Maternal inheritance in cyclic vomiting syndrome with neuromuscular disease

Abstract

Cyclic vomiting syndrome (CVS), characterized by severe discrete episodes of nausea, vomiting, and lethargy, is a predominately childhood condition associated with migraine and dysautonomic features. Disease-associated mitochondrial DNA (mtDNA) sequence variants are suggested by a strong maternal bias in the inheritance of migraine, and the recent findings of mtDNA variants in a few children with CVS and additional neuromuscular disease manifestations ("CVS+"). A clinical interview using a questionnaire was administered (generally) to one parent of 62 children with CVS+. Non-senile disease manifestations, including migraine, myopathy, seizures, and dysautonomia-like symptoms, were far more common in matrilineal versus non-matrilineal relatives, including being present in 75% of the mothers versus in only 11% of the fathers (P < 0.001). Overall, maternal inheritance is suggested in 86% of the families (in 65% strongly so). Disease manifestations in subjects and their affected matrilineal relatives are predominately intermittent and consistent with dysautonomia, including increased vital sign fluctuations. Body fluid metabolites and muscle biopsy findings are consistent with mitochondrial dysfunction in most cases tested. We conclude that mtDNA sequence variants are at least risk factors in the development of disease in most children at this "severe" end of the CVS spectrum, likely involving a maternally inherited propensity towards dysautonomia.

Cyproheptadine: A Potentially Effective Treatment for Functional Gastrointestinal Disorders in Children

“…There have been three reports [14][15][16] of children (n = 65) who received cyproheptadine for CVS. Response rates ranged from 40% to 83%.…”

“…Response rates ranged from 40% to 83%. [14][15][16] According to the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, 60 cyproheptadine should be the first-line therapy for prophylaxis of CVS in children younger than age 5 years. However, there is no role of cyproheptadine in acute attack of CVS.…”

“…8 Its efficacy in children with FAP has been reported in a double-blind, placebo-controlled trial, 9 as well as in retrospective studies for treatment of FAP, FD, IBS, and AM. [10][11][12][13][14][15][16] 5-HT is a polyfunctional signaling molecule that serves as a paracrine factor, endocrine hormone, neurotransmitter, and growth factor. 17 Various 5-HT receptor subtypes regulate gut motility, secretion, and visceral sensitivity.…”

Pediatric Migraine Equivalents. Childhood Periodic Syndromes. A Review of Literature and the Authors’ Clinical Observations

“…Принято считать, что периодические синдромы поражают изначально неврологически здоровых детей [17,57]. Тем не менее в последние го-ды описаны случаи развития состояний у пациентов с детским церебральным параличом и генетическими синдромами [12,13]. Безусловно, диагностика ДПС в этих случаях крайне сложна и ответственна [44].…”

“…Авторы предложили для этих случаев ис-пользовать дефиницию «СЦР плюс», полагая, что это самостоятельная клиническая единица среди ДПС, в основе которой лежат иные патогенетические ме-ханизмы, нежели при классическом варианте. В этой связи рассматривается гипотеза, что причиной таких состояний могут быть врожденные митохондриальные или метаболические нарушения [12,55]. Однако без-оговорочное отнесение их к периодическим синдро-мам, т. е. к эквивалентам мигрени, весьма спорно [36].…”