RESUMO
BACKGROUND AND PURPOSE: Spinal muscular atrophy (SMA) is the most important cause of motor neuron disease in childhood, and continues to represent the leading genetic cause of infant death. Adulthood-onset SMA (SMA type 4) is rare, with few isolated cases reported. The objective of the present study was to describe a cohort of patients with SMA type 4. METHODS: A cross-sectional study was conducted to characterize clinical, genetic, radiological and neurophysiological features of patients with adulthood-onset SMA. Correlation analysis of functional assessment with genetic, radiological and neurophysiological data was performed. RESULTS: Twenty patients with SMA type 4 were identified in a Brazilian cohort of 227 patients with SMA. The most common clinical symptom was limb-girdle muscle weakness, observed in 15 patients (75%). The most frequent neurological findings were absent tendon reflexes in 18 (90%) and fasciculations in nine patients (45%). Sixteen patients (80%) had the homozygous deletion of exon 7 in the SMN1 gene, with 12 patients (60%) showing four copies of the SMN2 gene. The functional scales Hammersmith Functional Motor Scale Expanded, Amyotrophic Lateral Sclerosis Functional Rating Scale Revised, Revised Upper Limb Module and Spinal Muscular Atrophy Functional Rating Scale, as well as the six-minute walk and the Time Up and Go tests showed a correlation with duration of disease. Motor Unit Number Index was correlated both with duration of disease and with performance in functional assessment. Radiological studies exhibited a typical pattern, with involvement of biceps femoris short head and gluteus minimus in all patients. CONCLUSION: This study represents the largest cohort of patients with SMA type 4 and provides functional, genetic, radiological and neurophysiological features that can be used as potential biomarkers for the new specific genetic therapies for SMA.
Assuntos
Atrofia Muscular Espinal , Adulto , Estudos Transversais , Éxons , Homozigoto , Humanos , Lactente , Atrofia Muscular Espinal/diagnóstico por imagem , Atrofia Muscular Espinal/genética , Deleção de SequênciaAssuntos
Leucoencefalopatias/genética , Doença dos Neurônios Motores/genética , Mutação de Sentido Incorreto , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Brasil , Doenças Desmielinizantes/complicações , Doenças Desmielinizantes/diagnóstico , Doenças Desmielinizantes/genética , Humanos , Leucoencefalopatias/complicações , Leucoencefalopatias/diagnóstico , Masculino , Doença dos Neurônios Motores/complicações , Doença dos Neurônios Motores/diagnóstico , Adulto JovemAssuntos
Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/patologia , Mutação de Sentido Incorreto , Transativadores/genética , Idoso , Esclerose Lateral Amiotrófica/diagnóstico , Brasil , Paralisia Bulbar Progressiva/diagnóstico , Paralisia Bulbar Progressiva/etiologia , Paralisia Bulbar Progressiva/genética , Paralisia Bulbar Progressiva/patologia , Progressão da Doença , Humanos , Masculino , Fatores de TempoRESUMO
Leigh syndrome represents a complex inherited neurometabolic and neurodegenerative disorder associated with different clinical, genetic and neuroimaging findings in the context of bilateral symmetrical lesions involving the brainstem and basal ganglia. Heterogeneous neurological manifestations such as spasticity, cerebellar ataxia, dystonia, choreoathetosis and parkinsonism are associated with multisystemic and ophthalmological abnormalities due to >75 different monogenic causes. Here, we describe the clinical and genetic features of a Brazilian cohort of patients with Leigh Syndrome in which muscle biopsy analysis showed mitochondrial DNA defects and determine the utility of whole exome sequencing for a final genetic diagnostic in this cohort.
