Abstract
BackgroundMicrodeletions on chromosome 17q12 cause of diverse spectrum of disorders and have only recently been identified as a rare cause of Mayer-Rokitansky-Kuester-Hauser-Syndrome (MRKH), which is characterized by uterus aplasia ± partial/complete vaginal aplasia in females with a regular karyotype. For the first time we report about a patient with a 17q12 microdeletion who is affected by MRKH in combination with a vascular and soft tissue disorder. Repeatedly she suffered from kidney transplant failure caused by consuming membranous nephropathy.Case presentationA 38-year-old female patient had been diagnosed with right kidney aplasia, left kidney dysplasia and significantly impaired renal function during infancy. Aged 16 she had to start hemodialysis. Three years later she received her first kidney transplant. Only then she was diagnosed with MRKH. The kidney transplant was lost due to consuming nephrotic syndrome caused by de novo membranous nephropathy, as was a second kidney transplant years later. In addition, a hyperelasticity syndrome affects the patient with congenital joint laxity, kyphoscoliosis, bilateral hip dysplasia, persistent hypermobility of both elbows, knees and hips. Her clinical picture resembles a combination of traits of a hypermobile and a vascular form of Ehlers-Danlos-Syndrome, but no mutations in the COL3A1 gene was underlying. Instead, array-based comparative genomic hybridisation (CGH) detected a heterozygous 1.43 Mb deletion on chromosome 17q12 encompassing the two renal developmental genes HNF1β and LHX1.ConclusionsDeletions of HNF1β have recently drawn significant attention in pediatric nephrology as an important cause of prenatally hyperechogenic kidneys, renal aplasia and renal hypodysplasia. In contrast, membranous nephropathy represents an often-unaccounted cause of nephrotic syndrome in the adult population. A causative connection between theses two conditions has never been postulated, but is suggestive enough in this case to hypothesize it.
Highlights
Microdeletions on chromosome 17q12 cause of diverse spectrum of disorders and have only recently been identified as a rare cause of Mayer-Rokitansky-Kuester-Hauser-Syndrome (MRKH), which is characterized by uterus aplasia ± partial/complete vaginal aplasia in females with a regular karyotype
Microdeletions on chromosome 17q12 encompassing the hepatocyte nuclear factor 1β (HNF1β) have recently been characterized as an important cause of prenatally hyperechogenic kidneys, renal aplasia and renal hypodysplasia, which represent an important cause of chronic renal failure among children [1,2]
The following case expands the diverse spectrum of disorders associated with 17q12 microdeletions and reveals a hypothetical link with membranous nephropathy (MN), a common and often unaccounted cause of nephrotic syndrome in the adult population
Summary
Mayer-Rokitansky-Kuester-Hauser (MRKH) is a quite common inherited condition (1:4.000-5.000) characterized by uterus aplasia ± partial/complete vaginal aplasia in females with a regular karyotype XX/46 and physiological ovarial function [4,5,6]. In a series of only five published cases, three women presented without (MRKH type I/typical) and two with kidney affection (MRKH type II/atypical) This finding reflects the highly variable clinical picture of even identical 17q12 microdeletions, reaching from diabetes (MODY5 or NODAT, as observed in our patient), to pancreas and liver anomalies, epilepsy, sensorineural hearing loss, cognitive. Our patient developed MN and consuming nephrotic syndrome years after her first, but only weeks after her second kidney transplantation. This clinical course may reflect a boostered alloimmune response against the kidney transplants, or alternatively a boostered response against a physiological glomerular epitope, which had not been expressed in the patient’s native kidney. Competing interest The author(s) declare that they have no competing interest
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