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Autosomal recessive distal spinal muscular atrophy 2(HMNJ; DSMA2)

MedGen UID:
344189
Concept ID:
C1854023
Disease or Syndrome
Synonyms: Hereditary motor neuropathy, Jerash type; Motor neuropathy, distal, Jerash type; NEURONOPATHY, DISTAL HEREDITARY MOTOR, JERASH TYPE; NEUROPATHY, DISTAL HEREDITARY MOTOR, AUTOSOMAL RECESSIVE 2; NEUROPATHY, DISTAL HEREDITARY MOTOR, JERASH TYPE; Spinal muscular atrophy, Jerash type
SNOMED CT: Autosomal recessive distal spinal muscular atrophy type 2 (763533003); Distal hereditary motor neuropathy Jerash type (763533003)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): SIGMAR1 (9p13.3)
 
Monarch Initiative: MONDO:0011585
OMIM®: 605726
Orphanet: ORPHA139552

Definition

Autosomal recessive distal hereditary motor neuronopathy-2 (HMNR2) is a neuromuscular disorder characterized by onset of distal muscle weakness and wasting affecting the lower and upper limbs in the first decade; there is no sensory involvement (summary by Li et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive HMN, see HMNR1 (604320). [from OMIM]

Clinical features

From HPO
Absent Achilles reflex
MedGen UID:
108240
Concept ID:
C0558845
Finding
Absence of the Achilles reflex (also known as the ankle jerk reflex), which can normally be elicited by tapping the tendon is tapped while the foot is dorsiflexed.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
Hammertoe
MedGen UID:
209712
Concept ID:
C1136179
Anatomical Abnormality
Hyperextension of the metatarsal-phalangeal joint with hyperflexion of the proximal interphalangeal (PIP) joint.
Foot dorsiflexor weakness
MedGen UID:
356163
Concept ID:
C1866141
Finding
Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Hyperactive patellar reflex
MedGen UID:
66003
Concept ID:
C0240116
Finding
Decreased motor nerve conduction velocity
MedGen UID:
388130
Concept ID:
C1858729
Finding
A type of decreased nerve conduction velocity that affects the motor neuron.
Decreased compound muscle action potential amplitude
MedGen UID:
908357
Concept ID:
C4230625
Finding
Reduced level of the compound muscle action potential (CMAP), which is recorded following electrical stimulation of a nerve from surface electrodes overlying a muscle supplied by that nerve.
Spinal muscular atrophy
MedGen UID:
7755
Concept ID:
C0026847
Disease or Syndrome
Spinal muscular atrophy (SMA) is characterized by muscle weakness and atrophy resulting from progressive degeneration and irreversible loss of the anterior horn cells in the spinal cord (i.e., lower motor neurons) and the brain stem nuclei. The onset of weakness ranges from before birth to adulthood. The weakness is symmetric, proximal > distal, and progressive. Before the genetic basis of SMA was understood, it was classified into clinical subtypes based on maximum motor function achieved; however, it is now apparent that the phenotype of SMN1-associated SMA spans a continuum without clear delineation of subtypes. With supportive care only, poor weight gain with growth failure, restrictive lung disease, scoliosis, and joint contractures are common complications; however, newly available targeted treatment options are changing the natural history of this disease.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Claw hand deformity
MedGen UID:
1814631
Concept ID:
C5702555
Anatomical Abnormality
An abnormality of the hand characterized by metacarpophalangeal (MCP) hyperextension and proximal interphalangeal (PIP) and distal interphalangeal (DIP) flexion. The position of the affected hand is said to resemble a claw.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAutosomal recessive distal spinal muscular atrophy 2
Follow this link to review classifications for Autosomal recessive distal spinal muscular atrophy 2 in Orphanet.

Professional guidelines

PubMed

Nishio H, Niba ETE, Saito T, Okamoto K, Takeshima Y, Awano H
Int J Mol Sci 2023 Jul 26;24(15) doi: 10.3390/ijms241511939. PMID: 37569314Free PMC Article
Łusakowska A, Wójcik A, Frączek A, Aragon-Gawińska K, Potulska-Chromik A, Baranowski P, Nowak R, Rosiak G, Milczarek K, Konecki D, Gierlak-Wójcicka Z, Burlewicz M, Kostera-Pruszczyk A
Orphanet J Rare Dis 2023 Aug 4;18(1):230. doi: 10.1186/s13023-023-02769-4. PMID: 37542300Free PMC Article
Hjartarson HT, Nathorst-Böös K, Sejersen T
Drug Des Devel Ther 2022;16:1865-1883. Epub 2022 Jun 16 doi: 10.2147/DDDT.S214174. PMID: 35734367Free PMC Article

Recent clinical studies

Etiology

Landfeldt E, Abner S, Pechmann A, Sejersen T, McMillan HJ, Lochmüller H, Kirschner J
Pharmacoeconomics 2023 Mar;41(3):275-293. Epub 2022 Dec 14 doi: 10.1007/s40273-022-01197-9. PMID: 36515815
Zambon AA, Pini V, Bosco L, Falzone YM, Munot P, Muntoni F, Previtali SC
Brain 2023 Mar 1;146(3):806-822. doi: 10.1093/brain/awac452. PMID: 36445400Free PMC Article
Paik J
CNS Drugs 2022 Apr;36(4):401-410. Epub 2022 Mar 13 doi: 10.1007/s40263-022-00910-8. PMID: 35284988
Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, Chiriboga CA, Saito K, Servais L, Tizzano E, Topaloglu H, Tulinius M, Montes J, Glanzman AM, Bishop K, Zhong ZJ, Gheuens S, Bennett CF, Schneider E, Farwell W, De Vivo DC; ENDEAR Study Group
N Engl J Med 2017 Nov 2;377(18):1723-1732. doi: 10.1056/NEJMoa1702752. PMID: 29091570
Talbot K, Davies KE
Semin Neurol 2001 Jun;21(2):189-97. doi: 10.1055/s-2001-15264. PMID: 11442327

Diagnosis

Nishio H, Niba ETE, Saito T, Okamoto K, Takeshima Y, Awano H
Int J Mol Sci 2023 Jul 26;24(15) doi: 10.3390/ijms241511939. PMID: 37569314Free PMC Article
Zambon AA, Pini V, Bosco L, Falzone YM, Munot P, Muntoni F, Previtali SC
Brain 2023 Mar 1;146(3):806-822. doi: 10.1093/brain/awac452. PMID: 36445400Free PMC Article
Hjartarson HT, Nathorst-Böös K, Sejersen T
Drug Des Devel Ther 2022;16:1865-1883. Epub 2022 Jun 16 doi: 10.2147/DDDT.S214174. PMID: 35734367Free PMC Article
Paik J
CNS Drugs 2022 Apr;36(4):401-410. Epub 2022 Mar 13 doi: 10.1007/s40263-022-00910-8. PMID: 35284988
Talbot K, Davies KE
Semin Neurol 2001 Jun;21(2):189-97. doi: 10.1055/s-2001-15264. PMID: 11442327

Therapy

Łusakowska A, Wójcik A, Frączek A, Aragon-Gawińska K, Potulska-Chromik A, Baranowski P, Nowak R, Rosiak G, Milczarek K, Konecki D, Gierlak-Wójcicka Z, Burlewicz M, Kostera-Pruszczyk A
Orphanet J Rare Dis 2023 Aug 4;18(1):230. doi: 10.1186/s13023-023-02769-4. PMID: 37542300Free PMC Article
Paik J
CNS Drugs 2022 Apr;36(4):401-410. Epub 2022 Mar 13 doi: 10.1007/s40263-022-00910-8. PMID: 35284988
Lefebvre S, Sarret C
Arch Pediatr 2020 Dec;27(7S):7S3-7S8. doi: 10.1016/S0929-693X(20)30269-4. PMID: 33357595
Arnold ES, Fischbeck KH
Handb Clin Neurol 2018;148:591-601. doi: 10.1016/B978-0-444-64076-5.00038-7. PMID: 29478602
Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, Chiriboga CA, Saito K, Servais L, Tizzano E, Topaloglu H, Tulinius M, Montes J, Glanzman AM, Bishop K, Zhong ZJ, Gheuens S, Bennett CF, Schneider E, Farwell W, De Vivo DC; ENDEAR Study Group
N Engl J Med 2017 Nov 2;377(18):1723-1732. doi: 10.1056/NEJMoa1702752. PMID: 29091570

Prognosis

Hjartarson HT, Nathorst-Böös K, Sejersen T
Drug Des Devel Ther 2022;16:1865-1883. Epub 2022 Jun 16 doi: 10.2147/DDDT.S214174. PMID: 35734367Free PMC Article
Saladini M, Nizzardo M, Govoni A, Taiana M, Bresolin N, Comi GP, Corti S
J Cell Mol Med 2020 Jan;24(2):1169-1178. Epub 2019 Dec 4 doi: 10.1111/jcmm.14874. PMID: 31802621Free PMC Article
Rao VK, Kapp D, Schroth M
J Manag Care Spec Pharm 2018 Dec;24(12-a Suppl):S3-S16. doi: 10.18553/jmcp.2018.24.12-a.s3. PMID: 30582825Free PMC Article
Talbot K, Davies KE
Semin Neurol 2001 Jun;21(2):189-97. doi: 10.1055/s-2001-15264. PMID: 11442327
Wirth B
Hum Mutat 2000;15(3):228-37. doi: 10.1002/(SICI)1098-1004(200003)15:3<228::AID-HUMU3>3.0.CO;2-9. PMID: 10679938

Clinical prediction guides

Łusakowska A, Wójcik A, Frączek A, Aragon-Gawińska K, Potulska-Chromik A, Baranowski P, Nowak R, Rosiak G, Milczarek K, Konecki D, Gierlak-Wójcicka Z, Burlewicz M, Kostera-Pruszczyk A
Orphanet J Rare Dis 2023 Aug 4;18(1):230. doi: 10.1186/s13023-023-02769-4. PMID: 37542300Free PMC Article
Lejman J, Zieliński G, Gawda P, Lejman M
Genes (Basel) 2021 Aug 28;12(9) doi: 10.3390/genes12091346. PMID: 34573328Free PMC Article
Ali HG, Ibrahim K, Elsaid MF, Mohamed RB, Abeidah MIA, Al Rawwas AO, Elshafey K, Almulla H, El-Akouri K, Almulla M, Othman A, Musa S, Al-Mesaifri F, Ali R, Shahbeck N, Al-Mureikhi M, Alsulaiman R, Alkaabi S, Ben-Omran T
Gene Ther 2021 Nov;28(10-11):676-680. Epub 2021 Jul 19 doi: 10.1038/s41434-021-00273-7. PMID: 34276047Free PMC Article
Lefebvre S, Sarret C
Arch Pediatr 2020 Dec;27(7S):7S3-7S8. doi: 10.1016/S0929-693X(20)30269-4. PMID: 33357595
Wirth B
Hum Mutat 2000;15(3):228-37. doi: 10.1002/(SICI)1098-1004(200003)15:3<228::AID-HUMU3>3.0.CO;2-9. PMID: 10679938

Recent systematic reviews

Landfeldt E, Abner S, Pechmann A, Sejersen T, McMillan HJ, Lochmüller H, Kirschner J
Pharmacoeconomics 2023 Mar;41(3):275-293. Epub 2022 Dec 14 doi: 10.1007/s40273-022-01197-9. PMID: 36515815
Paracha N, Hudson P, Mitchell S, Sutherland CS
Pharmacoeconomics 2022 Apr;40(Suppl 1):11-38. Epub 2021 Nov 11 doi: 10.1007/s40273-021-01105-7. PMID: 34761360Free PMC Article
Albrechtsen SS, Born AP, Boesen MS
Dan Med J 2020 Aug 7;67(9) PMID: 32800069
Li C, Geng Y, Zhu X, Zhang L, Hong Z, Guo X, Xia C
Medicine (Baltimore) 2020 Jan;99(5):e18975. doi: 10.1097/MD.0000000000018975. PMID: 32000428Free PMC Article
Zanetta C, Nizzardo M, Simone C, Monguzzi E, Bresolin N, Comi GP, Corti S
Clin Ther 2014 Jan 1;36(1):128-40. Epub 2013 Dec 17 doi: 10.1016/j.clinthera.2013.11.006. PMID: 24360800

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