Familial visceral neuropathy: A defined entity?

Abstract

Familial visceral neuropathy (FVN) is a heterogeneous group of disorders due to abnormalities of the myenteric plexus. FVN with neuronal intranuclear inclusions is one particular form of FVN with a variable phenotype that includes achalasia, gastro‐esophageal reflux, intestinal dysmotility and pseudo‐obstruction, dysarthria, peripheral neuropathy and pupillary defects, and the presence of intranuclear inclusions within the neurons of the enteric nervous system. We present a four‐generation family in which 10 individuals (7 of whom have been examined) are affected with FVN. The family was previously reported as familial esophageal achalasia, an autosomal recessive condition (MIM200400). At that time, several individuals in a single sibship were affected and there were no manifestations in either parent. Since that report, two individuals have had affected children and the mother has developed symptoms and has abnormalities on electromyography, thus enabling us to reclassify the family. This family provides further evidence of autosomal dominant inheritance, with marked variation in expression. © 2005 Wiley‐Liss, Inc.

Achalasia: will genetic studies provide insights?

“…In four of these families intranuclear inclusions in the neurons of the ENS have been reported, and this may represent a subform of the disorder (Roper et al 2005). Achalasia was present in three of these four families (Barnett et al 1992;Roper et al 2005;Schuffler et al 1978). An autosomal dominant mode of transmission was observed in two of the FVN-achalasia families (Barnett et al 1992;Roper et al 2005), whereas familial occurrence was suggestive of autosomal recessive inheritance in the third (Schuffler et al 1978).…”

“…Eight families with FVN have been reported in the literature (Barnett et al 1992;Camilleri et al 1991;Faber et al 1987;Mayer et al 1986;Roper et al 2005;Roy et al 1980;Schuffler et al 1978;Zannolli et al 2002). In four of these families intranuclear inclusions in the neurons of the ENS have been reported, and this may represent a subform of the disorder (Roper et al 2005). Achalasia was present in three of these four families (Barnett et al 1992;Roper et al 2005;Schuffler et al 1978).…”

“…The clinical presentation is variable and includes achalasia, gastroesophageal reflux, intestinal dysmotility and pseudoobstruction, dysarthria, peripheral neuropathy, and pupillary defects. Eight families with FVN have been reported in the literature (Barnett et al 1992;Camilleri et al 1991;Faber et al 1987;Mayer et al 1986;Roper et al 2005;Roy et al 1980;Schuffler et al 1978;Zannolli et al 2002). In four of these families intranuclear inclusions in the neurons of the ENS have been reported, and this may represent a subform of the disorder (Roper et al 2005).…”

A novel locus for syndromic chronic idiopathic intestinal pseudo-obstruction maps to chromosome 8q23–q24

“…Two main forms of CIIP are recognized, respectively labeled as myogenic (when smooth muscle cells are affected) or neurogenic (when caused by abnormalities of the enteric nervous system). 8,9 Most patients do not show familial recurrence (sporadic cases) but syndromic autosomal-dominant, 10,11 autosomalrecessive, 12 and X-linked 13,14 forms have been described. In particular, an X-linked locus has been mapped to the Xq28 region.…”

Achalasie im Kindesalter: Eine separate Entität?

“…Gründe sind das alleinige Vorhandensein von Kasuistiken oder kleinen Fallserien in der Literatur sowie die extreme Heterogenität der Erkrankung mit einer ausgeprägten Phäno-typvariabilität, auch innerhalb der gleichen Familie. Eine weitere hereditäre, heterogene Gruppe von Erkrankungen, aufgrund von Alterationen des Plexus myentericus mit entsprechend frühem Beginn einer Achalasie, ist die familiäre viszerale Neuropathie [16]. Die Achalasie wurde in der letzten Zeit kasuistisch als Ausdruck einer neuen mitochondrialen Erkrankung der Kindheit mit multiplen mtDNA-Deletionen, jedoch ohne definierte molekulare Basis, dargestellt, die sich sowohl mit den klinischen Bildern der Achalasie als auch mit weitreichenden neurologischen Verände-rungen manifestieren kann [17].…”