Top

Published in:

18-10-2023 | Myopathy | Original Article

Marked neuropsychiatric involvement and dysmorphic features in nemaline myopathy

Authors: Paulo Ribeiro Nóbrega, Jorge Luiz de Brito de Souza, Rebeca Bessa Maurício, Anderson Rodrigues Brandão de Paiva, Daniel Aguiar Dias, Clara Gontijo Camelo, Edmar Zanotelli, David Schlesinger, Pedro Braga-Neto, Cristiane Araujo Martins Moreno

Published in: Neurological Sciences | Issue 3/2024

Abstract

Background

Inherited nemaline myopathy is one of the most common congenital myopathies. This genetically heterogeneous disease is defined by the presence of nemaline bodies in muscle biopsy. The phenotypic spectrum is wide and cognitive involvement has been reported, although not extensively evaluated.

Methods

We report two nemaline myopathy patients presenting pronounced central nervous system involvement leading to functional compromise and novel facial and skeletal dysmorphic findings, possibly expanding the disease phenotype.

Results

One patient had two likely pathogenic NEB variants, c.2943G > A and c.8889 + 1G > A, and presented cognitive impairment and dysmorphic features, and the other had one pathogenic variant in ACTA1, c.169G > C (p.Gly57Arg), presenting autism spectrum disorder and corpus callosum atrophy. Both patients had severe cognitive involvement despite milder motor dysfunction.

Conclusion

We raise the need for further studies regarding the role of thin filament proteins in the central nervous system and for a systematic cognitive assessment of congenital myopathy patients.

Wallgren-Pettersson C, Sewry CA, Nowak KJ, Laing NG (2011) Nemaline myopathies. Seminars Paediatr Neurol 18(4):230–238. https://doi.org/10.1016/j.spen.2011.10.004CrossRef

Amburgey K, Acker M, Saeed S, Amin R, Beggs AH, Bönnemann CG et al (2021) A cross-sectional study of nemaline myopathy. Neurol 96(10):e1425–e1436. https://doi.org/10.1212/WNL.0000000000011458CrossRef

Moreno CAM, Abath Neto O, Donkervoort S, Hu Y, Reed UC, Oliveira ASB et al (2017) Clinical and histologic findings in ACTA1-related nemaline myopathy: case series and review of the literature. Pediatr Neurol 75:11–16. https://doi.org/10.1016/j.pediatrneurol.2017.04.002CrossRefPubMed

Ryan MM, Schnell C, Strickland CD, Shield LK, Morgan G, Iannaccone ST et al (2001) Nemaline myopathy: a clinical study of 143 cases. Ann Neurol 50(3):312–320. https://doi.org/10.1002/ana.1080CrossRefPubMed

Wang K, Li M, Hakonarson H (2010) ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res 38(16):e164–e164. https://doi.org/10.1093/nar/gkq603CrossRefPubMedPubMedCentral

McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GRS, Thormann A et al (2016) The ensemble variant effect predictor. Genome Biol 17(122):1–14. https://doi.org/10.1186/s13059-016-0974-4CrossRef

Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I et al (2005) The Montreal cognitive assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc 53(4):695–699. https://doi.org/10.1111/j.1532-5415.2005.53221.xCrossRefPubMed

Pike NA, Poulsen MK, Woo MA (2017) Validity of the Montreal cognitive assessment screener in adolescents and young adults with and without congenital heart disease. Nurs Res 66(3):222–230. https://doi.org/10.1097/NNR.0000000000000192CrossRefPubMedPubMedCentral

Schopler E, Reichler RJ, DeVellis RF, Daly K (1980) Toward objective classification of childhood autism: childhood autism rating scale (CARS). J Autism Dev Disord 10(1):91–103. https://doi.org/10.1007/BF02408436CrossRefPubMed

10.

Lehtokari VL, Kiiski K, Sandaradura SA, Laporte J, Repo P, Frey JA et al (2014) Mutation update: the spectra of nebulin variants and associated myopathies. Hum Mutat 35(12):1418–1926. https://doi.org/10.1002/humu.22693CrossRefPubMedPubMedCentral

11.

Banihani R, Smile S, Yoon G, Dupuis A, Mosleh M, Snider A et al (2015) Cognitive and neurobehavioral profile in boys with duchenne muscular dystrophy. J Child Neurol 30(11):1472–1482. https://doi.org/10.1177/0883073815570154CrossRefPubMed

12.

Douniol M, Jacquette A, Cohen D, Bodeau N, Rachidi L, Angeard N et al (2012) Psychiatric and cognitive phenotype of childhood myotonic dystrophy type 1. Dev Med Child Neurol 54(10):905–911. https://doi.org/10.1111/j.1469-8749.2012.04379.xCrossRefPubMed

13.

Brun BN, Mockler SRH, Laubscher KM, Stephan CM, Wallace AM, Collison JA, et al (2017) Comparison of brain MRI findings with language and motor function in the dystroglycanopathies. Neurology 88(7):623–629. https://doi.org/10.1212/WNL.0000000000003609

14.

Specht S, Straub V (2021) Intellectual disability in paediatric patients with genetic muscle diseases. Neuromuscul Disord 31(10):988–997. https://doi.org/10.1016/j.nmd.2021.08.012CrossRefPubMed

15.

Wallgren-Pettersson C (1989) Congenital nemaline myopathy: a clinical follow-up of twelve patients. J Neurol Sci 89(1):1–14. https://doi.org/10.1016/0022-510x(89)90002-6CrossRefPubMed

16.

Moreno CAM, Artilheiro MC, Fonseca ATQSM, Camelo CG, de Medeiros GC, Sassi FC et al (2023) Clinical manifestation of nebulin-associated nemaline myopathy. Neurol Genet 9(1):1–10. https://doi.org/10.1212/NXG.0000000000200056

17.

Saito Y, Komaki H, Hattori A, Takeuchi F, Sasaki M, Kawabata K et al (2011) Extramuscular manifestations in children with severe congenital myopathy due to ACTA1 gene mutations. Neuromuscul Disord 21(7):489–493. https://doi.org/10.1016/j.nmd.2011.03.004CrossRefPubMed

18.

Shmueli O, Horn-Saban S, Chalifa-Caspi V, Shmoish M, Ophir R, Benjamin-Rodrig H et al (2003) GeneNote: whole genome expression profiles in normal human tissues C R Biol 326(10,11):1067–1072. https://doi.org/10.1016/j.crvi.2003.09.012

19.

Kalajzic I, Kalajzic Z, Wang L, Jiang X, Lamothe K, San Miguel SM et al (2007) Pericyte/myoblast phenotype of osteoprogenitor cell. J Musculoskelet Neuronal Interact 7(4):320–322PubMed

20.

Chandra M, Mamidi R, Ford S, Hidalgo C, Witt C, Ottenheijm C et al (2009) Nebulin alters cross-bridge cycling kinetics and increases thin filament activation: a novel mechanism for increasing tension and reducing tension cost. J Biol Chem 284(45):30889–30896. https://doi.org/10.1074/jbc.M109.049718CrossRefPubMedPubMedCentral

21.

Laitila J, Hanif M, Paetau A, Hujanen S, Keto J, Somervuo P et al (2012) Expression of multiple nebulin isoforms in human skeletal muscle and brain. Muscle Nerve 46(5):730–777CrossRefPubMed

22.

Blokhuis AM, Deenen JCW, Voermans NC, van Engelen BGM, Kievit W, Groothuis JT (2021) The socioeconomic burden of facioscapulohumeral muscular dystrophy. J Neurol 268(12):4778–4788. https://doi.org/10.1007/s00415-021-10591-wCrossRefPubMedPubMedCentral

23.

Gaugler T, Klei L, Sanders SJ, Bodea CA, Goldberg AP, Lee AB et al (2014) Most genetic risk for autism resides with common variation. Nat Genet 46(8):881–885. https://doi.org/10.1038/ng.3039CrossRefPubMedPubMedCentral

24.

Astrea G, Battini R, Lenzi S, Frosini S, Bonetti S, Moretti E et al (2016) Learning disabilities in neuromuscular disorders: a springboard for adult life. Acta Myol 35(2):90–95PubMedPubMedCentral

25.

D’Angelo MG, Bresolin N (2006) Cognitive impairment in neuromuscular disorders. Muscle Nerve 34(1):16–33. https://doi.org/10.1002/mus.20535CrossRefPubMed

Title: Marked neuropsychiatric involvement and dysmorphic features in nemaline myopathy
Authors: Paulo Ribeiro Nóbrega
Jorge Luiz de Brito de Souza
Rebeca Bessa Maurício
Anderson Rodrigues Brandão de Paiva
Daniel Aguiar Dias
Clara Gontijo Camelo
Edmar Zanotelli
David Schlesinger
Pedro Braga-Neto
Cristiane Araujo Martins Moreno
Publication date: 18-10-2023
Publisher: Springer International Publishing
Keywords: Myopathy
Autism Spectrum Disorder
Published in: Neurological Sciences / Issue 3/2024
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-023-07128-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Marked neuropsychiatric involvement and dysmorphic features in nemaline myopathy

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 3/2024

Five-year stroke prognosis. Influence of post-stroke delirium and post-stroke dementia on mortality and disability (Research Study – Part of the PROPOLIS Study)

Sexual dysfunction in a sample of Egyptian patients with Parkinson’s disease

A case of Mills’ syndrome: initially characterized by one cerebral hemisphere atrophy and decreased brain metabolism then evolving into amyotrophic lateral sclerosis

Subarachnoid hemorrhage due to pituitary adenoma apoplexy—case report and review of the literature

Phenotypes and clinical subgroups in vestibular migraine: a cross-sectional study with cluster analysis

The effects of rTMS on motor recovery after stroke: a systematic review of fMRI studies