McIndoe Vaginoplasty in MRKHS: Case Report and Literature Review.

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a rare congenital disorder characterized by agenesis of the uterus and upper two-thirds of the vagina. It affects around 1 in 4000-5000 females and is of two types: type 1, also known as isolated Müllerian aplasia or Rokitansky, which involves only uterovaginal agenesis, and type 2, presents as uterovaginal agenesis along with renal, cardiac, and other organ anomalies. Despite the absence of vaginal and uterine structures, individuals with MRKHS typically present with normal secondary sexual characteristics and ovarian functions. A 26-year-old female presented with primary amenorrhea. Despite this, she had typical secondary sexual characteristics. Physical examination revealed normal pubic hair distribution and external genitalia, consistent with Tanner's stage 5 development. Further evaluation via magnetic resonance imaging (MRI) confirmed diagnosis of MRKHS type II, revealing the absence of the uterus and upper two-thirds of the vagina, with normal ovaries and absent left kidney. A multidisciplinary team performed McIndoe vaginoplasty creating a successful neovagina, measuring 7 cm in length, using split-thickness skin graft. MRKHS, a rare congenital anomaly involving Müllerian duct abnormalities, poses diagnostic and therapeutic challenges. The etiology remains unknown, but it likely stems from defective Müllerian fusion during embryologic development. Differential diagnosis from conditions like androgen insensitivity syndrome (AIS) is crucial. MRI is important in diagnosis, revealing associated anomalies. Treatment aims to restore sexual function. This case presents that MRKHS can occur with normal hormonal function and typical secondary sexual characteristics. Neovagina creation is an effective surgical intervention for young females seeking to restore sexual function.

Shah NA ，Yadav M ，Verma S ，Yadav D ，Yadav AK ，Ghimire A ，Rijal H ，Koirala P ... -  《Clinical Case Reports》

MAYER-ROKITANSKY-KUSTER-HAUSER SYNDROME. LAPAROSCOPIC SIGMOID VAGINOPLASTY FOR THE TREATMENT OF VAGINAL AGENESIS - SINGLE CENTER EXPERIENCE IN GEORGIA. CASE REPORT.

Elgandashvili D ，Kalantarov A ，Gugeshashvili T 《-》

Perturbations of genes essential for Müllerian duct and Wölffian duct development in Mayer-Rokitansky-Küster-Hauser syndrome.

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is associated with congenital absence of the uterus, cervix, and the upper part of the vagina; it is a sex-limited trait. Disrupted development of the Müllerian ducts (MD)/Wölffian ducts (WD) through multifactorial mechanisms has been proposed to underlie MRKHS. In this study, exome sequencing (ES) was performed on a Chinese discovery cohort (442 affected subjects and 941 female control subjects) and a replication MRKHS cohort (150 affected subjects of mixed ethnicity from North America, South America, and Europe). Phenotypic follow-up of the female reproductive system was performed on an additional cohort of PAX8-associated congenital hypothyroidism (CH) (n = 5, Chinese). By analyzing 19 candidate genes essential for MD/WD development, we identified 12 likely gene-disrupting (LGD) variants in 7 genes: PAX8 (n = 4), BMP4 (n = 2), BMP7 (n = 2), TBX6 (n = 1), HOXA10 (n = 1), EMX2 (n = 1), and WNT9B (n = 1), while LGD variants in these genes were not detected in control samples (p = 1.27E-06). Interestingly, a sex-limited penetrance with paternal inheritance was observed in multiple families. One additional PAX8 LGD variant from the replication cohort and two missense variants from both cohorts were revealed to cause loss-of-function of the protein. From the PAX8-associated CH cohort, we identified one individual presenting a syndromic condition characterized by CH and MRKHS (CH-MRKHS). Our study demonstrates the comprehensive utilization of knowledge from developmental biology toward elucidating genetic perturbations, i.e., rare pathogenic alleles involving the same loci, contributing to human birth defects.

Chen N ，Zhao S ，Jolly A ，Wang L ，Pan H ，Yuan J ，Chen S ，Koch A ，Ma C ，Tian W ，Jia Z ，Kang J ，Zhao L ，Qin C ，Fan X ，Rall K ，Coban-Akdemir Z ，Chen Z ，Jhangiani S ，Liang Z ，Niu Y ，Li X ，Yan Z ，Wu Y ，Dong S ，Song C ，Qiu G ，Zhang S ，Liu P ，Posey JE ，Zhang F ，Luo G ，Wu Z ，Deciphering Disorders Involving Scoliosis and COmorbidities (DISCO) study group ，Su J ，Zhang J ，Chen EY ，Rouskas K ，Glentis S ，Bacopoulou F ，Deligeoroglou E ，Chrousos G ，Lyonnet S ，Polak M ，Rosenberg C ，Dingeldein I ，Bonilla X ，Borel C ，Gibbs RA ，Dietrich JE ，Dimas AS ，Antonarakis SE ，Brucker SY ，Lupski JR ，Wu N ，Zhu L ... -  《-》

Unveiling the Unknown: Nicaragua's First Recorded Case of Mayer-Rokitansky-Küster-Hauser Syndrome.

Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a congenital disorder affecting the female reproductive system, primarily characterized by the absence or underdevelopment of the uterus and upper two-thirds of the vagina, with preserved ovarian function and normal secondary sexual characteristics. It is a rare disease though prevalence may vary based on genetic and environmental factors. This report details a case of a 26-year-old female patient with a history of smoking, alcohol use, and prior inguinal hernioplasty, presenting with primary amenorrhea and inability to engage in vaginal intercourse. The physical examination revealed signs of androgenic acne, acanthosis in the breasts, Tanner stage 4 breast development, and a reduced clitoral hood. An imperforate hymen was confirmed upon clinical examination. Pelvic ultrasound showed a hypoplastic uterus. Laboratory findings indicated hypogonadotropic hypogonadism, and genetic testing ruled out Turner syndrome and imperforate hymen. The next step was magnetic resonance imaging (MRI) which confirmed uterine hypoplasia and vaginal too, leading to the diagnosis of MRKH syndrome. The patient underwent successful CO2 laser vaginoplasty, and psychological support was provided to address the emotional and social aspects related to the diagnosis. This case, being the first documented in Nicaragua, highlights the importance of early diagnosis and a personalized treatment approach that addresses both the physical and emotional aspects of patients. Additionally, it underscores the need for close collaboration between various specialties including gynecology, endocrinology, genetics, and psychology to ensure comprehensive and optimal clinical and emotional outcomes in the management of patients with MRKH syndrome.

Garcia MES ，Rivera A ，Vargas Salgado CM ，Romero C ，Aragón Conrado LE ，Moreno Cabrera CS ... -  《Cureus》

A rare case: Neovagina creation using McIndoe technique and total surgical approach in a patient with Mayer-Rokitansky-Küster-Hauser syndrome.

Sevinç K ，Kulhan M ，Çelik Ç 《-》