Insights into diagnostic difficulties in spinal muscular atrophy: a Case Report series

Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder caused by mutations in SMN1, with disease severity influenced by the number of SMN2 copies. Although SMA is one of the most common autosomal recessive disorders, molecular diagnosis still presents challenges. We present a case ser...

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Main Authors: Kakha Bregvadze, Luka Abashishvili, Nana Nino Tatishvili, Teona Shatirishvili, Ana Bedoshvili, Gocha Chikvinidze, Arndt Rolfs, Volha Skrahina, Tinatin Tkemaladze
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2024.1502444/full
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author Kakha Bregvadze
Luka Abashishvili
Nana Nino Tatishvili
Nana Nino Tatishvili
Teona Shatirishvili
Teona Shatirishvili
Ana Bedoshvili
Ana Bedoshvili
Gocha Chikvinidze
Arndt Rolfs
Arndt Rolfs
Volha Skrahina
Tinatin Tkemaladze
Tinatin Tkemaladze
author_facet Kakha Bregvadze
Luka Abashishvili
Nana Nino Tatishvili
Nana Nino Tatishvili
Teona Shatirishvili
Teona Shatirishvili
Ana Bedoshvili
Ana Bedoshvili
Gocha Chikvinidze
Arndt Rolfs
Arndt Rolfs
Volha Skrahina
Tinatin Tkemaladze
Tinatin Tkemaladze
author_sort Kakha Bregvadze
collection DOAJ
description Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder caused by mutations in SMN1, with disease severity influenced by the number of SMN2 copies. Although SMA is one of the most common autosomal recessive disorders, molecular diagnosis still presents challenges. We present a case series illustrating the variable clinical presentations and diagnostic complexities of spinal muscular atrophy (SMA). Case 1 highlights the importance of multiplex ligation-dependent probe amplification (MLPA) and sequencing for detecting heterozygous deletions and novel variants. Case 2 highlights the limitations of neonatal screening, in which a heterozygous deletion was overlooked. Case 3 demonstrates the need for thorough clinical examination and relevant genetic testing in patients with dual diagnoses, in this case Down syndrome and SMA. In cases 4, 5, and 6, the pseudodominant inheritance pattern is examined in a familial context, highlighting the need for thorough genetic analysis. The presented case series emphasizes the diagnostic challenges and the crucial role of various molecular techniques in the accurate diagnosis and management of SMA.
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institution OA Journals
issn 1664-8021
language English
publishDate 2024-12-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Genetics
spelling doaj-art-24e1825908d8495fad3fd8972f4f40782025-08-20T02:22:10ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-12-011510.3389/fgene.2024.15024441502444Insights into diagnostic difficulties in spinal muscular atrophy: a Case Report seriesKakha Bregvadze0Luka Abashishvili1Nana Nino Tatishvili2Nana Nino Tatishvili3Teona Shatirishvili4Teona Shatirishvili5Ana Bedoshvili6Ana Bedoshvili7Gocha Chikvinidze8Arndt Rolfs9Arndt Rolfs10Volha Skrahina11Tinatin Tkemaladze12Tinatin Tkemaladze13Department of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, GeorgiaDepartment of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, GeorgiaNeuroscience Department, M. Iashvili Children’s Central Hospital, Tbilisi, GeorgiaDepartment of Neurology, David Tvildiani Medical University, Tbilisi, GeorgiaNeuroscience Department, M. Iashvili Children’s Central Hospital, Tbilisi, GeorgiaDepartment of Neurology, David Tvildiani Medical University, Tbilisi, GeorgiaNeuroscience Department, M. Iashvili Children’s Central Hospital, Tbilisi, GeorgiaNeurodevelopment Center, Tbilisi, GeorgiaDepartment of Neurology, I. Tsitsishvili Children’s New Clinic, Tbilisi, GeorgiaMedical Faculty, University of Rostock, Rostock, GermanyRolfs Consulting und Verwaltungs-GmbH (RCV), Berlin, GermanyRolfs Consulting und Verwaltungs-GmbH (RCV), Berlin, GermanyDepartment of Molecular and Medical Genetics, Tbilisi State Medical University, Tbilisi, GeorgiaDepartment of Pediatrics, Givi Zhvania Pediatric Academic Clinic, Tbilisi State Medical University, Tbilisi, GeorgiaSpinal muscular atrophy (SMA) is a progressive neuromuscular disorder caused by mutations in SMN1, with disease severity influenced by the number of SMN2 copies. Although SMA is one of the most common autosomal recessive disorders, molecular diagnosis still presents challenges. We present a case series illustrating the variable clinical presentations and diagnostic complexities of spinal muscular atrophy (SMA). Case 1 highlights the importance of multiplex ligation-dependent probe amplification (MLPA) and sequencing for detecting heterozygous deletions and novel variants. Case 2 highlights the limitations of neonatal screening, in which a heterozygous deletion was overlooked. Case 3 demonstrates the need for thorough clinical examination and relevant genetic testing in patients with dual diagnoses, in this case Down syndrome and SMA. In cases 4, 5, and 6, the pseudodominant inheritance pattern is examined in a familial context, highlighting the need for thorough genetic analysis. The presented case series emphasizes the diagnostic challenges and the crucial role of various molecular techniques in the accurate diagnosis and management of SMA.https://www.frontiersin.org/articles/10.3389/fgene.2024.1502444/fullspinal muscular atrophySMASMN1SMN2Down syndrome
spellingShingle Kakha Bregvadze
Luka Abashishvili
Nana Nino Tatishvili
Nana Nino Tatishvili
Teona Shatirishvili
Teona Shatirishvili
Ana Bedoshvili
Ana Bedoshvili
Gocha Chikvinidze
Arndt Rolfs
Arndt Rolfs
Volha Skrahina
Tinatin Tkemaladze
Tinatin Tkemaladze
Insights into diagnostic difficulties in spinal muscular atrophy: a Case Report series
Frontiers in Genetics
spinal muscular atrophy
SMA
SMN1
SMN2
Down syndrome
title Insights into diagnostic difficulties in spinal muscular atrophy: a Case Report series
title_full Insights into diagnostic difficulties in spinal muscular atrophy: a Case Report series
title_fullStr Insights into diagnostic difficulties in spinal muscular atrophy: a Case Report series
title_full_unstemmed Insights into diagnostic difficulties in spinal muscular atrophy: a Case Report series
title_short Insights into diagnostic difficulties in spinal muscular atrophy: a Case Report series
title_sort insights into diagnostic difficulties in spinal muscular atrophy a case report series
topic spinal muscular atrophy
SMA
SMN1
SMN2
Down syndrome
url https://www.frontiersin.org/articles/10.3389/fgene.2024.1502444/full
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