RESUMEN
Siblings of non-consanguineous Jewish-Ethiopian ancestry presented with congenital axial hypotonia, weakness of the abducens nerve, psychomotor developmental delay with brain ventriculomegaly, variable thinning of corpus callosum and cardiac septal defects. Homozygosity mapping identified a single disease-associated locus of 3.5 Mb on chromosome 3. Studies of a Bedouin consanguineous kindred affected with a similar recessive phenotype identified a single disease-associated 18 Mb homozygosity locus encompassing the entire 3.5 Mb locus. Whole exome sequencing demonstrated only two homozygous mutations within a shared identical haplotype of 0.6 Mb, common to both Bedouin and Ethiopian affected individuals, suggesting an ancient common founder. Only one of the mutations segregated as expected in both kindreds and was not found in Bedouin and Jewish-Ethiopian controls: c.1404A>G, p.[*468Trpext*6] in CCDC174. We showed that CCDC174 is ubiquitous, restricted to the cell nucleus and co-localized with EIF4A3. In fact, yeast-two-hybrid assay demonstrated interaction of CCDC174 with EIF4A3, a component of exon junction complex. Knockdown of the CCDC174 ortholog in Xenopus laevis embryos resulted in poor neural fold closure at the neurula stage with later embryonic lethality. Knockdown embryos exhibited a sharp reduction in expression of n-tubulin, a marker for differentiating primary neurons, and of hindbrain markers krox20 and hoxb3. The Xenopus phenotype could be rescued by the human normal, yet not the mutant CCDC174 transcripts. Moreover, overexpression of mutant but not normal CCDC174 in neuroblastoma cells caused rapid apoptosis. In line with the hypotonia phenotype, the CCDC174 mutation caused depletion of RYR1 and marked myopathic changes in skeletal muscle of affected individuals.
Asunto(s)
Exones , Hipotonía Muscular/genética , Mutación , Proteínas/genética , Trastornos Psicomotores/genética , Cromosomas Humanos Par 3 , ARN Helicasas DEAD-box , Factor 4A Eucariótico de Iniciación , Genes Recesivos , Estudios de Asociación Genética , Ligamiento Genético , Haplotipos , Homocigoto , Humanos , Recién Nacido , Masculino , Hipotonía Muscular/congénito , Linaje , Trastornos Psicomotores/congénito , Técnicas del Sistema de Dos HíbridosRESUMEN
Children with severe congenital heart defects (CHD) requiring open heart surgery in the first year of life are at high risk for developing neurological and psychomotor abnormalities. Depending on the type and severity of the CHD, between 15 and over 50% of these children have deficits, which are usually confined to distinct domains of development, although formal intelligence tends to be normal. Children with mild CHD, who comprise the majority of congenital heart defects, have a far better developmental prognosis than those with complex CHD. This review concentrates on the impact of severe CHD on the developing brain of the foetus and infant. It also provides a summary of recent clinical and neuroimaging studies, and an overview of the long-term neurological prognosis. Advanced neuroimaging modalities indicate that, related to altered cerebral blood flow and oxygenation, foetuses with severe CHD show delayed third trimester brain maturation and increased vulnerability for hypoxic injury. Morphological and neurological abnormalities are present before surgery, commonly affecting the white matter. In the long-term, impaired neurological and developmental outcomes are related to the combination of prenatal, perinatal and additional perioperative risk factors. Therefore, new therapeutic approaches aim to optimise the intra- and perinatal management of foetuses and newborns with congenital heart defects. Identification and avoidance of risk factors, early neurodevelopmental assessment and therapy may optimise the long-term outcome in this high-risk population.
Asunto(s)
Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/fisiopatología , Enfermedades del Sistema Nervioso/congénito , Enfermedades del Sistema Nervioso/fisiopatología , Trastornos Psicomotores/congénito , Trastornos Psicomotores/fisiopatología , Niño , Preescolar , Femenino , Cardiopatías Congénitas/epidemiología , Humanos , Lactante , Recién Nacido , Enfermedades del Sistema Nervioso/epidemiología , Prevalencia , Pronóstico , Trastornos Psicomotores/epidemiología , Factores de RiesgoRESUMEN
This report describes a 3-year-old Chinese-Italian boy with Joubert syndrome. Fundus examination showed bilateral optic disc coloboma. Left serous retinal detachment was also found. This ocular finding was not reported in the previous literature. Although Joubert syndrome has many variable phenotypes and the molecular basis is still unknown, the newly reported ocular features suggest that a different genetic form may be present.
Asunto(s)
Ataxia Cerebelosa/complicaciones , Cerebelo/anomalías , Hipotonía Muscular/complicaciones , Trastornos Psicomotores/complicaciones , Desprendimiento de Retina/etiología , Ataxia Cerebelosa/diagnóstico , Preescolar , Diagnóstico Diferencial , Humanos , Imagen por Resonancia Magnética , Masculino , Hipotonía Muscular/congénito , Hipotonía Muscular/diagnóstico , Trastornos Psicomotores/congénito , Trastornos Psicomotores/diagnóstico , Desprendimiento de Retina/diagnóstico , Retinoscopía , SíndromeRESUMEN
Congenital mirror movements (CMMs) are involuntary, symmetric movements of one hand during the production of voluntary movements with the other. CMMs have been attributed to a range of physiological mechanisms, including excessive ipsilateral projections from each motor cortex to distal extremities. We examined this hypothesis with an individual showing pronounced CMMs. Mirror movements were characterized for a set of hand muscles during a simple contraction task. Transcranial magnetic stimulation (TMS) was then used to map the relative input to each muscle from both motor cortices. Contrary to our expectations, CMMs were most prominent for muscles with the strongest contralateral representation rather than in muscles that were activated by stimulation of either hemisphere. These findings support a bilateral control hypothesis whereby CMMs result from the recruitment of both motor cortices during intended unimanual movements. Consistent with this hypothesis, bilateral motor cortex activity was evident during intended unimanual movements in an fMRI study. To assess the level at which bilateral recruitment occurs, motor cortex excitability during imagined unimanual movements was assessed with TMS. Facilitory excitation was only observed in the contralateral motor cortex. Thus, the bilateral recruitment of the hemispheres for unilateral actions in individuals with CMMs appears to occur during movement execution rather than motor planning.
Asunto(s)
Dominancia Cerebral/fisiología , Lateralidad Funcional/fisiología , Imagen por Resonancia Magnética , Corteza Motora/fisiopatología , Músculo Esquelético/inervación , Trastornos Psicomotores/congénito , Tractos Piramidales/fisiopatología , Reclutamiento Neurofisiológico/fisiología , Adulto , Mapeo Encefálico , Electromiografía , Potenciales Evocados Motores/fisiología , Mano/inervación , Humanos , Masculino , Inhibición Neural/fisiología , Trastornos Psicomotores/fisiopatología , Desempeño Psicomotor , Valores de Referencia , Estimulación Magnética TranscranealRESUMEN
Agyria-pachygyria complex is a disorder of neuronal migration and organization. Patients suffer either motor or intellectual retardation. We report our experiences of 10 patients with agyria-pachygyria complex and evaluate their clinical features, electroencephalography, and evoked potentials. Of nine electroencephalography examinations, five patients demonstrated characteristically high-amplitude fast activity. One of nine patients had an abnormal brainstem auditory-evoked potential. Three of seven patients had abnormal goggled visual-evoked potential. Six patients received somatosensory-evoked potential examinations, and five of these were abnormal, including four with prolonged central conduction times. Of the 10 patients, eight survived with variable intellectual and motor retardation; two died of sepsis. Patients with grades 1-4 agyria-pachygyria had high incidences of somatosensory-evoked potential abnormalities and also suffered worse neurologic outcomes. Normal brainstem auditory-evoked potential but abnormal cortical somatosensory-evoked potential components and prolonged central conduction time in these patients indicate that agyria-pachygyria is a supratentorial disease. We conclude that somatosensory-evoked potential examination is supplemental to neuroimaging in predicting the neurologic prognosis of patients with agyria-pachygyria.
Asunto(s)
Encéfalo/anomalías , Electroencefalografía , Imagen por Resonancia Magnética , Adolescente , Encéfalo/patología , Encéfalo/fisiopatología , Niño , Preescolar , Epilepsia Tónico-Clónica/congénito , Epilepsia Tónico-Clónica/diagnóstico , Epilepsia Tónico-Clónica/fisiopatología , Femenino , Humanos , Lactante , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/fisiopatología , Masculino , Conducción Nerviosa/fisiología , Examen Neurológico , Neuronas/fisiología , Pronóstico , Trastornos Psicomotores/congénito , Trastornos Psicomotores/diagnóstico , Trastornos Psicomotores/fisiopatología , Tiempo de Reacción/fisiología , Espasmos Infantiles/congénito , Espasmos Infantiles/diagnóstico , Espasmos Infantiles/fisiopatologíaAsunto(s)
Anomalías Múltiples/metabolismo , Hemangiosarcoma/metabolismo , Proteínas Tirosina Quinasas Receptoras/biosíntesis , Receptores de Factores de Crecimiento/biosíntesis , Neoplasias Cutáneas/metabolismo , Agenesia del Cuerpo Calloso , Coroides/anomalías , Femenino , Hemangiosarcoma/química , Humanos , Lactante , Trastornos Psicomotores/congénito , Receptores de Factores de Crecimiento Endotelial Vascular , Retina/anomalías , Neoplasias Cutáneas/químicaAsunto(s)
Discapacidades del Desarrollo/diagnóstico , Trastornos de la Percepción/diagnóstico , Trastornos Psicomotores/congénito , Trastornos de la Visión/congénito , Percepción Visual , Preescolar , Discapacidades del Desarrollo/fisiopatología , Potenciales Evocados Visuales/fisiología , Humanos , Lactante , Recién Nacido , Imagen por Resonancia Magnética , Trastornos de la Percepción/fisiopatología , Trastornos Psicomotores/diagnóstico , Trastornos Psicomotores/fisiopatología , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/fisiopatología , Vías Visuales/patología , Vías Visuales/fisiopatología , Percepción Visual/fisiologíaRESUMEN
CONTEXT: Rehabilitation for children with congenital hemiplegia to improve function in the impaired upper limb and enhance participation may be time-consuming and costly. OBJECTIVES: To systematically review the efficacy of nonsurgical upper-limb therapeutic interventions for children with congenital hemiplegia. METHODS: The Cochrane Central Register of Controlled Trials, Medline, CINAHL (Cumulative Index to Nursing and Allied Health Literature), AMED (Allied and Complementary Medicine), Embase, PsycINFO, and Web of Science were searched up to July 2008. Data sources were randomized or quasi-randomized trials and systematic reviews. RESULTS: Twelve studies and 7 systematic reviews met our criteria. Trials had strong methodologic quality (Physiotherapy Evidence Database [PEDro] scale > or = 5), and systematic reviews rated strongly (AMSTAR [Assessment of Multiple Systematic Reviews] score > or = 6). Four interventions were identified: intramuscular botulinum toxin A combined with upper-limb training; constraint-induced movement therapy; hand-arm bimanual intensive training; and neurodevelopmental therapy. Data were pooled for upper-limb, self-care, and individualized outcomes. There were small-to-medium treatment effects favoring intramuscular botulinum toxin A and occupational therapy, neurodevelopmental therapy and casting, constraint-induced movement therapy, and hand-arm bimanual intensive training on upper-limb outcomes. There were large treatment effects favoring intramuscular botulinum toxin A and upper-limb training for individualized outcomes. No studies reported participation outcomes. CONCLUSIONS: No one treatment approach seems to be superior; however, injections of botulinum toxin A provide a supplementary benefit to a variety of upper-limb-training approaches. Additional research is needed to justify more-intensive approaches such as constraint-induced movement therapy and hand-arm bimanual intensive training.
Asunto(s)
Toxinas Botulínicas Tipo A/administración & dosificación , Parálisis Cerebral/congénito , Parálisis Cerebral/rehabilitación , Terapia Ocupacional , Modalidades de Fisioterapia , Trastornos Psicomotores/congénito , Trastornos Psicomotores/rehabilitación , Adolescente , Niño , Preescolar , Terapia Combinada , Humanos , Lactante , Ensayos Clínicos Controlados Aleatorios como Asunto , Férulas (Fijadores)Asunto(s)
Discapacidad Intelectual/genética , Enfermedades Renales/genética , Trastornos Psicomotores/genética , Trombocitopenia/genética , Adolescente , Desarrollo del Adolescente , Niño , Desarrollo Infantil , Femenino , Predisposición Genética a la Enfermedad , Herencia , Humanos , Hipertensión/diagnóstico , Hipertensión/genética , Discapacidad Intelectual/diagnóstico , Enfermedades Renales/congénito , Enfermedades Renales/diagnóstico , Masculino , Linaje , Fenotipo , Proteinuria/diagnóstico , Proteinuria/genética , Trastornos Psicomotores/congénito , Trastornos Psicomotores/diagnóstico , Trastornos del Habla/diagnóstico , Trastornos del Habla/genética , Síndrome , Trombocitopenia/congénito , Trombocitopenia/diagnósticoRESUMEN
Congenital nephrotic syndrome (CNS) comprises a heterogeneous group of conditions having in common the disruption of normal glomerular permselectivity, and it carries a poor prognosis, with most patients progressing to end-stage renal disease. Recently, mutations in the LAMB2 gene encoding laminin beta2 were described as the cause of Pierson syndrome, which is characterized by CNS and a complex ocular maldevelopment with microcoria as the most prominent clinical features. Most affected children exhibit early onset of chronic renal failure, neurodevelopmental deficits, and blindness. We report on a patient with CNS, high-grade myopia, and minor structural eye anomalies, including remnants of pupillary membranes, but no microcoria. The patient had not developed renal failure by the age of 16 months, and he showed no neurodevelopmental deficits. He was identified to be homozygous for a novel LAMB2 missense mutation. This observation, together with two recent reports on milder variants of Pierson syndrome, corroborates the concept that the clinical expression of Pierson syndrome is more variable than initially described, and that milder phenotypes may be related to hypomorphic LAMB2 alleles.
Asunto(s)
Anomalías Múltiples/diagnóstico , Laminina/genética , Síndrome Nefrótico/congénito , Síndrome Nefrótico/diagnóstico , Anomalías Múltiples/genética , Anomalías Múltiples/metabolismo , Ceguera/congénito , Ceguera/genética , Anomalías del Ojo/genética , Humanos , Lactante , Laminina/metabolismo , Masculino , Hipotonía Muscular/congénito , Hipotonía Muscular/genética , Mutación Missense , Síndrome Nefrótico/genética , Trastornos Psicomotores/congénito , Trastornos Psicomotores/genética , SíndromeRESUMEN
Norrie disease (ND) is an X-linked disorder, inherited as a recessive trait that, therefore, mostly affects males. The gene responsible for ND, called NDP, maps to the short arm of chromosome X (Xp11.4-p11.3). We report here an atypical case of ND, consisting of a patient harboring a large submicroscopic deletion affecting not only the NDP gene but also the MAOA, MAOB, and EFHC2 genes. Microarray comparative genomic hybridization (CGH) analysis showed that 11 consecutive bacterial artificial chromosome (BAC) clones, mapping around the NDP gene, were deleted. These clones span a region of about 1 Mb on Xp11.3. The deletion was ascertained by fluorescent in situ hybridization (FISH) analysis with different BAC clones located within the region. Clinical features of the proband include bilateral retinal detachment, microcephaly, severe psychomotor retardation without verbal language skills acquired, and epilepsy. The identification and molecular characterization of this case reinforces the idea of a new contiguous gene syndrome that would explain the complex phenotype shared by atypical ND patients.
Asunto(s)
Ceguera/congénito , Proteínas de Unión al Calcio/genética , Epilepsias Mioclónicas/genética , Proteínas del Ojo/genética , Monoaminooxidasa/genética , Proteínas del Tejido Nervioso/genética , Trastornos Psicomotores/genética , Ceguera/genética , Niño , Deleción Cromosómica , Cromosomas Humanos X , Epilepsias Mioclónicas/congénito , Humanos , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Trastornos Psicomotores/congénitoRESUMEN
The suggested link between autism and cerebellar dysfunction formed the background for a Swedish clinical study in 2001. Thirty-two children (17 females, 15 males; mean age 12y, SD 3y 10mo; range 6 to 21y) with a clinical suspicion of non-progressive congenital ataxia were examined, and parents were interviewed about the presence of neuropsychiatric problems in the child. Twelve children had simple ataxia, eight had ataxic diplegia, and 12 had 'borderline' ataxia. All but one of the 32 children had a mild to moderate gross motor disability according to Gross Motor Function Classification System (15 were categorized as level I, 16 as level II, and one child as level IV). Neuroimaging and neuropsychological testing were achieved in most cases. There was a strong association between learning disability* and autism spectrum disorder (often combined with hyperactivity disorder) on the one hand, and both simple and borderline 'ataxia' on the other, but a weaker link between ataxic diplegia and neuropsychiatric disorders. A correlation between cerebellar macropathology on neuroimaging and neuropsychiatric disorders was not supported. Congenital ataxia might not be a clear-cut syndrome of cerebellar disease, but one of many signs of prenatal events or syndromes, leading to a complex neurodevelopmental disorder including autism and learning disability.
Asunto(s)
Ataxia Cerebelosa/congénito , Paraplejía/congénito , Adolescente , Adulto , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Ataxia Cerebelosa/diagnóstico , Ataxia Cerebelosa/fisiopatología , Cerebelo/patología , Cerebelo/fisiopatología , Niño , Comorbilidad , Femenino , Humanos , Discapacidades para el Aprendizaje/diagnóstico , Discapacidades para el Aprendizaje/fisiopatología , Imagen por Resonancia Magnética , Masculino , Examen Neurológico , Pruebas Neuropsicológicas , Paraplejía/diagnóstico , Trastornos Psicomotores/congénito , Trastornos Psicomotores/diagnóstico , Estadística como Asunto , Suecia , Tomografía Computarizada por Rayos XRESUMEN
UNLABELLED: The present case report describes a patient with Klippel-Feil anomaly (KFA) and oligodontia, carrying a de novo pericentric inversion of chromosome 2 (p12q34). KFA is characterised by congenital vertebral fusion of the cervical spine and a wide spectrum of associated anomalies. It therefore constitutes a heterogenous group of clinical conditions and has been classified morphologically, although its aetiology remains unclear. We present an 18-year-old female with KFA, associated with congenital impairment of hearing, psychomotor retardation, speech limitation, short stature, spinal scoliosis, facial asymmetry and latent hypothyroidism. No renal anomaly or heart disease was present. In addition, she exhibited oligodontia of both the deciduous and permanent dentition, a unique characteristic that has not yet been reported in any non-cleft palate KFA case. CONCLUSION: The current report of a patient with oligodontia and an inversion on chromosome 2 may aid in the identification of novel genes for oligodontia.
Asunto(s)
Anodoncia/diagnóstico , Cromosomas Humanos Par 2/genética , Síndrome de Klippel-Feil/diagnóstico , Anomalías Múltiples/diagnóstico , Adolescente , Inversión Cromosómica , Hipotiroidismo Congénito , Asimetría Facial/congénito , Asimetría Facial/diagnóstico , Femenino , Pérdida Auditiva/congénito , Pérdida Auditiva/diagnóstico , Humanos , Hipotiroidismo/diagnóstico , Trastornos Psicomotores/congénito , Trastornos Psicomotores/diagnóstico , Radiografía , Escoliosis/congénito , Escoliosis/diagnóstico , Trastornos del Habla/diagnóstico , Columna Vertebral/diagnóstico por imagenRESUMEN
La displasia septo-óptica o síndrome de De Morsier es un trastornopoco usual del desarrollo embrionario. Consiste en la hipoplasia de uno o ambos nervios ópticos, malformacionescerebrales de la línea media y disfunción hipotálamo-hipofisaria, la cual es inconstante. En el presente trabajo se describen los hallazgos de 9 pacientes con displasia septo-óptica.