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Spinal muscular atrophy with lower extremity predominance

MedGen UID:: 946178
•Concept ID:: CN263150
•: Disease or Syndrome

Synonym:	Autosomal dominant childhood-onset proximal spinal muscular atrophy
Modes of inheritance:	Autosomal dominant inheritance MedGen UID: 141047 •Concept ID: C0443147 • 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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Autosomal dominant inheritance (Orphanet)

Monarch Initiative:	MONDO:0018190
OMIM® Phenotypic series:	PS158600
Orphanet:	ORPHA363447

Definition

A rare genetic neuromuscular disease characterized by early onset muscular weakness with predominant proximal lower limb involvement. The disorder is static or only mildly progressive. The severity of manifestations ranges from lethal, congenital muscular atrophy with arthrogryposis to asymptomatic with subclinical features. [from ORDO]

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

Spinal muscular atrophy with lower extremity predominance

Autosomal dominant proximal spinal muscular atrophy
- Spinal muscular atrophy with lower extremity predominance
  - Autosomal dominant childhood-onset proximal spinal muscular atrophy with contractures
  - Autosomal dominant childhood-onset proximal spinal muscular atrophy without contractures

Recent clinical studies

Etiology

Autosomal dominant spinal muscular atrophy with lower extremity predominance: A recognizable phenotype of BICD2 mutations.

Rudnik-Schöneborn S, Deden F, Eggermann K, Eggermann T, Wieczorek D, Sellhaus B, Yamoah A, Goswami A, Claeys KG, Weis J, Zerres K
Muscle Nerve 2016 Sep;54(3):496-500. Epub 2016 Jul 9 doi: 10.1002/mus.25114. PMID: 26998597

Novel mutations expand the clinical spectrum of DYNC1H1-associated spinal muscular atrophy.

Scoto M, Rossor AM, Harms MB, Cirak S, Calissano M, Robb S, Manzur AY, Martínez Arroyo A, Rodriguez Sanz A, Mansour S, Fallon P, Hadjikoumi I, Klein A, Yang M, De Visser M, Overweg-Plandsoen WC, Baas F, Taylor JP, Benatar M, Connolly AM, Al-Lozi MT, Nixon J, de Goede CG, Foley AR, Mcwilliam C, Pitt M, Sewry C, Phadke R, Hafezparast M, Chong WK, Mercuri E, Baloh RH, Reilly MM, Muntoni F
Neurology 2015 Feb 17;84(7):668-79. Epub 2015 Jan 21 doi: 10.1212/WNL.0000000000001269. PMID: 25609763 Free PMC Article

See all (2)

Diagnosis

Expanding the phenotype of DYNC1H1-associated diseases with a rare variant resulting in spinal muscular atrophy with lower extremity predominance (SMA-LED) and upper motor neuron signs.

Lee J, Millington P, Dayasiri K, Ramdas S, Jayawant S, Anand G
Turk J Pediatr 2023;65(3):531-535. doi: 10.24953/turkjped.2022.513. PMID: 37395972

Late adult-onset spinal muscular atrophy with lower extremity predominance (SMALED).

Aziz I, Davis M, Liang C
BMJ Case Rep 2022 Mar 30;15(3) doi: 10.1136/bcr-2021-248297. PMID: 35354563 Free PMC Article

A recurrent de novo DYNC1H1 tail domain mutation causes spinal muscular atrophy with lower extremity predominance, learning difficulties and mild brain abnormality.

Chan SHS, van Alfen N, Thuestad IJ, Ip J, Chan AO, Mak C, Chung BH, Verrips A, Kamsteeg EJ
Neuromuscul Disord 2018 Sep;28(9):750-756. Epub 2018 Jul 20 doi: 10.1016/j.nmd.2018.07.002. PMID: 30122514

Exome Sequencing Identifies DYNC1H1 Variant Associated With Vertebral Abnormality and Spinal Muscular Atrophy With Lower Extremity Predominance.

Punetha J, Monges S, Franchi ME, Hoffman EP, Cirak S, Tesi-Rocha C
Pediatr Neurol 2015 Feb;52(2):239-44. Epub 2014 Oct 5 doi: 10.1016/j.pediatrneurol.2014.09.003. PMID: 25484024 Free PMC Article

Dominant spinal muscular atrophy with lower extremity predominance: linkage to 14q32.

Harms MB, Allred P, Gardner R Jr, Fernandes Filho JA, Florence J, Pestronk A, Al-Lozi M, Baloh RH
Neurology 2010 Aug 10;75(6):539-46. doi: 10.1212/WNL.0b013e3181ec800c. PMID: 20697106 Free PMC Article

See all (6)

Prognosis

Late adult-onset spinal muscular atrophy with lower extremity predominance (SMALED).

Aziz I, Davis M, Liang C
BMJ Case Rep 2022 Mar 30;15(3) doi: 10.1136/bcr-2021-248297. PMID: 35354563 Free PMC Article

Exome Sequencing Identifies De Novo DYNC1H1 Mutations Associated With Distal Spinal Muscular Atrophy and Malformations of Cortical Development.

Chen Y, Xu Y, Li G, Li N, Yu T, Yao RE, Wang X, Shen Y, Wang J
J Child Neurol 2017 Mar;32(4):379-386. Epub 2016 Dec 20 doi: 10.1177/0883073816683083. PMID: 28193117

See all (2)

Clinical prediction guides

A human dynein heavy chain mutation impacts cortical progenitor cells causing developmental defects, reduced brain size and altered brain architecture.

Romero DM, Zaidi D, Cifuentes-Diaz C, Maillard C, Grannec G, Selloum M, Birling MC, Bahi-Buisson N, Francis F
Neurobiol Dis 2023 May;180:106085. Epub 2023 Mar 16 doi: 10.1016/j.nbd.2023.106085. PMID: 36933672

DYNC1H1 mutations associated with neurological diseases compromise processivity of dynein-dynactin-cargo adaptor complexes.

Hoang HT, Schlager MA, Carter AP, Bullock SL
Proc Natl Acad Sci U S A 2017 Feb 28;114(9):E1597-E1606. Epub 2017 Feb 14 doi: 10.1073/pnas.1620141114. PMID: 28196890 Free PMC Article

Exome Sequencing Identifies De Novo DYNC1H1 Mutations Associated With Distal Spinal Muscular Atrophy and Malformations of Cortical Development.

Chen Y, Xu Y, Li G, Li N, Yu T, Yao RE, Wang X, Shen Y, Wang J
J Child Neurol 2017 Mar;32(4):379-386. Epub 2016 Dec 20 doi: 10.1177/0883073816683083. PMID: 28193117

Dynein mutations associated with hereditary motor neuropathies impair mitochondrial morphology and function with age.

Eschbach J, Sinniger J, Bouitbir J, Fergani A, Schlagowski AI, Zoll J, Geny B, René F, Larmet Y, Marion V, Baloh RH, Harms MB, Shy ME, Messadeq N, Weydt P, Loeffler JP, Ludolph AC, Dupuis L
Neurobiol Dis 2013 Oct;58:220-30. Epub 2013 Jun 4 doi: 10.1016/j.nbd.2013.05.015. PMID: 23742762 Free PMC Article

Dominant spinal muscular atrophy with lower extremity predominance: linkage to 14q32.

See all (6)

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Spinal muscular atrophy with lower extremity predominance

Definition

Term Hierarchy

Recent clinical studies

Etiology

Diagnosis

Prognosis

Clinical prediction guides

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