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Spinal muscular atrophy, type II(SMA2)

MedGen UID:
95975
Concept ID:
C0393538
Disease or Syndrome
Synonyms: Muscular atrophy, spinal, infantile chronic form; Muscular atrophy, spinal, intermediate type; SMA 2; SMA II; SMA2; Spinal muscular atrophy type 2
SNOMED CT: SMA2 (128212001); Late infantile spinal muscular atrophy (128212001); Spinal muscular atrophy, type II (128212001); Spinal muscular atrophy type II (128212001)
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): SMN1 (5q13.2)
 
Monarch Initiative: MONDO:0009673
OMIM®: 253550
Orphanet: ORPHA83418

Disease characteristics

Excerpted from the GeneReview: Spinal Muscular Atrophy
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. [from GeneReviews]
Authors:
Thomas W Prior  |  Meganne E Leach  |  Erika Finanger   view full author information

Additional descriptions

From OMIM
Spinal muscular atrophy refers to a group of autosomal recessive neuromuscular disorders characterized by degeneration of the anterior horn cells of the spinal cord, leading to symmetric muscle weakness and atrophy (summary by Wirth, 2000).  http://www.omim.org/entry/253550
From MedlinePlus Genetics
Spinal muscular atrophy is a genetic disorder characterized by weakness and wasting (atrophy) in muscles used for movement (skeletal muscles). It is caused by a loss of specialized nerve cells, called motor neurons that control muscle movement. The weakness tends to be more severe in the muscles that are close to the center of the body (proximal) compared to muscles away from the body's center (distal). The muscle weakness usually worsens with age. There are many types of spinal muscular atrophy that are caused by changes in the same genes. The types differ in age of onset and severity of muscle weakness; however, there is overlap between the types. Other forms of spinal muscular atrophy and related motor neuron diseases, such as spinal muscular atrophy with progressive myoclonic epilepsy, spinal muscular atrophy with lower extremity predominance, X-linked infantile spinal muscular atrophy, and spinal muscular atrophy with respiratory distress type 1 are caused by mutations in other genes.

Spinal muscular atrophy type 0 is evident before birth and is the rarest and most severe form of the condition. Affected infants move less in the womb, and as a result they are often born with joint deformities (contractures). They have extremely weak muscle tone (hypotonia) at birth. Their respiratory muscles are very weak and they often do not survive past infancy due to respiratory failure. Some infants with spinal muscular atrophy type 0 also have heart defects that are present from birth (congenital).

Spinal muscular atrophy type I (also called Werdnig-Hoffmann disease) is the most common form of the condition. It is a severe form of the disorder with muscle weakness evident at birth or within the first few months of life. Most affected children cannot control their head movements or sit unassisted. Children with this type may have swallowing problems that can lead to difficulty feeding and poor growth. They can also have breathing problems due to weakness of respiratory muscles and an abnormally bell-shaped chest that prevents the lungs from fully expanding. Most children with spinal muscular atrophy type I do not survive past early childhood due to respiratory failure.

Spinal muscular atrophy type II (also called Dubowitz disease) is characterized by muscle weakness that develops in children between ages 6 and 12 months. Children with this type can sit without support, although they may need help getting to a seated position. However, as the muscle weakness worsens later in childhood, affected individuals may need support to sit. Individuals with spinal muscular atrophy type II cannot stand or walk unaided. They often have involuntary trembling (tremors) in their fingers, a spine that curves side-to-side (scoliosis), and respiratory muscle weakness that can be life-threatening. The life span of individuals with spinal muscular atrophy type II varies, but many people with this condition live into their twenties or thirties.

Spinal muscular atrophy type III (also called Kugelberg-Welander disease) typically causes muscle weakness after early childhood. Individuals with this condition can stand and walk unaided, but over time, walking and climbing stairs may become increasingly difficult. Many affected individuals require wheelchair assistance later in life. People with spinal muscular atrophy type III typically have a normal life expectancy.

Spinal muscular atrophy type IV is rare and often begins in early adulthood. Affected individuals usually experience mild to moderate muscle weakness, tremors, and mild breathing problems. People with spinal muscular atrophy type IV have a normal life expectancy.  https://medlineplus.gov/genetics/condition/spinal-muscular-atrophy

Clinical features

From HPO
Hand tremor
MedGen UID:
68689
Concept ID:
C0239842
Finding
An unintentional, oscillating to-and-fro muscle movement affecting the hand.
Degeneration of anterior horn cells
MedGen UID:
375215
Concept ID:
C1843505
Finding
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.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
EMG abnormality
MedGen UID:
99199
Concept ID:
C0476403
Finding
Abnormal results of investigations using electromyography (EMG).
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Tongue fasciculations
MedGen UID:
65987
Concept ID:
C0239548
Finding
Fasciculations or fibrillation affecting the tongue muscle.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Spinal muscular atrophy, type II in Orphanet.

Professional guidelines

PubMed

Coratti G, Lenkowicz J, Pera MC, D'Amico A, Bruno C, Gullì C, Brolatti N, Pedemonte M, Antonaci L, Ricci M, Capasso A, Cicala G, Cutrona C, de Sanctis R, Carnicella S, Forcina N, Cateruccia M, Damasio MB, Labianca L, Manfroni F, Leone A, Bertini E, Pane M, Patarnello S, Valentini V, Mercuri E
J Neurol Neurosurg Psychiatry 2024 Feb 14;95(3):235-240. doi: 10.1136/jnnp-2023-332084. PMID: 37739783
Coratti G, Pane M, Lucibello S, Pera MC, Pasternak A, Montes J, Sansone VA, Duong T, Dunaway Young S, Messina S, D'Amico A, Civitello M, Glanzman AM, Bruno C, Salmin F, Tacchetti P, Carnicella S, Sframeli M, Antonaci L, Frongia AL, De Vivo DC, Darras BT, Day J, Bertini E, Muntoni F, Finkel R, Mercuri E; iSMAC group
Neuromuscul Disord 2021 Jul;31(7):596-602. Epub 2021 Apr 2 doi: 10.1016/j.nmd.2021.03.012. PMID: 34099377
Brollier LD, Matuszczak M, Marri T, Carbajal JG, Moorman AT, Sorial EM, Jain R
Paediatr Anaesth 2021 Feb;31(2):160-166. Epub 2020 Dec 19 doi: 10.1111/pan.13964. PMID: 32623818

Curated

Rudnik-Schöneborn S, Eggermann T, Kress W, Lemmink HH, Cobben JM, Zerres K
Eur J Hum Genet 2012 Jun;20(6) Epub 2012 Apr 18 doi: 10.1038/ejhg.2012.62. PMID: 22510849Free PMC Article

American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Exon 7 Deletion (Pathogenic Variant) in Survival Motor Neuron Gene (SMN1), Spinal Muscular Atrophy (SMA), 2020

ACMG Carrier Screening ACT Sheet Spinal Muscular Atrophy (SMA)

Recent clinical studies

Etiology

Buchignani B, Cicala G, Moriconi F, Ricci M, Capasso A, Coratti G, Casiraghi J, Albamonte E, Cristofani P, Cutrona C, Pera MC, Antonaci L, Roncoroni C, Chieffo D, Sansone VA, Battini R, Pane M, Mercuri E
Neuromuscul Disord 2023 Oct;33(10):711-717. Epub 2023 Sep 9 doi: 10.1016/j.nmd.2023.08.005. PMID: 37709650
Ørngreen MC, Andersen AG, Eisum AS, Hald EJ, Raaschou-Pedersen DE, Løkken N, Høi-Hansen CE, Vissing J, Born AP, van Hall G
Acta Paediatr 2021 Dec;110(12):3367-3375. Epub 2021 Aug 30 doi: 10.1111/apa.16074. PMID: 34407566
Frongia AL, Natera-de Benito D, Ortez C, Alarcón M, Borrás A, Medina J, Vigo M, Padrós N, Moya O, Armas J, Carrera-García L, Expósito-Escudero J, Cuadras D, Bernal S, Martorell L, Colomer J, Nascimento A
Neuromuscul Disord 2019 Jul;29(7):517-524. Epub 2019 Apr 18 doi: 10.1016/j.nmd.2019.04.003. PMID: 31201046
van den Engel-Hoek L, Erasmus CE, van Bruggen HW, de Swart BJ, Sie LT, Steenks MH, de Groot IJ
Neurology 2009 Nov 24;73(21):1787-91. doi: 10.1212/WNL.0b013e3181c34aa6. PMID: 19933981
Messina S, Pane M, De Rose P, Vasta I, Sorleti D, Aloysius A, Sciarra F, Mangiola F, Kinali M, Bertini E, Mercuri E
Neuromuscul Disord 2008 May;18(5):389-93. Epub 2008 Apr 16 doi: 10.1016/j.nmd.2008.02.008. PMID: 18420410

Diagnosis

Fuller HR, Shorrock HK, Gillingwater TH, Pigott A, Smith V, Kulshrestha R, Sewry CS, Willis TA
J Neuromuscul Dis 2017;4(4):357-362. doi: 10.3233/JND-170260. PMID: 29172006
Bertoli S, De Amicis R, Mastella C, Pieri G, Giaquinto E, Battezzati A, Leone A, Baranello G
Clin Nutr 2017 Dec;36(6):1674-1680. Epub 2016 Nov 16 doi: 10.1016/j.clnu.2016.10.020. PMID: 27890489Free PMC Article
Davis RH, Miller EA, Zhang RZ, Swoboda KJ
J Pediatr 2015 Dec;167(6):1362-8.e1. Epub 2015 Oct 9 doi: 10.1016/j.jpeds.2015.09.023. PMID: 26454573Free PMC Article
van Bruggen HW, van den Engel-Hoek L, van der Pol WL, de Wijer A, de Groot IJ, Steenks MH
J Child Neurol 2011 Nov;26(11):1392-6. Epub 2011 May 18 doi: 10.1177/0883073811407696. PMID: 21596705
Vestergaard P, Glerup H, Steffensen BF, Rejnmark L, Rahbek J, Moseklide L
J Rehabil Med 2001 Jul;33(4):150-5. PMID: 11506212

Therapy

Brollier LD, Matuszczak M, Marri T, Carbajal JG, Moorman AT, Sorial EM, Jain R
Paediatr Anaesth 2021 Feb;31(2):160-166. Epub 2020 Dec 19 doi: 10.1111/pan.13964. PMID: 32623818
Frongia AL, Natera-de Benito D, Ortez C, Alarcón M, Borrás A, Medina J, Vigo M, Padrós N, Moya O, Armas J, Carrera-García L, Expósito-Escudero J, Cuadras D, Bernal S, Martorell L, Colomer J, Nascimento A
Neuromuscul Disord 2019 Jul;29(7):517-524. Epub 2019 Apr 18 doi: 10.1016/j.nmd.2019.04.003. PMID: 31201046
Seferian AM, Moraux A, Canal A, Decostre V, Diebate O, Le Moing AG, Gidaro T, Deconinck N, Van Parys F, Vereecke W, Wittevrongel S, Annoussamy M, Mayer M, Maincent K, Cuisset JM, Tiffreau V, Denis S, Jousten V, Quijano-Roy S, Voit T, Hogrel JY, Servais L
PLoS One 2015;10(4):e0121799. Epub 2015 Apr 10 doi: 10.1371/journal.pone.0121799. PMID: 25861036Free PMC Article
Kirschner J, Schorling D, Hauschke D, Rensing-Zimmermann C, Wein U, Grieben U, Schottmann G, Schara U, Konrad K, Müller-Felber W, Thiele S, Wilichowski E, Hobbiebrunken E, Stettner GM, Korinthenberg R
Neuromuscul Disord 2014 Feb;24(2):134-42. Epub 2013 Nov 13 doi: 10.1016/j.nmd.2013.10.011. PMID: 24300782
Zerres K, Rudnik-Schöneborn S, Forrest E, Lusakowska A, Borkowska J, Hausmanowa-Petrusewicz I
J Neurol Sci 1997 Feb 27;146(1):67-72. doi: 10.1016/s0022-510x(96)00284-5. PMID: 9077498

Prognosis

Bertoli S, De Amicis R, Mastella C, Pieri G, Giaquinto E, Battezzati A, Leone A, Baranello G
Clin Nutr 2017 Dec;36(6):1674-1680. Epub 2016 Nov 16 doi: 10.1016/j.clnu.2016.10.020. PMID: 27890489Free PMC Article
Chou SH, Lin GT, Shen PC, Lue YJ, Lu CC, Tien YC, Lu YM
Eur Spine J 2017 Jun;26(6):1721-1731. Epub 2016 Nov 2 doi: 10.1007/s00586-016-4828-2. PMID: 27807779
Davis RH, Miller EA, Zhang RZ, Swoboda KJ
J Pediatr 2015 Dec;167(6):1362-8.e1. Epub 2015 Oct 9 doi: 10.1016/j.jpeds.2015.09.023. PMID: 26454573Free PMC Article
Fujak A, Raab W, Schuh A, Richter S, Forst R, Forst J
BMC Musculoskelet Disord 2013 Oct 4;14:283. doi: 10.1186/1471-2474-14-283. PMID: 24093531Free PMC Article
Glanzman AM, O'Hagen JM, McDermott MP, Martens WB, Flickinger J, Riley S, Quigley J, Montes J, Dunaway S, Deng L, Chung WK, Tawil R, Darras BT, De Vivo DC, Kaufmann P, Finkel RS; Pediatric Neuromuscular Clinical Research Network for Spinal Muscular Atrophy (PNCR); Muscle Study Group (MSG)
J Child Neurol 2011 Dec;26(12):1499-507. Epub 2011 Sep 21 doi: 10.1177/0883073811420294. PMID: 21940700

Clinical prediction guides

Buchignani B, Cicala G, Moriconi F, Ricci M, Capasso A, Coratti G, Casiraghi J, Albamonte E, Cristofani P, Cutrona C, Pera MC, Antonaci L, Roncoroni C, Chieffo D, Sansone VA, Battini R, Pane M, Mercuri E
Neuromuscul Disord 2023 Oct;33(10):711-717. Epub 2023 Sep 9 doi: 10.1016/j.nmd.2023.08.005. PMID: 37709650
Frongia AL, Natera-de Benito D, Ortez C, Alarcón M, Borrás A, Medina J, Vigo M, Padrós N, Moya O, Armas J, Carrera-García L, Expósito-Escudero J, Cuadras D, Bernal S, Martorell L, Colomer J, Nascimento A
Neuromuscul Disord 2019 Jul;29(7):517-524. Epub 2019 Apr 18 doi: 10.1016/j.nmd.2019.04.003. PMID: 31201046
Fuller HR, Shorrock HK, Gillingwater TH, Pigott A, Smith V, Kulshrestha R, Sewry CS, Willis TA
J Neuromuscul Dis 2017;4(4):357-362. doi: 10.3233/JND-170260. PMID: 29172006
Bertoli S, De Amicis R, Mastella C, Pieri G, Giaquinto E, Battezzati A, Leone A, Baranello G
Clin Nutr 2017 Dec;36(6):1674-1680. Epub 2016 Nov 16 doi: 10.1016/j.clnu.2016.10.020. PMID: 27890489Free PMC Article
van Bruggen HW, van den Engel-Hoek L, van der Pol WL, de Wijer A, de Groot IJ, Steenks MH
J Child Neurol 2011 Nov;26(11):1392-6. Epub 2011 May 18 doi: 10.1177/0883073811407696. PMID: 21596705

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG ACT, 2020
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Exon 7 Deletion (Pathogenic Variant) in Survival Motor Neuron Gene (SMN1), Spinal Muscular Atrophy (SMA), 2020
    • ACMG ACT, 2018
      ACMG Carrier Screening ACT Sheet Spinal Muscular Atrophy (SMA)
    • EuroGenetest, 2012
      Clinical utility gene card for: proximal spinal muscular atrophy.

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