Congenital myasthenic syndrome: Correlation between clinical features and molecular diagnosis
| Autor: | Paulo Victor Partezani Helito, A A Zambon, Umbertina Conti Reed, Hanns Lochmüller, Rachel Thompson, Cristiane de Araújo Martins Moreno, Maria da Penha Morita, Danny Jomaa, Carlos Otto Heise, André Macedo Serafim da Silva, Eduardo de Paula Estephan, João Aris Kouyoumdjian, K. Polavarapu, Edmar Zanoteli, Ana Töpf |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Biopsy Group A Group B Cohort Studies 03 medical and health sciences 0302 clinical medicine health services administration Internal medicine COLQ medicine CHRNE Humans NAV1.4 Voltage-Gated Sodium Channel Muscle Skeletal health care economics and organizations 030304 developmental biology Myasthenic Syndromes Congenital 0303 health sciences biology medicine.diagnostic_test business.industry Congenital myasthenic syndrome medicine.disease 3. Good health RAPSN Phenotype Neurology Cohort Mutation biology.protein Neurology (clinical) business 030217 neurology & neurosurgery |
| Zdroj: | European journal of neurologyREFERENCES. 29(3) |
| ISSN: | 1468-1331 |
| Popis: | Objectives To present phenotype features of a large cohort of congenital myasthenic syndromes (CMS) and correlate them with their molecular diagnosis. Methods Suspected CMS patients were divided into three groups: group A (limb, bulbar or axial weakness, with or without ocular impairment, and all the following: clinical fatigability, electrophysiology compatible with neuromuscular junction involvement and anticholinesterase agents response), group B (limb, bulbar or axial weakness, with or without ocular impairment, and at least one of additional characteristics noted in group A) and group C (pure ocular syndrome). Individual clinical findings and the clinical groups were compared between the group with a confirmed molecular diagnosis of CMS and the group without molecular diagnosis or with a non-CMS molecular diagnosis. Results Seventy-nine patients (68 families) were included in the cohort: 48 in group A, 23 in group B and 8 in group C. Fifty-one were considered confirmed CMS (30 CHRNE, 5 RAPSN, 4 COL13A1, 3 DOK7, 3 COLQ, 2 GFPT1, 1 CHAT, 1 SCN4A, 1 GMPPB, 1 CHRNA1), 7 probable CMS, 5 non-CMS and 16 unsolved. The chance of a confirmed molecular diagnosis of CMS was significantly higher for group A and lower for group C. Some individual clinical features, alterations on biopsy and electrophysiology enhanced specificity for CMS. Muscle imaging showed at least mild alterations in the majority of confirmed cases, with preferential involvement of soleus, especially in CHRNE CMS. Conclusions Stricter clinical criteria increase the chance of confirming a CMS diagnosis, but may lose sensitivity, especially for some specific genes. |
| Databáze: | OpenAIRE |
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