RESUMO
The X-linked alpha thalassemia mental retardation (ATR-X) syndrome is a genetic disorder caused by X-linked recessive mutations in ATRX gene, related to a wide spectrum of clinical manifestations, such as alpha thalassemia, developmental delay, genital abnormalities, and gastrointestinal disorders. Patients with ATR-X syndrome can suffer from different types of epileptic seizures, but a severe epileptic encephalopathy pattern has not been described to date. We describe, for the first time, two brothers with genetically confirmed ATR-X syndrome who presented with drug-resistant epileptic encephalopathy, with tonic and polimorphic seizures reported in the elder brother and epileptic spasms in the younger brother. Moreover, both brothers showed a peculiar movement disorder with myoclonus-dystonia, worsened during periods of distress or pain. These cases expand the clinical spectrum of ATR-X syndrome and open new opportunities for the molecular diagnosis of ATRX mutations in male patients with severe epileptic encephalopathies and movement disorders.
Assuntos
Distúrbios Distônicos/diagnóstico , Epilepsias Mioclônicas/diagnóstico , Deficiência Intelectual Ligada ao Cromossomo X/diagnóstico , Puberdade Precoce/diagnóstico , Proteína Nuclear Ligada ao X/genética , Talassemia alfa/diagnóstico , Criança , Distúrbios Distônicos/complicações , Distúrbios Distônicos/genética , Epilepsias Mioclônicas/complicações , Epilepsias Mioclônicas/genética , Humanos , Masculino , Deficiência Intelectual Ligada ao Cromossomo X/complicações , Deficiência Intelectual Ligada ao Cromossomo X/genética , Mutação , Puberdade Precoce/complicações , Puberdade Precoce/genética , Irmãos , Talassemia alfa/complicações , Talassemia alfa/genéticaRESUMO
We describe a 19-month-old male presenting with right stenotic megaureter, anemia and thrombocytopenia, cardiac and ophthalmologic abnormalities. Analysis with array-based comparative genomic hybridization (aCGH) revealed an interstitial deletion of about 2.4 Mb of chromosome 11q24.2q24.3. We compared the phenotype of our patient with that of recently reported patients studied by aCGH, who showed an overlapping deletion. We also analysed the gene content of the deleted region in order to investigate the possible involvement of specific genes in the clinical phenotype.
Assuntos
Síndrome da Deleção Distal 11q de Jacobsen/diagnóstico , Deleção Cromossômica , Cromossomos Humanos Par 11/genética , Hibridização Genômica Comparativa , Genótipo , Humanos , Lactente , Síndrome da Deleção Distal 11q de Jacobsen/genética , Masculino , FenótipoRESUMO
Tuberous sclerosis complex is a genetic, multisystemic disorder characterized by circumscribed benign lesions (hamartomas) in several organs, including brain. This is the result of defects in the TSC1 and/or TSC2 tumor suppressor genes, encoding the hamartin-tuberin complex that inhibits the mammalian target of rapamycin pathway. Specific inhibitors of this pathway have been shown to reduce the volume of subependymal giant cell astrocytomas associated with tuberous sclerosis. Congenital lymphedema is rarely seen in association with tuberous sclerosis, with only a few reported cases. Although this association can be coincidental, the dysgenetic lymphatic system can represent a hamartia as a consequence of gene mutation. We describe a child with congenital lymphedema in tuberous sclerosis and associated subependymal giant cell astrocytoma who experienced lymphangitis under treatment with mammalian target of rapamycin inhibitors. Because our patient did not show worsening of lymphedema, congenital lymphedema does not seem to be a contraindication for this therapy.
