Meconium ileus refers to intestinal obstruction due to inspissated meconium in the distal ileum and cecum, which develops in utero and presents shortly after birth as a failure to pass meconium (summary by Romi et al., 2012). Meconium ... Meconium ileus refers to intestinal obstruction due to inspissated meconium in the distal ileum and cecum, which develops in utero and presents shortly after birth as a failure to pass meconium (summary by Romi et al., 2012). Meconium ileus is a known clinical manifestation of cystic fibrosis (CF; 219700), and meconium ileus in the absence of CF is a rare phenomenon (summary by Tal et al., 1985).
Tal et al. (1985) reported a consanguineous Bedouin family in which 4 of 12 sibs had meconium ileus with normal sweat electrolytes. Two of the affected sibs also developed chronic diarrhea in infancy, 1 of whom died at ... Tal et al. (1985) reported a consanguineous Bedouin family in which 4 of 12 sibs had meconium ileus with normal sweat electrolytes. Two of the affected sibs also developed chronic diarrhea in infancy, 1 of whom died at 4 months of age from sepsis and severe malnutrition; postmortem examination revealed no pathologic findings consistent with cystic fibrosis. During long-term follow-up of the 3 surviving affected sibs there was no clinical evidence of steatorrhea, repeat smears did not show fat in the stool, and trypsin activity in the stools was qualitatively normal. No pulmonary abnormalities suggestive of CF were found clinically, radiographically, histologically, or on lung function tests. The parents and 8 other sibs were healthy and had normal sweat electrolytes. Romi et al. (2012) stated that intestinal biopsy in 3 of the affected sibs demonstrated normal ganglions and cholinergic neurons.
In a large Bedouin kindred with meconium ileus mapping to chromosome 12p13, originally reported by Tal et al. (1985), Romi et al. (2012) analyzed the candidate gene GUCY2C (601330) and identified homozygosity for a missense mutation (601330.0002) in ... In a large Bedouin kindred with meconium ileus mapping to chromosome 12p13, originally reported by Tal et al. (1985), Romi et al. (2012) analyzed the candidate gene GUCY2C (601330) and identified homozygosity for a missense mutation (601330.0002) in all affected individuals. The mutation was also detected in homozygosity in 4 of 24 unaffected family members; however, partial penetrance of the phenotype was evident in 1 of those individuals: ultrasonography late in pregnancy demonstrated meconium ileus, although the infant did pass stools unassisted after birth. Penetrance of the postnatal meconium ileus phenotype in homozygous individuals was thus 73% (11 affected of 15 homozygous mutants). The mutation was found in heterozygosity in 3 of 240 unrelated Bedouin controls but was not reported in the HapMap or 1000 Genomes databases. In a sporadic patient with severe meconium ileus, born of first-cousin Bedouin parents and negative for homozygosity at the CFTR locus, Romi et al. (2012) identified homozygosity for a 1-bp insertion in the GUCY2C gene (601330.0003) that was not found in the proband's 2 healthy sibs. The authors noted that the sporadic Bedouin patient's haplotype at the GUCY2C locus was different than that of affected individuals from the large Bedouin kindred.