Asunto(s)
Lisencefalias Clásicas y Heterotopias Subcorticales en Banda , Humanos , Encéfalo/diagnóstico por imagen , Corteza Cerebral , Lisencefalias Clásicas y Heterotopias Subcorticales en Banda/diagnóstico por imagen , Lisencefalias Clásicas y Heterotopias Subcorticales en Banda/genética , Proteínas del Citoesqueleto/genética , Imagen por Resonancia Magnética , Proteínas Asociadas a Microtúbulos/genética , Mutación , Mutación Missense , Proteínas de Fusión Oncogénica/genéticaRESUMEN
HK1 deficient Haemolytic Anaemia in association with a Neurological Phenotype & co-existing Meckel-Gruber due to CEP290 in a Romani family.
Asunto(s)
Anemia Hemolítica/diagnóstico , Anemia Hemolítica/genética , Antígenos de Neoplasias/genética , Proteínas de Ciclo Celular/genética , Trastornos de la Motilidad Ciliar/diagnóstico , Trastornos de la Motilidad Ciliar/genética , Proteínas del Citoesqueleto/genética , Encefalocele/diagnóstico , Encefalocele/genética , Hexoquinasa/genética , Mutación , Fenotipo , Enfermedades Renales Poliquísticas/diagnóstico , Enfermedades Renales Poliquísticas/genética , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/genética , Alelos , Sustitución de Aminoácidos , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , LinajeRESUMEN
The filamin A gene (FLNA) on Xq28 encodes the filamin A protein. Mutation in FLNA causes a wide spectrum of disease including skeletal dysplasia, neuronal migration abnormality, cardiovascular malformation, intellectual disability and intestinal obstruction. Recently, childhood-onset interstitial lung disease associated with a range of FLNA mutations has been recognised and reported. We document our personal experience of this emerging disorder and compile a comprehensive overview of clinical features and molecular changes in all identifiable published cases. Reviewing the emerging dataset, we underline this unanticipated phenotypic consequence of pathogenic FLNA mutation-associated pulmonary disease.Conclusion: From the emerging data, we suggest that while reviewing complex cases with a sustained oxygen requirement against a clincial background of cardiac concerns or intestinal obstruction to have a high index of suspicion for FLNA related pathology and to instigate early MRI brain scan and FLNA mutation analysis. What is Known: ⢠FLNA gene on Xq28 encodes the filamin A protein and mutation therein is associated with variable phenotypes depending on its nature of mutation. ⢠Loss-of-function mutation of filamin A is associated with X-linked inherited form of periventricular nodular heterotopia with or without epilepsy with most individuals affected being female. There is a recently recognised associated respiratory phenotype. What is New: ⢠The respiratory phenotype in the form of childhood interstitial lung disease is a recently recognised clinical consequence of loss-of-function FLNA mutation. ⢠Rare male patients with loss-of-function FLNA mutation-associated lung disease with residual protein function can survive into infancy with a severe form of the phenotype.
Asunto(s)
Filaminas/genética , Enfermedades Pulmonares Intersticiales/genética , Niño , Preescolar , Femenino , Humanos , Lactante , Pulmón/patología , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/terapia , Imagen por Resonancia Magnética , Masculino , Mutación , Heterotopia Nodular Periventricular/genética , Fenotipo , Tomografía Computarizada por Rayos X , Ultrasonografía Doppler TranscranealAsunto(s)
Sindactilia/genética , Sindactilia/metabolismo , Femenino , Dedos/anomalías , Humanos , Lactante , Síndrome , Dedos del Pie/anomalíasRESUMEN
A 14-year-old boy with relapsed T cell acute lymphoblastic leukaemia received reinduction chemotherapy that included nelarabine, a purine nucleoside analogue known to cause dose-dependent neurotoxicity. Although he achieved aminimal residual disease negative remission after two cycles of chemotherapy he also developed severe, progressive peripheral and central neurotoxicities. Loss of grey-white differentiation was seen on a T2-weighted magnetic resonance imaging brain scan. This unusual clinical picture and previously unreported radiological findings are thought to be due to nelarabine toxicity. He was bridged with 6-mercaptopurine while transplant was deferred pending sustainable neurological improvement. This case posed clinical and ethical dilemmas while demonstrating previously unreported radiological features.
Asunto(s)
Arabinonucleósidos/efectos adversos , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética , Síndromes de Neurotoxicidad/diagnóstico por imagen , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Adolescente , Arabinonucleósidos/administración & dosificación , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células T Precursoras/diagnóstico por imagenRESUMEN
We report recurrence of osteopathia striata with cranial sclerosis (OSCS) in two full siblings conceived by unaffected parents. Molecular confirmation of OSCS in both siblings was achieved by identification of a novel heterozygous mutation in the WTX gene. Neither parent had clinical features of OSCS nor was the pathogenic mutation demonstrable in DNA extracted from both peripheral blood leucocytes and buccal cells. This case demonstrates germline mosaicism in OSCS and represents the third report of mosaicism affecting the germline in families with OSCS. Previous reports were of parental gonadosomal mosaicism, with one showing recurrence in multiple children. Our observation adds to a body of evidence that suggests that germline mosaicism in OSCS may occur more frequently than believed previously and may have implications for counselling families with OSCS.
Asunto(s)
Mutación de Línea Germinal , Mosaicismo , Osteosclerosis/diagnóstico , Osteosclerosis/genética , Hermanos , Proteínas Adaptadoras Transductoras de Señales/genética , Huesos/diagnóstico por imagen , Huesos/patología , Análisis Mutacional de ADN , Femenino , Humanos , Lactante , Imagen por Resonancia Magnética , Mutación , Linaje , Radiografía , Proteínas Supresoras de Tumor/genéticaRESUMEN
We describe the cases of two children who both presented in infancy with recurrent severe pulmonary hypertensive crises. Exhaustive clinical work-up failed to identify an underlying aetiology. The patients had no clinical response to steroids, immunoglobulins, or pulmonary vasodilators. Post-mortem examination revealed extensive invasive pulmonary capillary haemangiomatosis. There was no evidence of pulmonary venous occlusive disease. Given the lethal nature of this condition, early consideration of referral to a lung transplant centre should be considered in selected patients.
Asunto(s)
Capilares , Hemangioma/complicaciones , Hipertensión Pulmonar/etiología , Pulmón/irrigación sanguínea , Neoplasias Vasculares/complicaciones , Resultado Fatal , Femenino , Humanos , Lactante , Recién Nacido , MasculinoRESUMEN
BACKGROUND: PHACE (posterior fossa defects, haemangioma, arterial anomalies, coarctation of the aorta and cardiac defects, eye abnormalities) syndrome describes a constellation of abnormalities that can occur in association with segmental craniofacial infantile haemangioma. OBJECTIVE: To report the spectrum of clinical and imaging abnormalities seen in a cohort of children. MATERIALS AND METHODS: A retrospective review of the clinical and imaging records of all patients diagnosed with PHACE syndrome between 1998 and 2009 was performed. Information sought included patient demographics, craniofacial segments involved, imaging findings and other extracutaneous abnormalities. RESULTS: Twelve patients were diagnosed with PHACE syndrome over 11 years. All patients had a segmental craniofacial haemangioma. Involved facial segments, in order of frequency, were frontotemporal (12), maxillary (8), mandibular (5) and frontonasal (1). The most common extracutaneous abnormalities were neurovascular anomalies (10), with many patients having multiple anomalies. The spectrum of arterial anomalies ranged from hypoplasia (9) to ectasia (3), anomalous origin/course (2) and persistent fetal anastomosis (2). Other anomalies found included cardiac anomalies (3), coarctation of the aorta (2), posterior fossa malformations (1) and sternal region anomalies (1). CONCLUSION: Intracranial anomalies are the most common extracutaneous feature of PHACE syndrome. The contribution of the radiologist in the recognition of such anomalies is important for the diagnosis of PHACE syndrome.
Asunto(s)
Anomalías Múltiples/diagnóstico , Coartación Aórtica/diagnóstico , Fosa Craneal Posterior , Anomalías del Ojo/diagnóstico , Imagen por Resonancia Magnética , Síndromes Neurocutáneos/complicaciones , Coartación Aórtica/patología , Fosa Craneal Posterior/anomalías , Anomalías del Ojo/patología , Femenino , Humanos , Recién Nacido , Masculino , Síndromes Neurocutáneos/diagnóstico , Síndromes Neurocutáneos/patología , Estudios Retrospectivos , SíndromeRESUMEN
A case of central hypoventilation syndrome was identified in a child with brainstem and cervical cord injury following Haemophilus influenzae type b meningitis and extensive herpes simplex infection. This process resulted in a spastic tetraplegia, and the child continues to require respiratory support. Possible mechanisms of causation are discussed including an evolving, progressive inflammatory or vasculitic process in the setting of transient immunosuppression.
Asunto(s)
Haemophilus influenzae tipo b , Herpes Simple/complicaciones , Hipoventilación/microbiología , Hipoventilación/virología , Meningitis por Haemophilus/complicaciones , Preescolar , Humanos , Hipoventilación/patología , Lactante , Infarto/microbiología , Infarto/patología , Infarto/virología , Imagen por Resonancia Magnética , Masculino , Puente/patología , Cuadriplejía/microbiología , Cuadriplejía/patología , Cuadriplejía/virología , Insuficiencia Respiratoria/microbiología , Insuficiencia Respiratoria/patología , Insuficiencia Respiratoria/virología , Médula Espinal/patologíaRESUMEN
Rhombencephalosynapsis is a rare cerebellar malformation that can be associated with anomalies of the cerebral hemispheres and variable degrees of neurodevelopmental delay. A syndromic association, comprising rhombencephalosynapsis, developmental delay, scalp alopecia and trigeminal anaesthesia (Gomez-López-Hernández syndrome) has been described in seven individuals. We report the case of a 2-year-old boy with rhombencephalosynapsis, and review the evidence for a possible diagnosis of Gomez-López-Hernández syndrome. We also discuss other malformations reported in combination with rhombencephalosynapsis, and consider the possibility that a genetic aetiology for syndromic and nonsyndromic forms of rhombencephalosynapsis may be established with more detailed clinical and genetic studies.
Asunto(s)
Anomalías Craneofaciales/patología , Discapacidades del Desarrollo/patología , Hidrocefalia/patología , Rombencéfalo/anomalías , Anomalías Craneofaciales/diagnóstico , Anomalías Craneofaciales/genética , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/genética , Diagnóstico Diferencial , Humanos , Hidrocefalia/diagnóstico , Hidrocefalia/genética , Lactante , Masculino , Rombencéfalo/patología , SíndromeRESUMEN
A distinct form of septo-optic dysplasia (SOD) comprises limb malformations in addition to the characteristic CNS and ocular abnormalities. To date, there have been 4 reports, citing 5 affected patients with this combined phenotype. We now add a further case and present neuroradiological images of the CNS findings in this condition. The striking consistency of the limb malformations and their overlap with the Streeter's band phenotype is emphasized.