Journal article
Clinical features of collagen VI-related dystrophies: A large Brazilian cohort
Clinical neurology and neurosurgery, Vol.192, pp.105734-105734
05/2020
DOI: 10.1016/j.clineuro.2020.105734
PMID: 32065942
Abstract
•Twenty-eight patients with collagen VI-related dystrophies (COL6-RDs) are presented.•This is the largest cohort of this myopathy in Latin America.•A large clinical variability was seen in this cohort of COL6-RDs.•Ullrich´s phenotype corresponded to 42,8 %; whereas, 25 % had Bethlem´s phenotype.•Homozygous or heterozygous variants were found in COL6A1, COL6A2 and COL6A3.
Collagen VI-related dystrophies (COL6-RDs) have a broad clinical spectrum and are caused by mutations in the COL6A1, COL6A2 and COL6A3 genes. Despite the clinical variability, two phenotypes are classically recognized: Bethlem myopathy (BM, milder form) and Ullrich congenital muscular dystrophy (UCMD, more severe form), with many patients presenting an intermediate phenotype. In this work, we present clinical and genetic data from 28 patients (27 families), aged 6–38 years (mean of 16.96 years), with COL6-RDs.
Clinical, muscle histology and genetic data are presented. COL6A1, COL6A2 and COL6A3 genes were analyzed by next-generation sequencing (NGS).
Homozygous or heterozygous variants were found in COL6A1 (12 families), COL6A2 (12 families) and COL6A3 (3 families). Patients with the severe UCMD phenotype (three cases) had a homogeneous clinical picture characterized by neonatal onset of manifestations, no gait acquisition and a stable course, but with severe respiratory involvement. Most of the patients with the mild UCMD phenotype had neonatal onset of manifestations (88.8 %), delayed motor development (66.6 %), slowly progressive course, pulmonary involvement (55.5 %) and loss of the walking capacity before the age of 10 (66.6 %). In the intermediate group (nine patients), some children had neonatal onset of manifestations (44.5 %) and delayed motor development (88.9 %); but all of them achieved the ability to walk and were still ambulatory. Some patients that had the BM phenotype presented neonatal manifestations (57.1 %); however, all of them had normal motor development and normal pulmonary function. Only one patient from the group of BM lost the walking capacity during the evolution of the disease. Other frequent findings observed in all groups were joint retractions, spinal deformities, distal hyperextensibility, congenital hip dislocation and keloid formation.
COL6-RDs present variable clinical manifestations, but common findings are helpful for the clinical suspicion. NGS is a valuable approach for diagnosis, providing useful information for the genetic counseling of families.
Details
- Title: Subtitle
- Clinical features of collagen VI-related dystrophies: A large Brazilian cohort
- Creators
- Edmar Zanoteli - Universidade de São PauloPriscilla Souza Soares - Universidade de São PauloAndré Macedo Serafim da Silva - Universidade de São PauloClara Gontijo Camelo - Universidade de São PauloAlulin Tácio Quadros Santos Monteiro Fonseca - Universidade de São PauloMarco Antônio Veloso Albuquerque - Universidade de São PauloCristiane Araújo Martins Moreno - Universidade de São PauloOsório Lopes Abath Neto - Universidade de São PauloGil Monteiro Novo Filho - Universidade de São PauloLeslie Domenici Kulikowski - Universidade de São PauloUmbertina Conti Reed - Universidade de São Paulo
- Resource Type
- Journal article
- Publication Details
- Clinical neurology and neurosurgery, Vol.192, pp.105734-105734
- Publisher
- Elsevier B.V
- DOI
- 10.1016/j.clineuro.2020.105734
- PMID
- 32065942
- ISSN
- 0303-8467
- eISSN
- 1872-6968
- Grant note
- DOI: 10.13039/501100001807, name: São Paulo Research Foundation, award: #2014/19285-8
- Language
- English
- Date published
- 05/2020
- Academic Unit
- Pathology
- Record Identifier
- 9984276453402771
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