Endocrine Abstracts

Introduction: MRKH syndrome is a rare congenital disease, which affects 1/5000 female births. It is usually diagnosed in the course of primary amenorrhea investigation. Characteristics are mullerian agenesis with 46XX karyotype. Only Wnt4 gene (1) was involved in a few cases of MRKH with hyperandrogenism. We describe two new cases with MRKH syndrome and complete deletion of TCF2 gene in the heterozygous state, this gene is also involved in monogenic diabetes type 5.

Case 1: Seventeen year old, primary amenorrhea, karyotype 46XX, normal puberty. Clinical examination: 3 cm vagina, MRI: absence of uterus, normal ovaries. Ultrasound: 7 mm unsignificant kidney cyst. Biological results: normal plasmatic levels of creatinine, liver enzymes and fasting blood glucose (0.72 g/l).

Case 2: Six years old left kidney atrophia, 14 years insulinated diabetes, diagnosis of primary amenorrhea at 17 years old, karyotype: 46XX, normal puberty. At clinical examination: utero-vaginal aplasia. Occurrence of renal deficiency and increase level of liver enzymes during follow up.

Molecular biology: Complete deletion of TCF2 gene in the heterozygous state in these two cases.

Conclusion: TCF2 gene is involved in MODY 5 diabetes, encoding HNF1B a nuclear transcriptional factor expressed in several organs (liver, lung, pancreas, kidney and genital tract). 18% of women with TCF2 mutations have kidney and genital tract abnormalities (bicornuate uterus). To date only three cases have been reported, two siblings in 1999 (4) and a 24 weeks fetus in 2008 (5). It was a partial TCF2 deletion in heterozygous state in these three MRKH syndrome. With this two new cases associating MRKH syndrome and complete TCF2 deletions in the heterozygous state, with an unsignificant renal cyst in one case, we suggest that this gene should be tested, regarding it’s implication during the follow up (renal failure, diabetes, liver enzymes).

References: 1. Sultan, 2009.

2. Reber, 2001.

3. Oram, 2010.

4. Lindner, 1999.

5. Edghill, 2008.