Renal agenesis, associated genital malformations, and responsible genes

The study of the possible genetic causes complex genital malformations is a subject great interest both to know its etiology and diagnosis for best reproductive advice in these patients. Recently, Chen et al. (1Chen N. Zhao S. Jolly A. Wang L. Pan H. Yuan J. al.Perturbations genes essential Müllerian duct Wölffian development Mayer-Rokitansky-Küster-Hauser syndrome.Am J Hum Genet. 2021; 108: 1-9Abstract Full Text PDF Scopus (22) Google Scholar) published article titled “Perturbations Genes Essential Duct Wolffian Development Mayer-Rokitansky-Kuster-Hauser Syndrome,” this issue Fertility Sterility, Li (2Li Chu C. Lu D. Zheng P. Sheng al.Renal agenesis-related were associated with Herlyn-Werner-Wunderlich syndrome.Fertil Steril. 116: 1360-1369Abstract (2) reported that “whole-exome sequencing revealed renal mutated may be syndrome.” This interesting deserves some comments on agenesis (unilateral [URA] vs. aplasia) as well abnormalities men women responsible genes. We consider 2 different congenital pathologies which there absence or hypoplasia 1 kidneys: aplasia hereditary aplasia/dysplasia (HRAd) due defective metanephric mesenchyme (MM) form kidney; URA distal mesonephric anomalies affecting ureteral bud (UB). Indeed, urinary system closely tract occurs between sixth ninth weeks. A metanephrogenic mass formed intermediate mesoderm, caudally mesonephros, induced by diverticulum UB. UB sprouts dorsal from at opening urogenital sinus grows into mass. stem forms ureter, cranial part expands pelvis, collecting tubules, major minor calyces (3Acién Embryological observations female tract.Hum Reprod. 1992; 74: 437-445Crossref (153) Scholar). Therefore, kidney via reciprocal induction MM. Repetition process induces branching ducts mesenchyme-epithelial differentiation MM generate nephrons. It should also remembered vagina interaction tubercle located sides are those induce correct fusion uterus an anomaly lesion (or hypoplasia, if ectopic ureter), uterine duplication (didelphis, bicornuate septate, less likely), blind atretic hemivagina, ipsilateral agenesis. Naturally, case entire ridge derivatives, will (renal aplasia), ovary (sometimes dysgenetic), fallopian tube hemiuterus. Renal HRAd defining feature description 3 Online Mendelian Inheritance Man syndromes include term hypodysplasia/aplasia (RHDA), but it can present 5 (CAKUT) systematically many other known pathologic combinations without #. Hereditary defined autosomal dominant disorder, incomplete penetrance variable expression, generally malformative combinations; affects mesodermal organs, such heart, lungs, system. However, syndromes, RHDA1 RHDA2 marked having recessive inheritance pattern, whereas RHDA3 CAKUT appointed pattern. In any case, most severe end spectrum usually fetal death within perinatal period. As noted, bilateral, causing death. presence vaginal atresia cryptorchidism has been frequently described; few cases necropsy internal genitalia, uterovaginal (urogenital adysplasia), unicornuate uterus, epididymal cysts deferens have described. Clinically, kidneys utero results oligohydramnios, affected babies observed characteristic facial phenotype Potter’s facies birth. unilateral, patient reach adulthood abnormalities, vesicoureteral reflux, horseshoe kidney, others. Acién (2010) (4Acién P Galán F Manchón I Ruiz E MI Alcaraz LA adysplasia, pulmonary (MRKH) syndrome: report.Orph Rare Dis. 2010; 5: 6Crossref PubMed (21) 17-year-old woman primary amenorrhea syndrome (MRKHS); she had hip dysplasia, cytogenetic comparative hybridization analysis performed yielded normal results. pedigree family was compatible pattern inheritance. Unilateral abnormality women. condition, indicated, impossibility because and/or (although blastema normal). triad malformation, hemivagina women; men, manifests seminal vesicle cyst, ejaculatory obstruction (Zinner syndrome). always (Wolff) derivatives (vagina vesicles men) (uterus) whose proper ducts. These what investigators called others obstructed anomaly; however, we prefer speak (Acien al., 1987) (5Acién Armiñana Garcia-Ontiveros vagina.Arch Gynecol. 1987; 240: 1-8Crossref (25) Scholar), clinically showed large hematocolpos hydrocolpos girls) (Wunderlich syndrome); Gartner pseudocyst upper anterolateral wall communicating uteri (Herlyn-Werner short septum buttonhole; bicornuate-unicollis unilateral cervicovaginal atresia; didelphys/unicornuate unattached cavitated rudimentary horn, atresia, and, naturally, RA (6Acién M.I. history malformation classifications proposal updated system.Hum Reprod Update. 2011; 17: 693-705Crossref (166) Chinese readapted classification, absent inadequate graphs (7Zhu Tong J.L. W. Zhang Lang J.H. New classification syndrome.Chin Med 2015; 128: 222-225Crossref (65) asymptomatic. Symptoms depend existence ureter. ridge, symptoms would contralateral horn (side agenesis). (URA hemivagina) didelphys, manifested groups discussed above, especially first. latter group presents hematometra, retrograde menstruation, endometriosis, worsening removed adnexectomy performed. clinical manifestation permanent incontinence micturition childhood Zinner infertility bilateral vas deferens), cyst stones abscess, hematuria, chronic disease (treated maintenance hemodialysis), fever oliguria. relatively cases. caused compound homozygous heterozygous mutation ITGA8 gene chromosome 10p13. FGF20 8p22, GREB1L 18q11. Congenital DSTYK 1q32, heterogeneity abnormalities. Inductive interactions epithelium through morphogenesis. addition, damage mesoderm (para-axial: muscle skeletal; intermediate: urogenital; lateral: lung, serous membranes) result inappropriate Many expressed epithelial transition identified. MRKHS, identified 12 likely gene-disrupting variants 7 genes: PAX8, BMP4, BMP7, TBX6, HOXA10, EMX2, WNT9B. Other pointed out WNT4, LHX1, HNF1B, patients MRKHS. Moreover, might involved agenesis: retinoic acid receptor coactivator, CFTR syndrome, mutations ADGRG2 linked X chromosome. genes, CHD1L, TRIM32, RET, What happens men? Additionally, note example, seems not Wolff; therefore, participation more doubtful. At moment, continue think genitourinary influenced multifactorial, polygenic, familial mechanisms, together create favorable environment anomaly. very important investigate aspects related malformations, their involvement processes. syndromeFertility SterilityVol. 116Issue 5PreviewTo explore (HWWS) using whole-exome sequencing. Full-Text