TCF2/HNF-1beta mutations: 3 cases of fetal severe pancreatic agenesis or hypoplasia and multicystic renal dysplasia.

OBJECTIVE: The aim of this study was to document the association between pancreatic agenesis or hypoplasia and multicystic renal dysplasia related to transcription factor 2 (TCF2) or hepatocyte nuclear factor 1 beta mutations. METHODOLOGY: We describe the phenotype of the pancreas and the kidneys from three fetuses heterozygous for a mutation of TCF2. CASES: Case 1 had bilateral hyperechogenic, multicystic kidneys, bilateral clubfoot and pancreatic agenesis. Case 2 had two enlarged polycystic kidneys, anamnios and pancreatic agenesis. Case 3 had multicystic renal dysplasia, oligohydramnios and hypoplasia of the tail of the pancreas. CONCLUSION: TCF2 mutations are frequently discovered in fetuses presenting with bilateral hyperechogenic kidneys. The association between pancreatic agenesis and a TCF2 mutation has not previously been reported. TCF2 deficiency in mice leads to pancreatic agenesis, suggesting that the gene is essential for pancreatic development. Our observations indicate the importance of visualizing the pancreas during ultrasound examinations if renal malformations are discovered.

Prenatal diagnosis of mosaic tetrasomy 8p.

Tetrasomy 8p is a rare chromosomal disorder that has only been detected in a mosaic form. At the present time, 11 cases have been reported; their phenotype included agenesis of the corpus callosum, enlarged ventricles, minor facial dysmorphism, rib and vertebral anomalies, and mild to moderate developmental delay. To the best of our knowledge, tetrasomy 8p has never been prenatally diagnosed. This 43-year-old woman was referred for amniocentesis at 20 weeks' gestation because of advanced maternal age. Amniotic fluid cells were cultured according to standard techniques by the in situ method. A supernumerary chromosomal marker was detected in a single clone of cultured amniotic cells and interpreted by RHG banding as an isochromosome of the short arm of chromosome 8 (i(8p)). The ultrasound investigation at 27 weeks gestation revealed enlarged ventricles and agenesis of the corpus callosum, which were confirmed at fetal autopsy after medical termination of the pregnancy. Chromosomal analyses, including RHG banding and FISH, of several tissues showed different levels of i(8p) mosaicism. Whereas no i(8p) was detected on cytotrophoblast nor additional amniotic fluid cells, 97% and 30% of cells from long-term cultures of placenta and lymphocytes, respectively, had the i(8p). Using DNA markers, the isochromosome 8p was interpreted as the result of a prezygotic event during maternal meiosis. Our findings suggest that the i(8p) is the subject of tissue selection. Tetrasomy 8p might be underdiagnosed during pregnancy; therefore, karyotyping on a fetal blood sample following detection of agenesis of the corpus callosum when no chromosomal abnormality has been found on the amniotic fluid cell cultures should be discussed with the parents.