Visceral Neuropathy, Familial, Autosomal Dominant
Clinical Features
Roy et al. (1980) reported a father and 3 sons with chronic idiopathic intestinal pseudoobstruction who had multiple bouts of abdominal colic, abdominal distention, and diarrhea. Histologic examination of ileal and colonic tissue revealed abnormalities in the myenteric plexus, including hyperplastic nerve trunks and ganglion cells, as well as an increased number of ganglion cells. Silver staining showed striking changes in the neurons, some of which were swollen, distorted, and vacuolated; there were also several abnormal, hypertrophied axons. Neurologic examination, including pupillary reflexes, was normal.
Mayer et al. (1986) described a family with visceral neuropathy without extraintestinal manifestations transmitted over at least 4 generations in an autosomal dominant manner. A characteristic dilation of the jejunum and ileum was seen radiographically in 7 affected family members. Histologic studies showed hypertrophy of the smooth muscle, a markedly reduced number of argyrophilic neurons, and degeneration of argyrophilic neurons and nerve fibers, but no Schwann cell proliferation, intranuclear inclusions, or inflammatory cells.
Camilleri et al. (1991) reported a 21-year-old female with repeated episodes of nausea, vomiting, abdominal distention, and pain. Neurologic examination, including pupillary responses, was normal, as were autonomic reflex tests. Manometric examination revealed normal esophageal motility, but there were abnormal patterns in the stomach and small intestine consistent with neuropathic chronic intestinal pseudoobstruction. Histologic specimens from the small intestine showed degenerated neurons within the myenteric plexus but normal smooth muscle; silver staining showed decreased numbers of argyrophilic neurons with swelling and uneven or reduced silver deposition and loss of neuronal processes, consistent with degeneration of enteric neurons. There were also decreased numbers of intrinsic axons within the myenteric plexus. The patient's mother had similar symptoms until her death at age 34; at laparotomy, she had been noted to have an atonic and dilated stomach, distal jejunum and ileum, and the small bowel wall was 'boggy' on palpation. Camilleri et al. (1991) stated that the histologic and radiologic findings in the families reported by Mayer et al. (1986) and Roy et al. (1980) were similar to those observed in their patient.
O'Brien and Smart (1992) reported a family in which 5 of 7 sibs had various abnormalities of esophageal dysmotility and were initially diagnosed with familial esophageal achalasia (200400). Upon follow-up of the family by Roper et al. (2005), 2 individuals had had affected children and the mother had developed symptoms and had abnormalities on electromyography. Seven of the 10 affected family members were available for study; all presented with dysphagia and 2 had repeated episodes of intestinal pseudoobstruction. One patient had a muscle biopsy, which was normal; esophageal and gastric histology from another showed thickened nerve trunks and eosinophilic intranuclear inclusions in the ganglion cells of the myenteric plexus, whereas the smooth muscle was normal. Most of the affected individuals had irregular, asymmetric pupils that were unreactive or reacted very slowly to light and accommodation, and 4 had bilateral nonfatigable ptosis. All had reduced or absent deep tendon reflexes; electromyography in 4 of 5 patients examined showed distally predominant lower motor neuron degeneration/regeneration with no evidence of myopathy. Roper et al. (2005) noted that there is considerable clinical overlap between familial visceral neuropathy and familial visceral myopathy (155310) and that although they can be distinguished histologically, with the former having abnormalities in the myenteric plexus and the latter in the smooth muscle of the gastrointestinal and renal tracts, the 2 conditions might be allelic.
InheritanceFamilial visceral neuropathy may be inherited as an autosomal dominant or autosomal recessive (243180) trait.