Natural history of spinal muscular atrophy in children: an analysis of 117 cases / 中国当代儿科杂志

OBJECTIVES@#To study the natural history of spinal muscular atrophy (SMA) in Chongqing and surrounding areas, China, and to provide a clinical basis for comprehensive management and gene modification therapy for SMA.@*METHODS@#A retrospective analysis was performed on the medical data and survival status of 117 children with SMA.@*RESULTS@#Of the 117 children, 62 (53.0%) had type 1 SMA, 45 (38.5%) had type 2 SMA, and 10 (8.5%) had type 3 SMA, with a median age of onset of 2 months, 10 months, and 15 months, respectively. Compared with the children with type 2 SMA or type 3 SMA, the children with type 1 SMA had significantly shorter time to onset, consultation, and confirmed diagnosis (@*CONCLUSIONS@#There are differences in clinical manifestations and survival rates among children with different types of SMA. The children with type 1 SMA have a low survival rate, and those with type 2 SMA may have non-linear regression of motor ability. Early identification and management of SMA should be performed in clinical practice.

Atrofia muscular espinal en el niño / Spinal muscular atrophy present in children

Las atrofias musculares espinales en la infancia (AME) son trastornos genéticos autosómicos recesivos, caracterizados por degeneración de las motoneuronas espinales y bulbares. El presente estudio tuvo el objetivo principal de describir las principales características clínicas en una serie de niños con AME. MÉTODOS. Se realizó un estudio retrospectivo de los pacientes con AME atendidos en el Instituto de Neurología y Neurocirugía de Cuba, entre enero de 1997 y diciembre de 2001. Se recopilaron los datos de 35 pacientes, 4 de ellos, fetos con confirmación prenatal de AME. Se precisaron las principales características clínicas, electromiográficas, de la biopsia muscular y de los estudios genéticos moleculares realizados en cada caso. RESULTADOS. La AME de tipo II resultó la forma clínica mas frecuente (58 por ciento), seguida por la AME de tipo I (42 por ciento). Las principales manifestaciones clínicas resultaron la debilidad muscular generalizada con predominio proximal en extremidades, asociada a hipotonía y arreflexia osteotendinosa. La deleción de los exones 7 y 8 del gen SMN1 se detectó en 20 de 23 casos estudiados (87 por ciento).

Spinal muscular atrophies (SMA) in childhood are autosomal recessive genetic disorders, characterized by spinal and bulbar motoneurons degenerations. Aim of present paper was to describe the main clinical features in a series of children presenting SMA. METHODS: A retrospective study of patients with SMA seen in the Neurology and Neurosurgery Institute of Cuba from January, 2997 and December, 2001 was made. Data from 35 patients were available; four of them were fetus with prenatal confirmation of SMA. Main clinical, electromyography, muscular biopsy, and of molecular genetic studies performed in each case were determined. RESULTS: Type II SMA was the more frequent clinical presentation (58 percent), followed by type I SMA (42, percent). Main clinical manifestations were a systemic muscular weakness with predominance of the proximal type in limbs, associated to hypoxia and osteotendinous areflexia. Seven and eight exons deletion SMN1 gen was detected in 20 from 23 study cases (87 percent).

[Clinical, electrophysiologic and genetic characteristics of childhood onset spinal muscular atrophy]

Spinal muscular atrophy[SMA] is one of the most common autosomal recessive disorders characterized by degeneration of anterior born cells in the spinal cords and leads to progressive muscular weakness and atrophy. The last 10 years have seen major advances in the field of diagnosis of SMA, but no curative treatment is available now. This study aimed to analyze the clinical characteristics of different types of SMA, improve the clinical diagnosis of SMA and prenatal diagnosis of SMA by gene analysis. Patients with SMA were recruited from neurologic clinic from January 2004 to March 2006. The diagnosis of SMA was made from clinical history and examination, electro physiologic assessment or molecular studies. The clinical characteristics and changes of electrophysiology were assessed in all patients. The deletion of survival motor neuron [SMN] and neuronal apoptosis inhibitory protein [NAIP] genes was studied by PCR. Based on age of onset, age of death, achievement of motor milestones and ambulatory status patients classified into SMA I, SMA II and SMA III. The 42 patients, including 28[66.7%] males and 14[33.3%] females were enrolled in this study. The patients were subdivided into clinical groups: 30 [71.7%] of case with SMA I 9[21.4%] of cases with SMA II, 2[4.8%] of case with SMA III and 1[2.4%] of cases with SMA diaphragmatic. They were all characterized by symmetric muscle weakness [more proximal than distal] associated with atrophy, absence or marked decrease of deep tendon reflexes. Fasciculation of tongue was noted in 59.5% of patients. Electroghsiologic studies showed a neurogenic pattern with denervation potentials on 92.8% of cases. The SMN gene was deleted in 78.5% of patients and the NAIP gene was deleted in 54.8% of cases. Deletion of NAIP gene was more common in SMA I, and its deletion correlated with the severity of diseases [P=0.011]. The definite diagnosis of SMA will relay on typical clinical characteristics and changes of electrophysiologic study and gene deletion gene. Genetic diagnosis of SMA can provide a basis of prenatal diagnosis of SMA

Kennedy's disease phenotype with positive genetic study for Kugelberg-Welander's disease: case report

Descrevemos um paciente com achados clínicos de doença de Kennedy e estudo genético positivo para doença de Kugelberg-Welander. Homem, 24 anos e história familiar negativa, iniciou aos 14 anos com atrofia muscular espinhal de caráter progressivo com ginecomastia. Obteve diagnóstico clínico de doença de Kennedy, entretanto o estudo genético foi negativo para esta doença e positivo para doença de Kugelberg-Welander, com deleções dos exons 7 e 8 e do gene do survival of motor neuron.

Diagnosis and screening of spinal-muscular atrophy type III disease through PCR-RFLP in East Azarbaijan during 2004-2005

Hereditary pattern of spinal-muscular atrophy [SMA] disease is in form of recessive autosome with a frequency of 1 in 10000 live births. In most of the patients SMN1 gene bears deletions in exons 7 or 8. The aim of this study is to investigate deletion of above mentioned gene through molecular techniques in east Azarbaigan during 2004-2005. The patients likely to have SMA type III were referred to molecular study following the clinical and laboratory diagnosis. After extraction of DNA from patients' blood the extent of deletion in exons 7 and 8 of SMN1 gene, was investigated through PCR-Restriction Fragment Length Polymorphism [RFLP]. Out of 45 patients likely to have SMA type III, 9 people [20%] had exon deletion in SMN1 gene among whom one patient bore deletion only in exon 7 while the rest bore deletion in both exons [7, 8] of SMN1 gene. Deletion in SMN1 gene was observed in a low percent of the patients likely to have SMA type III. More research including the other sequences of SMN1 gene is recommended