RESUMO
CASK is a multi-domain scaffolding protein that interacts with the transcription factor TBR1 and regulates expression of genes involved in cortical development such as RELN. Here we describe a previously unreported X-linked brain malformation syndrome caused by mutations of CASK. All five affected individuals with CASK mutations had congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia, and severe mental retardation.
Assuntos
Tronco Encefálico/anormalidades , Cerebelo/anormalidades , Doenças Genéticas Ligadas ao Cromossomo X/genética , Guanilato Quinases/genética , Microcefalia/genética , Mutação , Pré-Escolar , Orelha/anormalidades , Feminino , Humanos , Masculino , Deficiência Intelectual Ligada ao Cromossomo X/genética , Proteína Reelina , SíndromeRESUMO
Neurocutaneous melanosis (NM) coexisting with the Dandy-Walker complex (DWC) is a rare condition, with fewer than 15 cases reported in the literature. The authors present a case of an infant with NM and DWC suffering from progressive brainstem compression following ventriculoperitoneal (VP) shunt placement for hydrocephalus. This 1-year-old boy with congenital melanocytic nevi had met normal developmental milestones until the age of 11 months, when he began regressing in ambulation and language function. Intractable vomiting had developed 1 week later. Magnetic resonance (MR) imaging of the brain revealed DWC with hydrocephalus, and spinal MR images demonstrated a proliferative process within the meninges, consistent with NM. The patient underwent right frontal VP shunt placement resulting in immediate symptom relief, but 3 weeks later became irritable, increasingly lethargic, unable to pull to stand, and unable to tolerate solid food without choking. Due to these symptoms and intractable vomiting, the patient presented to the authors' institution. Brain MR imaging revealed a new-onset diffuse cystic process with anterior and posterior brainstem compression, marked kinking of the cervicomedullary junction, melanocyte pigmentation of the left temporal lobe, diffuse leptomeningeal enhancement, and no evidence of hydrocephalus. Consistent with these imaging findings, the degree of brainstem involvement upon gross visualization predictably deterred resection attempts beyond those necessary for biopsy. Pathological examination revealed diffuse melanocytosis, and the family decided not to pursue aggressive measures postoperatively. This report indicates the potential for rapid intracranial manifestation of diffuse melanocytosis in NM patients. Although the prognosis is poor, early neurosurgical involvement in these patients may provide tissue diagnosis and the potential for decompression if the process is caught early in its course.
Assuntos
Tronco Encefálico/patologia , Síndrome de Dandy-Walker/patologia , Hidrocefalia/complicações , Hidrocefalia/cirurgia , Melanose/patologia , Síndromes de Compressão Nervosa/etiologia , Síndromes de Compressão Nervosa/patologia , Síndromes Neurocutâneas/patologia , Complicações Pós-Operatórias/patologia , Derivação Ventriculoperitoneal/efeitos adversos , Síndrome de Dandy-Walker/complicações , Humanos , Lactente , Laminectomia , Imageamento por Ressonância Magnética , Masculino , Melanose/complicações , Melanose/cirurgia , Síndromes Neurocutâneas/complicações , Síndromes Neurocutâneas/cirurgia , Procedimentos Neurocirúrgicos , PrognósticoAssuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Infecções por Enterovirus/prevenção & controle , Hospedeiro Imunocomprometido , Meningite Viral/prevenção & controle , Pneumonia Viral/prevenção & controle , Adolescente , Pré-Escolar , Infecções por Enterovirus/imunologia , Evolução Fatal , Feminino , Humanos , Lactente , Masculino , Meningite Viral/imunologia , Meningite Viral/microbiologia , Pneumonia Viral/imunologia , Pneumonia Viral/microbiologiaRESUMO
Cerebral X-linked adrenoleukodystrophy (X-ALD) is a disorder of very-long-chain fatty acid metabolism, adrenal insufficiency, and cerebral demyelination. Death occurs within 2 to 5 years of clinical onset without hematopoietic cell transplantation (HCT). One hundred twenty-six boys with X-ALD received HCT from 1982 to 1999. Survival, engraftment, and acute graft-versus-host disease were studied. Degree of disability associated with neurologic and neuropsychological function and cerebral demyelination were evaluated before and after HCT. Complete data were available and analyzed for 94 boys with cerebral X-ALD. The estimated 5- and 8-year survival was 56%. The leading cause of death was disease progression. Donor-derived engraftment occurred in 86% of patients. Demyelination involved parietal-occipital lobes in 90%, leading to visual and auditory processing deficits in many boys. Overall 5-year survival of 92% in patients with 0 or 1 neurologic deficits and magnetic resonance imaging (MRI) severity score less than 9 before HCT was superior to survival for all others (45%; P <.01). Baseline neurologic and neuropsychological function, degree of disability, and neuroradiologic status predicted outcomes following HCT. In this first comprehensive report of the international HCT experience for X-ALD, we conclude that boys with early-stage disease benefit from HCT, whereas boys with advanced disease may be candidates for experimental therapies.