Recurrent microdeletion at 17q12 as a cause of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: two case reports

Abstract

Background: Mayer-Rokitansky-Kuster-Hauser syndrome (MRKH) consists of congenital aplasia of the uterus and the upper part of vagina due to anomalous development of Müllerian ducts, either isolated or associated with other congenital malformations, including renal, skeletal, hearing and heart defects. This disorder has an incidence of approximately 1 in 4500 newborn girls and the aetiology is poorly understood.

Variable phenotype in 17q12 microdeletions: Clinical and molecular characterization of a new case

“…Recently, two additional patients have been reported by Dixit et al (Dixit et al, 2012), with variable neurocognitive involvement. Very interesting, rarely dysmorphic features for these patients have been documented (Bernardini et al, 2009;Moreno-De Luca and SGENE Consortium, 2010). Thus, with the evidence reported to date, the 17q12 deletions seem to be responsible for a wide range of phenotypes with considerable variability in expressivity and penetrance.…”

“…Mutational analysis of LHX1 gene has been performed as already reported in Bernardini et al (Bernardini et al, 2009).…”

“…This syndrome is defined in 46,XX women by congenital absence of the uterus and upper part of the vagina with otherwise normal sexual development and can be associated with renal, skeletal and/or hearing defects (Bernardini et al, 2009;Nik-Zainal et al, 2011 The 17q12 microdeletions are not characterized by intellectual disability or other neurobehavioral phenotypes, while it was observed that the duplication of the same region causes intellectual disability, autism spectrum disorder and speech delay (Brandt et al, 2012). Although earlier reports of cases with the 17q12 microdeletion syndrome did not include cognitive impairment as a part of the characteristic phenotype of these deletions (Mefford et al, 2007), recently, some authors (Dixit et al, 2012;Loirat et al, 2010;Mukamel et al, 2011) have reported rare cases with intellectual impairment, with or without autism, suggesting that cognitive impairment and a behavioral phenotype could be part of the clinical features conveyed by the 17q12 microdeletion.…”

Hepatocyte Nuclear Factor 1β–Associated Kidney Disease

“…This indicates HNF1B as a candidate gene for Mayer-Rokitansky-Küster syndrome, as was suggested in publications preceding the description of genital abnormalities in renal cysts and diabetes syndrome. 30 Hypospadia and other genital abnormalities are sporadically described in male individuals. These may be coincident findings, or they may be part of the CAKUT spectrum described above, in which HNF1B mutations are the most commonly identified genetic cause.…”

Gestational surrogacy and the role of routine embryo screening: Current challenges and future directions for preimplantation genetic testing

“…Such observations have placed WNT4 forward in the group of genes thought to be responsible for proper organization of the female sexual organs. Unfortunately, detailed screening for mutations of some genes in MRKH patients initially failed to identify any consistent alteration which could be regarded as causative (Bernardini et al, 2009). Subsequent work (Ledig et al, 2011) found three regions (1q21.1, 17q12, and 22q11.21) of particular interest, suggesting that deletions and/or missense mutations in LHX1 and HNF1B are also strong gene candidates in MRKH.…”