Cognitive, communicative, socio-emotional, and adaptive development in children with merosin-deficient muscular dystrophy

Merosin-deficient muscular dystrophy is a neuromuscular disorder with a heterogeneous phenotype caused by deficiency of the extracellular matrix protein laminin-211. Merosinopathy has traditionally been considered primarily a skeletal muscle disease, manifesting with muscular hypotonia, delayed motor development, progressive muscle weakness, contractures, scoliosis, respiratory and nutritional complications. However, accumulating evidence indicates that in merosin-deficient muscular dystrophy the pathological process is not limited to muscle tissue. Involvement of the central nervous system is of particular importance, as it creates pathogenetic prerequisites for impairments in mental development. In the present study, a comprehensive assessment of motor, adaptive, cognitive, communicative, and socioemotional domains was performed using the DP-3 questionnaire in patients with congenital and limbgirdle forms of merosin-deficient muscular dystrophy. The most pronounced decrease in scores was observed in the motor and adaptive domains in patients with the congenital form of the disease; at the same time, some patients demonstrated impairments in the cognitive, communicative, and socio-emotional domains, whereas in individual cases cognitive scores were within or above the average range. These findings highlight the heterogeneity of the cognitive-behavioral profile of the disease and emphasize the need for individualized comprehensive assessment of mental development in patients with merosinopathy.

1. Oliveira J, Gruber A, Cardoso M, et al. LAMA2 gene mutation update: Toward a more comprehensive picture of the laminin-α2 variome and its related phenotypes. Hum Mutat. 2018; 39 (10): 1314–1337.

2. Bouman K, Groothuis JT, Doorduin J, et al. Natural history, outcome measures and trial readiness in LAMA2-related muscular dystrophy and SELENONrelated myopathy in children and adults: protocol of the LAST STRONG study. BMC Neurol. 2021; 21 (1): 313. Published 2021 Aug 12.

3. Jones KJ. The expanding phenotype of laminin alpha2 chain (merosin) abnormalities: case series and review. Journal of Medical Genetics. 2001. № 10 (38). C. 649–657.

4. Løkken N, Born AP, Duno M, Vissing J. LAMA2- related myopathy: Frequency among congenital and limb-girdle muscular dystrophies. Muscle Nerve. 2015; 52 (4): 547–553.

5. Camelo CG, Artilheiro MC, Martins Moreno CA, et al. Brain MRI Abnormalities, Epilepsy and Intellectual Disability in LAMA2 Related Dystrophy – a Genotype/Phenotype Correlation. J Neuromuscul Dis. 2023; 10 (4): 483–492.

6. Oliveira J, Santos R, Soares-Silva I, et al. LAMA2 gene analysis in a cohort of 26 congenital muscular dystrophy patients. Clin Genet. 2008; 74 (6): 502–512.

7. Tan D, Ge L, Fan Y, et al. Natural history and genetic study of LAMA2-related muscular dystrophy in a large Chinese cohort. Orphanet J Rare Dis. 2021; 16 (1): 319. Published 2021 Jul 19.

8. Zambon AA, Ridout D, Main M, et al. LAMA2-related muscular dystrophy: Natural history of a large pediatric cohort. Ann Clin Transl Neurol. 2020; 7 (10): 1870–1882.

9. Oliveira J, Parente Freixo J, Santos M, Coelho T. LAMA2 Muscular Dystrophy. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, eds. GeneReviews®. Seattle (WA): University of Washington, Seattle; June 7, 2012.

10. Natera-de Benito D, Muchart J, Itzep D, et al. Epilepsy in LAMA2-related muscular dystrophy: An electro-clinico-radiological characterization. Epilepsia. 2020; 61 (5): 971–983.

11. Huang X, Tan D, Zhang Z, et al. Unique genotype-phenotype correlations within LAMA2-related limb girdle muscular dystrophy in Chinese patients. Front Neurol. 2023; (14): 1158094. Published 2023 May 3.

12. Salvati A, Bonaventura E, Sesso G, Pasquariello R, et al. Epilepsy in LAMA2-related muscular dystrophy: A systematic review of the literature. Seizure. 2021; (91): 425–436.

13. Radner S, Banos C, Bachay G, et al. β2 and γ3 laminins are critical cortical basement membrane components: ablation of Lamb2 and Lamc3 genes disrupts cortical lamination and produces dysplasia. Dev Neurobiol. 2013; 73 (3): 209–229.

14. Yurchenco PD, McKee KK, Reinhard JR, Rüegg MA. Laminin-deficient muscular dystrophy: Molecular pathogenesis and structural repair strategies. Matrix Biol. 2018; (71–72): 174–187.

15. Alkan A, Sigirci A, Kutlu R, et al. Merosin-negative congenital muscular dystrophy: diffusion-weighted imaging findings of brain. Journal of Child Neurology. 2007; 22 (5): 655–659.

16. Arreguin AJ, Colognato H. Brain Dysfunction in LAMA2-Related Congenital Muscular Dystrophy: Lessons From Human Case Reports and Mouse Models. Frontiers in Molecular Neuroscience. 2020; (13): 118.

17. De Laat ECM, Houwen-van Opstal SLS, Bouman K, et al. A 5-year natural history study in LAMA2-related muscular dystrophy and SELENON-related myopathy: the Extended LAST STRONG study. BMC Neurol. 2024; 24 (1): 409. Published 2024 Oct 23.

18. Enzmann C, Steiner L, Pospieszny K, et al. & Swiss-Reg-NMD Group (2024) A Multicenter Cross-Sectional Study of the Swiss Cohort of LAMA2-Related Muscular Dystrophy. Journal of neuromuscular diseases.

19. Alpern GD. Developmental profile 3 (3rd ed.). 2009.

20. Smirnov II, Popova ES, Serebrovskaya OV, et al. Studying the possibility of using methods for assessing expressive speech developmental disorders in children 3–6 years old. S.S. Korsakov Journal of Neurology and Psychiatry. 2024; 124 (11 vyp 2): 103–109 (in Russ.).

21. Caravale B, Castronovo A, Narducci L, et al. Neurodevelopment in Preterm Children at 12 Months: Aligning Clinical Observations and Parental Insight. 2025. № 9 (12).

22. Yeleswarapu SP WC, Chan YH, et al Outcomes from an enhanced developmental screening programme in Singapore 2025. (202:106220).

23. Papina YuO, Zavadenko NN, Melnik EA, et al. Assessment of social-emotional, cognitive, communicative development and adaptive behavior in children with spinal muscular atrophy 5q. Nervno‑myshechnye bolezni = Neuromuscular Diseases. 2025; 15 (1): 39–52 (in Russ.).

24. Borella LFM, Pereira FV, Mimura PMP, et al. Widening the spectrum of LAMA 2 congenital muscular dystrophy (MDC1A): cobblestone malformation. Arq Neuropsiquiatr. 2022; 80 (3): 333–334.

25. Jayakody H, Zarei S, Nguyen H, et al. Cobblestone Malformation in LAMA2 Congenital Muscular Dystrophy (MDC1A). J Neuropathol Exp Neurol. 2020; 79 (9): 998–1010.

26. Vigliano P, Dassi P, Di Blasi C, et al. LAMA2 stop-codon mutation: merosin-deficient congenital muscular dystrophy with occipital polymicrogyria, epilepsy and psychomotor regression. Eur J Paediatr Neurol. 2009; 13 (1): 72–76.

27. Ahmed M, Marziali LN, Arenas E, et al. French-Constant C. Laminin α2 controls mouse and human stem cell behaviour during midbrain dopaminergic neuron development. 2019. № 16 (146).

28. Morales M, Margolis EB. Ventral tegmental area: cellular heterogeneity, connectivity and behavior. № 2 (18). P. 73–85.

29. Zha J, Yu Y, Cao F, et al. LAMA2 variants associated with muscular dystrophy, brain structural abnormalities, and epilepsy: a genotype-phenotype study. Front Neurol. 2026; (16): 1728652. Published 2026 Jan 6.

30. Ding M, Wang X, Zeng Y, et al. Missense mutations in LAMA2 causing a new phenotype of mild cognitive impairment, proximal myopathy, seizure, and severe leukoencephalopathy: A case report and protein analysis. Clin Neuropathol. 2019; 38 (3): 100–108.