RESUMO
PURPOSE: Cerebellar hypoplasia and atrophy (CBHA) in children is an extremely heterogeneous group of disorders, but few comprehensive genetic studies have been reported. Comprehensive genetic analysis of CBHA patients may help differentiating atrophy and hypoplasia and potentially improve their prognostic aspects. METHODS: Patients with CBHA in 176 families were genetically examined using exome sequencing. Patients with disease-causing variants were clinically evaluated. RESULTS: Disease-causing variants were identified in 96 of the 176 families (54.5%). After excluding 6 families, 48 patients from 42 families were categorized as having syndromic associations with CBHA, whereas the remaining 51 patients from 48 families had isolated CBHA. In 51 patients, 26 aberrant genes were identified, of which, 20 (76.9%) caused disease in 1 family each. The most prevalent genes were CACNA1A, ITPR1, and KIF1A. Of the 26 aberrant genes, 21 and 1 were functionally annotated to atrophy and hypoplasia, respectively. CBHA+S was more clinically severe than CBHA-S. Notably, ARG1 and FOLR1 variants were identified in 2 families, leading to medical treatments. CONCLUSION: A wide genetic and clinical diversity of CBHA was revealed through exome sequencing in this cohort, which highlights the importance of comprehensive genetic analyses. Furthermore, molecular-based treatment was available for 2 families.
Assuntos
Exoma , Malformações do Sistema Nervoso , Criança , Humanos , Exoma/genética , Mutação , Malformações do Sistema Nervoso/genética , Atrofia/genética , Receptor 1 de Folato/genética , CinesinasRESUMO
We report two patients with latent general myasthenia gravis (MG) with refractory ocular symptoms who were successfully treated with pre-evening meal administration of tacrolimus. Patient 1 was a 4-year-old girl with persistent ocular symptoms despite high-dose steroid therapy and thymectomy. Oral tacrolimus was initiated at the age of 3 years, which was resulted in complete resolution of symptoms. After one year, hemilateral ptosis recurred. The plasma consentration of tacrolimus was very low, probably due to sudden weight gain. Increasing the dose and a change from post- to pre-evening meal administration of tacrolimus enabled maintenance of its concentration and complete control of ocular symptoms. Patient 2 was a 2-year-old boy whose symptoms were refractory to steroid therapy after his first relapse. Since post-meal administration of tacrolimus provided partial benefit, the closing schedule was changed to pre-evening meal administration, with good results. Neither patient had adverse effects of tacrolimus. It is difficult to maintain an effective tacrolimus concentration in children due to marked growth and rapid metabolic rates. Pre-evening meal administration of tacrolimus is an easy, safe and useful method of treatment in MG young children.
Assuntos
Imunossupressores/uso terapêutico , Refeições , Miastenia Gravis/tratamento farmacológico , Refração Ocular/efeitos dos fármacos , Tacrolimo/uso terapêutico , Pré-Escolar , Feminino , Humanos , Masculino , Miastenia Gravis/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Subtelomeric imbalances are a frequent cause of cytogenetic abnormalities in patients with unexplained intellectual disability. Functional disomy of Xq28 involving the methyl-CpG-binding protein 2 gene (MECP2) has been observed mostly in subtelomeric duplications. We identified three patients with functional disomy of Xq28. A female patient showed an unbalanced translocation between 12q24.33 and Xq28. Two male patients showed an unbalanced translocation between Xq27.1- Yq11.22 and a recombinant X-chromosome containing duplicated material from Xq27.1 on Xp telomere, respectively. All three patients exhibited severe developmental delay, hypotonia, seizures, and distinctive facial features, including flat nasal bridge and hypertelorism. Additionally, brain magnetic resonance imaging (MRI) showed characteristic findings in each patient, including frontal dominant brain atrophy and hypoplasia of the corpus callosum, which are common findings in patients with functional disomies of Xq28 and interstitial duplications of Xq28, including MECP2. Brain MRI revealed a cystic lesion in the periventricular white matter in a patient, similar to our previous experience in patients with MECP2 duplication syndrome. Thus, white matter abnormalities may frequently be seen in cases of patients with additional MECP2 copies. © 2013 Wiley Periodicals, Inc.