Pediatric Autonomic Disorders

Axelrod, Felicia B.; Chelimsky, Gisela; Weese‐Mayer, Debra E.

doi:10.1542/peds.2005-3032

Cited by 110 publications

(69 citation statements)

References 104 publications

(103 reference statements)

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“…Cardiac arrhythmias, such as heart block and Wolff-Parkinson-White syndrome, have been found more predominantly in mtDNA disorders [127]. Autonomic dysfunction may be the cause of bradycardia or tachycardia, and may be diagnosed as postural orthostatic tachycardia syndrome [135,136].…”

Section: Heartmentioning

confidence: 99%

Mitochondrial Disease in Childhood: Nuclear Encoded

2013

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Primary mitochondrial disorders are clinically and genetically heterogeneous, caused by an alteration(s) in either mitochondrial DNA or nuclear DNA, and affect the respiratory chain's ability to undergo oxidative phosphorylation, leading to decreased production of adenosine triphosphophate and subsequent energy failure. These disorders may present at any age, but children tend to have an acute onset of disease compared with subacute or slowly progressive presentation in adults. Varying organ involvement also contributes to the phenotypic spectrum seen in these disorders. The childhood presentation of primary mitochondrial disease is mainly due to nuclear DNA mutations, with mitochondrial DNA mutations being less frequent in childhood and more prominent in adulthood disease. The clinician should be aware of the pediatric presentation of mitochondrial disease and have an understanding of the myriad of nuclear genes responsible for these disorders. The nuclear genes can be best understood by utilizing a classification system of location and function within the mitochondria.

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Section: Heartmentioning

confidence: 99%

Mitochondrial Disease in Childhood: Nuclear Encoded

2013

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“…1 Individuals with CCHS typically present in the newborn period with alveolar hypoventilation during sleep (though more severely affected cases hypoventilate in sleep and wakefulness), an attenuated or absent response to hypoxemia and hypercarbia, evidence of diffuse autonomic dysfunction/dysregulation, 2 and a characteristic facies. 3 More recently, presentation of CCHS in adulthood has also been identified.…”

Section: Congenital Central Hypoventilation Syndrome (Cchs)mentioning

confidence: 99%

Congenital central hypoventilation syndrome: PHOX2B genotype determines risk for sudden death

Gronli

Santucci

Leurgans

et al. 2007

Pediatric Pulmonology

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105

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Summary. Objective: Children with Congenital Central Hypoventilation Syndrome (CCHS) have cardiovascular symptoms consistent with the autonomic nervous system dysregulation/ dysfunction (ANSD) phenotype. We hypothesized that children with CCHS would have a relationship between PHOX2B genotype and two clinically applicable cardiovascular measures of ANSD: duration of longest r-r interval and longest corrected QT interval (QTc). Materials and Methods: We studied 501 days of Holter recordings from 39 individuals with PHOX2B mutationconfirmed CCHS, and analyzed longest r-r and QTc intervals with respect to PHOX2B genotype. Results: We determined that longest r-r interval varied by genotype (P ¼ 0.001), with a positive correlation between repeat number and longest r-r interval duration (P ¼ 0.0007). Number of children with a longest r-r interval value !3 sec varied by genotype (P < 0.0001): 0% with the 20/25 genotype, 19% with the 20/26 genotype, and 83% with the 20/27 genotype. Though longest QTc interval did not vary by genotype (P ¼ 0.09), all children with CCHS had at least one Holter with a QTc interval >450 msec, and percent of time with QTc >450 msec exceeded published values. The proportion of subjects who received a cardiac pacemaker due to prolonged r-r interval was greater for the children with the 20/27 genotype (67%) than the 20/25 (0%) or 20/26 genotype (25%) (P ¼ 0.01). Among three children who did not receive a cardiac pacemaker, but who had r-r intervals !3 sec, two died suddenly. Conclusions: These results confirm a disturbance of cardiac autonomic regulation in CCHS, indicate that PHOX2B genotype is related to the severity of dysregulation, predict the need for cardiac pacemaker, and offer the clinician the potential to avert sudden death.

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“…We hypothesized that critical disease-related alterations in gene expression might occur only in specific brain regions or neurons, and therefore would be masked in analyses of whole brain tissue. To circumvent this problem, we investigated the hypothalamus because a number of RTT phenotypes (anxiety, growth deceleration, sleep-wake rhythm disturbance, and autonomic abnormalities) could be attributed to hypothalamic dysfunction (9). We performed microarray analysis using hypothalamic RNA from four Mecp2-null males, four MECP2-Tg males, and their respective WT littermates at 6 wks of age using the Affymetrix Mouse Exon 1.0 ST microarray (10,11).…”

mentioning

confidence: 99%

MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription

Chahrour

Jung

Shaw

et al. 2008

Science

1,615

1,596

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Mutations in the gene encoding the transcriptional repressor methyl-CpG binding protein 2 (MeCP2) cause the neurodevelopmental disorder Rett syndrome. Loss of function as well as increased dosage of MECP2 gene cause a host of neuropsychiatric disorders. To explore the molecular mechanism(s) underlying these disorders, we examined gene expression patterns in the hypothalamus of mice that either lack or overexpress MeCP2. In both models, MeCP2 dysfunction induced changes in the expression levels of thousands of genes, but surprisingly the majority of genes (~85%) appeared to be activated by MeCP2. We selected six genes and confirmed that MeCP2 binds to their promoters. Furthermore, we showed that MeCP2 associates with the transcriptional activator CREB1 at the promoter of an activated target but not a repressed target. These studies suggest that MeCP2 regulates the expression of a wide range of genes in the hypothalamus and that it can function as both an activator and repressor of transcription.Rett syndrome (RTT, MIM 312750) is a progressive neurodevelopmental disorder caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2) (1). RTT patients appear to develop normally up to the first year of age after which they lose any acquired speech and replace purposeful hand use with stereotypies. MECP2 mutations also result in a host of neurobehavioral abnormalities, ranging from mild learning disabilities to autism, Xlinked mental retardation, and infantile encephalopathy. Interestingly, an increase in MECP2 dosage is equally detrimental to the nervous system: duplications spanning the MECP2 locus cause features overlapping with those of RTT and related neurological disorders (2).

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Pediatric Autonomic Disorders

Cited by 110 publications

References 104 publications

Mitochondrial Disease in Childhood: Nuclear Encoded

Mitochondrial Disease in Childhood: Nuclear Encoded

Congenital central hypoventilation syndrome: PHOX2B genotype determines risk for sudden death

MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription

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