Martinez-Frias Syndrome

Description

The Martinez-Frias syndrome is characterized by pancreatic hypoplasia, intestinal atresia, and gallbladder aplasia or hypoplasia, with or without tracheoesophageal fistula. There is considerable phenotypic overlap between Martinez-Frias syndrome and Mitchell-Riley syndrome (MTCHRS; 615710), the latter being characterized by neonatal diabetes in addition to the features of the Martinez-Frias syndrome, but without tracheoesophageal fistula (Smith et al., 2010).

Clinical Features

Martinez-Frias et al. (1992) reported a seemingly distinct autosomal recessive syndrome in a brother and sister born to consanguineous Spanish Gypsy parents. The proband was a female infant with hypoplastic pancreas, duodenal atresia, and atresia of the extrahepatic biliary ducts, who died on day 2 of life. A male sib, born 3 years earlier, was reported to have had hypoplastic pancreas and gallbladder, duodenal atresia, hypoplastic intestines, tracheoesophageal fistula, and hypospadias; he died on day 5 of life.

Anneren et al. (1998) described a brother and sister, born of healthy consanguineous parents, with a multiple congenital anomalies (MCA) syndrome that bore both similarities and differences to the syndrome described by Martinez-Frias et al. (1992). Features of the disorder in the sibs included low birth weight, intestinal malrotation, duodenal and esophageal atresia, intra- and extrahepatic biliary atresia, and hypoplastic pancreas. Both children died during infancy, at 25 days and 81 days.

Gentile and Fiorente (1999) described a male infant, born to nonconsanguineous parents, who had tracheoesophageal fistula and duodenal atresia noted at birth. Laparotomy at 9 days of age revealed gastric hypoplasia, annular pancreas causing duodenal stenosis, agenesis of the gallbladder and extrahepatic biliary ducts, intestinal malrotation, and rectoanal atresia. Hypospadias was the only externally detected anomaly. An ostium secundum atrial septal defect was noted on 2-D echocardiography. The patient died of respiratory failure at 10 months of age due to recurrent bronchiolitis.

Molecular Genetics

Exclusion Studies

In the parents of a deceased male infant with Martinez-Frias syndrome, originally described by Gentile and Fiorente (1999), Smith et al. (2010) analyzed the candidate gene RFX6 (612659) and did not find any mutations.