500) | Mitochondrial | MTATP6 | See table 1a |
Friedreich’s ataxia (229300) | AR | FXN | See table 1a |
HAYOS (617183) | AD | ATAD3A | See table 1c |
McLeod syndrome (300842) | XL | XK | See table 2a |
Kearns-Sayre syndrome (530000) | mitochondrial | See table 2b | |
MFM6 (612954) | AR | BAG3 | See table 2e |
(g) Hepatic, gastrointestinal and neuropathy syndromes | |||
Hepatic | |||
MTDPS3 (251880) | AR | DGUOK | Neonatal liver failure, myopathy, sensory-motor axonal neuropathy |
MTDPS6 (256810) | AR | MPV17 | Corneal opacification, neonatal liver failure, acromutilation, sensory axonal neuropathy |
SCAR21 (607982) | AR | SCYL1 | See table 1a |
Tyrosinemia type 1 (276700) | AR | FAH | See table 2h |
Gastrointestinal | |||
MTDPS1 (603041) | AR | TYMP | MNGIE: chronic pseudo-obstruction, sensory-motor neuropathy with slow conduction (may mimic CIDP), myopathic weakness, cachexia. Leukodystrophy on MRI |
MTDPS4B (613662) | AR | POLG | MNGIE: chronic pseudo-obstruction, axonal sensory ataxic neuropathy, myopathic weakness, cachexia. Normal brain MRI |
MTDPS8B (612075) | AR | RRM2B | PEO, MNGIE, minimal neuropathy |
Familial visceral amyloidosis (105200) | AD | B2M | Adult-onset chronic diarrhoea. Autonomic and sensory-motor axonal neuropathy |
Somatic and autonomic neuropathy | AD | PRNP | Autonomic and sensory axonal neuropathy preceding cognitive decline, chronic diarrhoea |
Goldberg-Shprintzen megacolon syndrome with associated sensory motor axonal neuropathy (609460) | AR | KIAA1279 | Intellectual disability, microcephaly, dysmorphic facies, Hirschsprung disease, pachygyria, cerebellar hypoplasia (defect in neural crest migration) |
Waardenburg syndrome type 2E (611584)/ PWCH (609136) | AD | SOX10 | Hypopigmentation of the hair and skin, sensory hearing loss, demyelinating neuropathy, dysmyelinating leukodystrophy, developmental delay, spasticity, ataxia, Hirschsprung disease |
AAAS (231550) | AR | AAAS | Achalasia. See table 1c |
MEDNIK (609313) | AR | AP1S1 | Congenital diarrhoea. See table 1c |
Cerebrotendinous xanthomatosis (213700) | AR | CRP27A1 | Congenital diarrhoea. See table 1c |
FAP-1 (105210) | AD | TTR | See table 2f |
(h) Renal failure and neuropathy syndromes | |||
FAP-3 (105200) | AD | APOA1 | Axonal sensory-motor neuropathy similar to TTR FAP, amyloid nephropathy |
Action myoclonus-renal failure syndrome (254900) | AR | SCARB2 | Progressive myoclonic epilepsy with preserved cognition, onset second decade, renal impairment, rarely demyelinating sensory-motor neuropathy (without renal failure) |
CMTDIE (614455) | AD | INF2 | Focal segmental glomerulonephritis and sensory-motor neuropathy with intermediate conduction velocities. |
Fabry disease (301500) | X-Linked | GLA | See table 2f |
MMACHC (277400) | AR | MMACHC | Thrombotic microangiopathy of kidneys. See table 2i |
(i) Haematological and immunological neuropathy syndromes | |||
MMACHC (277400) | AR | MMACHC | Onset infancy to adulthood; thrombotic thrombocytopenia with encephalopathy, myelopathy, renal and pulmonary complications (can be life threatening), retinitis pigmentosa, axonal motor neuropathy. Treated with high-dose vitamin B12 |
Chediak-Higashi syndrome (214500) | AR | LYST | Partial albinism, immunodeficiency, cerebellar atrophy, sensory-motor axonal neuropathy |
Early-onset chronic axonal neuropathy, strokes, and haemolysis: inherited CD59 deficiency (612300) | AR | CD59 | Onset first and second decade. Haemolytic anaemia, strokes and relapsing immune-mediated demyelinating neuropathy |
McLeod syndrome (300842) | X-Linked | XK | See table 2a |
(j) Skin and connective tissue and neuropathy syndromes | |||
Xeroderma pigmentosum (278700) | AR | XPA | Photosensitivity and increased risk of cutaneous malignancy, global developmental delay, deafness, sensory-motor axonal peripheral neuropathy |
HNARMD (608895) | AD | FBLN5 | Age-related macular degeneration, hyperelastic skin, demyelinating neuropathy also described |
EDS6 (225400) | AR | PLOD1 | Congenital hypotonia, joint laxity, scleral fragility, susceptibility to large vessel injury, mild sensory-motor axonal neuropathy |
Connective tissue disorder and peripheral neuropathy (130660) | AD | EMILIN1 | Aortic aneurysm, skin laxity and sensory-motor axonal neuropathy (single family reported) |
Refsum’s disease (266500) | AR | PHYH | Ichthyosis. See table 1a |
PBD9B (Refsum variant) (614879) | AR | PEX7 | Ichthyosis. See table 1a |
Cerebrotendinous xanthomatosis (213700) | AR | CRP27A1 | Xanthoma. See table 1a |
CEDNIK syndrome (609528) | AR | SNAP29 | Icthyosis and palmoplantar keratoderma. See table 1c |
MEDNIK (609313) | AR | AP1S1 | Icthyosis and palmoplantar keratoderma. See table 1c |
Cockayne syndrome (216400/133540) | AR | ERCC6/ERCC8 | Cutaneous photosensitivity. See table 1c |
FAP-4 (105120) | AD | GSN | Cutis laxa. See table 2c |
Kanzaki disease (609242) | AR | NAGA | Angiokeratoma. See table 2c |
Fabry disease (301500) | X-linked | GLA | Angiokeratoma. See table 2c |
(k) Relapsing complex inherited neuropathy syndromes | |||
Porphyria, acute intermittent (AIP) (176000) | AD | HMBS | Abdominal pain, psychosis, depression, seizures, axonal predominantly motor neuropathy |
Coproporphyria (121300) | AD | CPOX | Skin photosensitivity and haemolytic anaemia. Can present acutely similar to AIP |
Porphyria, variegata (176200) | AD | PPOX | Skin photosensitivity. Acute episodes similar to AIP |
Tyrosinemia type 1 (276700) | AR | FAH | Infantile or adolescent onset liver disease, renal tubular dysfunction and hypophosphatemic rickets. Acute episodes of neuropathy similar to AIP |
Trifunctional protein deficiency with myopathy and neuropathy (609015) | AR |
HADHA HADHB | Disorder of mitochondrial beta oxidation of fatty acids. Severe neonatal, infantile and late adolescent onset described, the latter characterised by a progressive myopathy with recurrent rhabdomyolysis and a sensory-motor axonal neuropathy. Abnormal urine organic acids |
Maple syrup urine disease Ib (248600) | AR | BCKDHB | Metabolic encephalopathy, elevated branched chain amino acids in urine, acute axonal neuropathy |
Thiamine metabolism dysfunction syndrome 4 THMD4 (613710) | AR | SLC25A19 | Acute encephalopathic episodes and paralysis following febrile illness with almost complete recovery. Absent sensory-motor action potential during illness. Bilateral striatal necrosis on MRI. Additional chronic progressive axonal neuropathy |
Tangier disease (205400) | AR | ABC1 | Multifocal relapsing mononeuropathies. Orange tonsils, organomegaly; pain, paraesthesias, anaesthesia |
Inherited CD59 deficiency (612300) | AR | CD59 | See table 2i |
Number in parenthesis is the OMIM phenotype number.
AR, autosomal recessive; AD, autosomal dominant; BVVL, Brown-Vialetto-Van Laere syndrome; CFEOMA3, fibrosis of extraocular muscles, congenital, 3A, with or without extraocular involvement; CSF, cerebrospinal fluid; EAO, Early age of onset; EDS, Ehlers-Danlos syndrome; FAP, familial amyloid polyneuropathy; FLAIR, Fluid-Attenuated Inversion Recovery; HMN, hereditary motor neuropathy; HNRAMD, neuropathy, hereditary, with or without age-related macular degeneration; MELAS, mitochondrial myopathy, encephalopathy; MERFF, myoclonic epilepsy associated with ragged red fibres; MFM, myofibrillar myopathy; MNGIE, mitochondrial neuro gastrointestinal encephalopathy; MTDPS, mitochondrial DNA depletion syndrome; NARP, neuropathy, ataxia, retinitis pigmentosa; NF2, neurofibromatosis type 2; OMIM, Online Mendelian Inheritance in Man; PEO, progressive external ophthalmoplegia; PNMHH, peripheral neuropathy, myopathy, hoarseness and hearing loss, lactic acidosis and stroke-like episodes; PWCH, peripheral demyelinating neuropathy, central demyelination, Waardenburg syndrome; SBMA, spinal bulbar muscular atrophy; SNCV, slow nerve conduction velocities.