The Clinical Heterogeneity of Spinal Muscular Atrophy with Respiratory Distress Type 1 (SMARD1)—A Report of Three Cases, Including Twins

Author:

Leśniak Alicja1ORCID,Glińska Marta1ORCID,Patalan Michał1ORCID,Ostrowska Iwona1,Świrska-Sobolewska Monika1,Giżewska-Kacprzak Kaja2,Kotkowiak Agata1,Leśniak Anna1,Walczak Mieczysław1,Śmigiel Robert3ORCID,Giżewska Maria1

Affiliation:

1. Department of Pediatrics, Endocrinology, Diabetology, Metabolic Diseases and Cardiology of the Developmental Age, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland

2. Department of Pediatric and Oncological Surgery, Urology and Hand Surgery, Pomeranian Medical University in Szczecin, Prof. Tadeusz Sokołowski University Clinical Hospital No. 1, 71-252 Szczecin, Poland

3. Department of Pediatrics, Endocrinology, Diabetology and Metabolic Diseases, Wroclaw Medical University, 50-368 Wroclaw, Poland

Abstract

Spinal muscular atrophy with respiratory distress type 1 (SMARD1; OMIM #604320, ORPHA:98920) is a rare autosomal recessive congenital motor neuron disease. It is caused by variants in the IGHMBP2 gene. Clinically, it presents with respiratory failure due to diaphragmatic paralysis, progressive muscle weakness starting in the distal parts of the limbs, dysphagia, and damage to sensory and autonomic nerves. Unlike spinal muscular atrophy (SMA), SMARD1 has a distinct genetic etiology and is not detected in the population newborn screening programs. Most children with SMARD1 do not survive beyond the first year of life due to progressive respiratory failure. Artificial ventilation can prolong survival, but no specific treatment is available. Therapy focuses on mechanical ventilation and improving the patient’s quality of life. Research into gene therapy is ongoing. We report three female patients with SMARD1, including twins from a triplet pregnancy. In twin sisters (patient no. 1 and patient no. 2), two heterozygous variants in the IGHMBP2 gene were identified: c.595G>C/p.Ala199Pro and c.1615_1623del/p.Ser539_Tyr541del. In patient no. 3, a variant c.1478C>T/p.Thr493Ile and a variant c.439C>T/p.Arg147* in the IGHMBP2 gene were detected. Our findings underscore the variability of clinical presentations, even among patients sharing the same pathogenic variants in the IGHMBP2 gene, and emphasize the importance of early genetic diagnosis in patients presenting with respiratory failure, with or without associated diaphragmatic muscle paralysis.

Publisher

MDPI AG

Reference31 articles.

1. The Natural Course of Infantile Spinal Muscular Atrophy with Respiratory Distress Type 1 (SMARD1);Guenther;Pediatrics,2012

2. (2024, April 16). Neuronopathy, Distal Hereditary Motor, Autosomal Recessive 1. Available online: https://www.omim.org/entry/604320.

3. Respiratory distress as the initial manifestation of Werdnig-Hoffmann disease;Mellins;Pediatrics,1974

4. Distal infantile spinal muscular atrophy associated with paralysis of the diaphragm: A variant of infantile spinal muscular atrophy;Bertini;Am. J. Med. Genet.,1989

5. (2024, April 16). Spinal Muscular Atrophy, Type I. Available online: https://www.omim.org/entry/253300.

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