Hypomyelinating leukodystrophies in adults: Clinical and genetic features.
Eur J Neurol
; 28(3): 934-944, 2021 03.
Article
en En
| MEDLINE
| ID: mdl-33190326
ABSTRACT
BACKGROUND AND PURPOSE:
Little is known about hypomyelinating leukodystrophies (HLDs) in adults. The aim of this study was to investigate HLD occurrence, clinical features, and etiology among undefined leukoencephalopathies in adulthood.METHODS:
We recruited the patients with cerebral hypomyelinating magnetic resonance imaging pattern (mild T2 hyperintensity with normal or near-normal T1 signal) from our cohort of 62 adult index cases with undefined leukoencephalopathies, reviewed their clinical features, and used a leukoencephalopathy-targeted next generation sequencing panel.RESULTS:
We identified 25/62 patients (~40%) with hypomyelination. Cardinal manifestations were spastic gait and varying degree of cognitive impairment. Etiology was determined in 44% (definite, 10/25; likely, 1/25). Specifically, we found pathogenic variants in the POLR3A (n = 2), POLR1C (n = 1), RARS1 (n = 1), and TUBB4A (n = 1) genes, which are typically associated with severe early-onset HLDs, and in the GJA1 gene (n = 1), which is associated with oculodentodigital dysplasia. Duplication of a large chromosome X region encompassing PLP1 and a pathogenic GJC2 variant were found in two patients, both females, with early-onset HLDs persisting into adulthood. Finally, we found likely pathogenic variants in PEX3 (n = 1) and PEX13 (n = 1) and potentially relevant variants of unknown significance in TBCD (n = 1), which are genes associated with severe, early-onset diseases with central hypomyelination/dysmyelination.CONCLUSIONS:
A hypomyelinating pattern characterizes a relevant number of undefined leukoencephalopathies in adulthood. A comprehensive genetic screening allows definite diagnosis in about half of patients, and demonstrates the involvement of many disease-causing genes, including genes associated with severe early-onset HLDs, and genes causing peroxisome biogenesis disorders.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Enfermedades Desmielinizantes
/
Leucoencefalopatías
Límite:
Adult
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Female
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Humans
Idioma:
En
Revista:
Eur J Neurol
Asunto de la revista:
NEUROLOGIA
Año:
2021
Tipo del documento:
Article
País de afiliación:
Italia