Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two unrelated children with congenital central hypoventilation syndrome (CCHS-Ondine syndrome) and long segment Hirschsprung disease are reported. Patient 1, a girl, is still alive at 3 years. Patient 2, a boy, died of viral pneumonia at 5.5 years. Continuous mechanical ventilation was necessary for months and those children could never be weaned from the respirator during sleep. Seventeen cases of this complex neurocristopathy are reviewed. Only six children (including our cases) survived beyond 2 years of age. Hypotonia, delay in developmental milestones or epilepsy were frequently observed. Ventilator dependency does not improve with time. Multifocal congenital neuroblastoma occurred in two children. Aetiology is unknown.
 ...
PMID:Ondine-Hirschsprung syndrome (Haddad syndrome). Further delineation in two cases and review of the literature. 844 12

We report on a male infant with the rare combined occurrence of congenital central hypoventilation syndrome (CCHS or Ondine's curse), Hirschsprung's disease (HD), and neuroblastoma. Current therapeutical options leave no doubt that children with isolated forms of CCHS, HD, or neuroblastoma must be treated, but management decisions and the ethical dilemma become more difficult with the presence of multiple neurocristopathies. Our patient was dependent on mechanical ventilation and total parenteral nutrition, when a neuroblastoma was diagnosed at age 5 months. We initiated an attempt at curative chemotherapy. The tumor failed to respond to recommended chemotherapeutic regimens, and the patient died at 11 months of age. We emphasize the importance of screening CCHS patients for associated illnesses such as neuroblastoma and ganglioneuroblastoma at time of diagnosis.
 ...
PMID:Congenital central hypoventilation syndrome associated with Hirschsprung's disease and neuroblastoma: case of multiple neurocristopathies. 1174 63

The Phox2b gene is necessary for autonomic nervous-system development. Phox2b-/- mice die in utero with absent autonomic nervous system circuits, since autonomic nervous system neurons either fail to form or degenerate. We first identified the Phox2b human ortholog, PHOX2B, as the gene underlying congenital central hypoventilation syndrome (CCHS, or Ondine curse), with an autosomal dominant mode of inheritance and de novo mutation at the first generation. We have subsequently shown that heterozygous mutations of PHOX2B may account for several combined or isolated disorders of autonomic nervous-system development--namely, tumors of the sympathetic nervous system (TSNS), such as neuroblastoma and late-onset central hypoventilation syndrome. Here, we report the clinical and molecular assessments of a cohort of 188 probands with CCHS, either isolated or associated with Hirschsprung disease and/or TSNS. The mutation-detection rate was 92.6% (174/188) in our series, and the most prevalent mutation was an in-frame duplication leading to an expansion of +5 to +13 alanines in the 20-alanine stretch at the carboxy terminal of the protein. Such findings suggest PHOX2B mutation screening as a simple and reliable tool for the diagnosis of CCHS, independent of the clinically variable phenotype. In addition, somatic mosaicism was detected in 4.5% of parents. Most interestingly, analysis of genotype-phenotype interactions strongly supports the contention that patients with CCHS who develop malignant TSNS will harbor either a missense or a frameshift heterozygous mutation of the PHOX2B gene. These data further highlight the link between congenital malformations and tumor predisposition when a master gene in development is mutated.
 ...
PMID:PHOX2B genotype allows for prediction of tumor risk in congenital central hypoventilation syndrome. 1565 73

The TLX2 (HOX11L1, Ncx, Enx) and PHOX2B genes encode transcription factors crucial in the development of neural-crest-derived cells, leading to ANS (autonomic nervous system) specific neuronal lineages. Moreover, they share a similar expression pattern and are both involved in downstream steps of BMP (bone morphogenetic protein) signalling. In an attempt to reconstruct the gene network sustaining the correct development of the ANS, we have undertaken an in vitro experimental strategy to identify direct upstream regulators of the TLX2 gene. After characterizing a sequence displaying enhancer property in its 5' flanking region, we confirmed the functional link between the human PHOX2B and TLX2 genes. Transient transfections and electrophoretic-mobility-shift assays suggested that PHOX2B is able to bind the cell-specific element in the 5' regulatory region of the TLX2 gene, determining its transactivation in neuroblastoma cells. Such interaction was also confirmed in vivo by means of chromatin immunoprecipitation assay and, in addition, up-regulation of endogenous TLX2 mRNA level was demonstrated following PHOX2B over-expression, by quantitative real-time PCR. Finally, PHOX2B proteins carrying mutations responsible for CCHS (congenital central hypoventilation syndrome) development showed a severe impairment in activating TLX2 expression, both in vitro and in vivo. Taken together, these results support the PHOX2B-TLX2 promoter interaction, suggesting a physiological role in the transcription-factor cascade underlying the differentiation of neuronal lineages of the ANS during human embryogenesis.
 ...
PMID:The TLX2 homeobox gene is a transcriptional target of PHOX2B in neural-crest-derived cells. 1640 14

Sleep disorders are classified in dyssomnias, parasomnias, sleep disorder associated with medical and psychiatric disorders and proposed sleep disorders. Only the parasomnias have been studied as such in the newborn period. The parasomnias that occur in this age group are infant sleep apnea, congenital central hypoventilation syndrome, sudden infant death syndrome, and benign neonatal sleep myoclonus. Infant sleep apnea includes three entities: (1) apnea of prematurity, (2), apparent life threatening episodes with apnea and (3) obstructive sleep apnea. Congenital central hypoventilation syndrome can be associated with other autonomic system illness, such as Hirschsprung disease (Haddad syndrome) and neuroblastoma. The implementation of the supine sleep position and smoking free homes has diminished the frequency of sudden infant death syndrome. Benign neonatal sleep myoclonus should be considered in all newborns with a normal exam between the episodes when they always occur during sleep. This entity may be mistaken for status epilepticus, because it is associated with increases in heart rate. Benzodiazepines prolongs the duration of the episodes.
 ...
PMID:[Sleep disorders in the newborn]. 1842 81