Are there phenotypic manifestations of connective tissue dysplasia syndrome in patients of reproductive age with aplasia of the vagina and uterus?

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OBJECTIVE

On the basis of retrospective and prospective analysis to identify and describe the phenotypic symptom complex in patients of reproductive age with vaginal and uterine aplasia, both at the systemic and tissue levels

MATERIAL AND METHODS

436 patients (main group) with aplasia of the uterus and vagina were examined, the average age was 20—24 years in 67.2% of cases, in 31.2% of cases — up to 19 years inclusive. The 1^st subgroup included 364 patients with aplasia of the vagina and uterus and non-functioning rudiments, the 2^nd subgroup — 42 patients with aplasia of the vagina and uterus and functioning rudiments, and the 3^rd subgroup — 30 patients with the testicular feminization syndrome. The control group included 47 patients of reproductive age without genital malformations who underwent surgical treatment for other gynecological diseases. Anamnesis, results of general clinical, standard laboratory and instrumental examinations, genetic (karyotypic) studies, volumes of surgical interventions, results of immuno-histochemical studies of endometrial glands and stroma and myometrium of functioning uterine rudiments were analyzed.

RESULTS

Patients with Meyer—Rokitansky—Kuster—Hauser syndrome have a high stigma threshold. Malformations of the urinary system can reach 37.4% depending on the severity of the genital malformation and the associated functional disorders — 45—56%, pathology of the musculoskeletal system — 16.7%, congenital bone deformities and defects — 1.3—5.7%, dysfunctional disorders of the gastrointestinal tract due to anatomical changes — 15—16%, eye pathology — 8.3%, minor heart anomalies — 9%, etc. In patients with testicular feminization syndrome the leading manifestation of embryogenesis and early postnatal disorders is a high frequency of hernias — 22.7% which can be explained by receptor-tissue changes in embryogenesis. Functioning rudiments of the uterus can undergo the same pathological processes as the normal uterus (fibroids, endometriosis). The main volume of surgical intervention in patients with uterine and vaginal aplasia is colpopoiesis from the pelvic peritoneum. Patients with testicular feminization syndrome should be screened for karyotype in the presence of inguinal hernias. All girls with a history of inguinal hernias should be examined for karyotype.

CONCLUSION

The phenotypic symptom complex of patients with vaginal and uterine aplasia indicates mesodermal dysmorphopathy in embryogenesis to a greater extent than connective tissue dysplasia syndrome. Patients with 46XX karyotype with uterine and vaginal aplasia and non-functioning uterine rudiments have a more pronounced dysmorphoplastic phenotype compared with patients with uterine and vaginal aplasia and functioning uterine rudiments. In patients with aplasia of the uterus and vagina in the presence of functioning rudiments, compared with patients with “pure” aplasia of the uterus and vagina (without functioning rudiments), functional disorders of the cardiovascular, digestive and urinary systems are more pronounced, which is explained by the prevalence of dysregulatory pathology. For patients with testicular feminization, dysmorphopathic and dysregulatory changes are not characteristic, and a high percentage of inguinal hernias are explained by receptor disorders at the tissue level in early embryogenesis.

Keywords:

aplasia of the vagina and uterus

undifferentiated connective tissue dysplasia

phenotypic markers

uterine rudiments

metalloproteinases

dysmorphogenesis

embryogenesis

Authors:

Smol’nova T.Yu.

Academician V.I. Kulakov National Research Medical Center for Obstetrics, Gynecology and Perinatology

Bobkova M.V.

Omsk State Medical University

Asaturova A.V.

National Medical Research Center for Obstetrics, Gynecology and Perinatology named after academician V.I. Kulakov

ORCID: 0000-0001-8739-5209

Faizullina N.M.

Academician V.I. Kulakov National Research Medical Center for Obstetrics, Gynecology and Perinatology

Nechaeva G.I.

Omsk State Medical University

Received:

22.08.2020

Accepted:

25.09.2020

List of references:

Schweigmann G. Geley TE, Gassner I. Female genital anomalies and important ovarian conditions. Chapter in book: Pediatric Urogenital Radiology. Medical Radiology. Springer: Cham. 2018;317-352. https://doi.org/10.1007/978-3-319-39202-8_19
Bombard DS, 2nd, Mousa SA. Mayer-Rokitansky-Kuster-Hauser syndrome: complications, diagnosis and possible treatment options: a review. Gynecol Endocrinol. 2014;30:9:618-623. https://doi.org/10.3109/09513590.2014.927855
Patnaik SS, Brazile B, Dandolu V, Ryan PL, Liao J. Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome: A historical perspective. Gene. 2015;555:1:33-40. https://doi.org/10.1016/j.gene.2014.09.045
Adamyan LV, Darenkov SP, Shelygin YuA, Glybina TM, Uvarova EV, Kumykova ZKh, Gadzhieva ZA, Makiyan ZN. Clinical observation of congenital anomaly of the pelvic organs of the cloacal type. Akusherstvo i ginekologiya. 2012;8:1:60-63. (In Russ.).
Connell MT OCM, Segars JH. Genetic syndromes and genes invovlved in the development of the female reproductive tract: a possible role for gene therapy. J Genet Syndr Gene Ther. 2013;4:2.
Fontana L, Gentilin B, Fedele L, Gervasini C, Miozzo M. Genetics of Mayer—Rokitansky—Kuster—Hauser (MRKH) syndrome. Clin Genet. 2017;91:2:233-246. https://doi.org/10.1111/cge.12883
Bobkova MV, Baranova EE, Adamyan LV. Genetic aspects of vagina and the uterus aplasia: the history. Problemy reproduktsii. 2015;21:3:10-15. (In Russ.).
Londra L, Chuong FS, Kolp L. Mayer—Rokitansky—Kuster—Hauser syndrome: a review. Int J Womens Health. 2015;7:865-870. https://doi.org/10.2147/IJWH.S75637
Fliegner M, Krupp K, Brunner F, Rall K, Brucker SY, Briken P. Sexual life and sexual wellness in individuals with complete androgen insensitivity syndrome (CAIS) and Mayer—Rokitansky—Kuster—Hauser syndrome (MRKHS). J Sex Med. 2014;11:3:729-742. https://doi.org/10.1111/jsm.12321
Vunder PA. Gender endocrinology. In sciense., ed. M. 1980. (In Russ.).
Golubeva IV. Hermaphroditism. M.: Meditsina. 1980. (In Russ.).
Edmonds DK, Rose GL, Lipton MG, Quek J. Mayer—Rokitansky—Kuster—Hauser syndrome: a review of 245 consecutive cases managed by a multidisciplinary approach with vaginal dilators. Fertil Steril. 2012;97:3:686-690. https://doi.org/10.1016/j.fertnstert.2011.12.038
Nakhal RS, Creighton SM. Management of vaginal agenesis. J Pediatr Adolesc Gynecol. 2012;25:6:352-357. https://doi.org/10.1016/j.jpag.2011.06.003
Friedler S, Grin L, Liberti G, Saar-Ryss B, Rabinson Y, Meltzer S. The reproductive potential of patients with Mayer-Rokitansky-Kuster-Hauser syndrome using gestational surrogacy: a systematic review. Reprod Biomed Online. 2016;32:1:54-61. https://doi.org/10.1016/j.rbmo.2015.09.006
Rall K, Eisenbeis S, Henninger V, Henes M, Wallwiener D, Bonin M. Typical and atypical associated findings in a group of 346 patients with Mayer—Rokitansky—Kuster—Hauser syndrome. J Pediatr Adolesc Gynecol. 2015;28:5:362-368. https://doi.org/10.1016/j.jpag.2014.07.019
Oppelt PG, Lermann J, Strick R, Dittrich R, Strissel P, Rettig I. Malformations in a cohort of 284 women with Mayer—Rokitansky—Kuster—Hauser syndrome (MRKH). Reprod Biol Endocrinol. 2012;10:57. https://doi.org/10.1186/1477-7827-10-57
Martynov AI, Nechaeva GI, Akatova EV, Vershinina MV, Viktorova IA, Gol’tsova LG, Gromova OA, Delov RA, Drokina OV, Druk IV, Dubilei GS, Ivanova DS, Ivanova IL, Kalinina IYu, Kononova NYu, Kudinova EG, Lalov YuV, Lisichenko OV, Loginova EN, Lyalyukova EA, Maksimov VN, Nagaeva TA, Nadei EV, Moskvina YuV, Pervichko EI, Plotnikova OV, Ponomareva DA, Potapov VV, Ryapolova EA, Savel’eva IV, Svechnikova NN, Seleznev AV, Semenkin AA, Semenova EV, Smol’nova TYu, Smyalovskii VE, Tereshchenko YuV, Troshin IYu, Tyurin AV, Khusainova RI, Tsukanov AYu, Chindareva OI, Shilova MA, Shupina MI, Temnikova EA. Guide of the Russian Scientific Medical Society of Internal Medicine on the diagnosis, treatment and rehabilitation of patients with the connective tissue dysplasia (First edition). Meditsinskii vestnik Severnogo Kavkaza. 2018;13:1-2:137-209. (In Russ.). https://doi.org/10.14300/mnnc.2018.13037
Smol’nova TYu, Buyanova SN, Savel’eva SV. Phenotypic symptom complex of connective tissue dysplasia. Clinical Medicine. 2003;843-847. (In Russ.).
Zemtsovskii EV, Anastas’eva VG, Belan YuB, Brzheskii VV, Viktorova IA, Vereshchagina GN, Vysokogorskii VE, Gendlin GE, Gorbunova VN, Glotov AV, Gnusaev SF, Gromova OA, Evsev’eva ME, Kadurina TI, Karpov RS, Klemenov AV, Martynov AI, Mazurov VI, Storozhakov GI, Konev VP, Konenkov VI, Makolkin VI, Medvedev VP, Mikhailovskii MV, Nesterenko ZV, Nechaeva GI, Nikolaev KYu, Perekalskaya MA, Peretolchina TF, Suvorova AV, Trisvetova EL, Ul’rikh EV, Tsekhanovich VN, Tsukanov YuT, Chernyshova TV, Shabalov NP, Yagoda AV, Yakovlev VM, Abbakumova LN, Arsent’ev VG, Belyaeva EL, Vershinina MV, Gladkikh NN, Druk IV, Krasavina DA, Lobanov MYu, Lyalyukova EA, Mazurova LE, Malev EG, Parfenova NN, Potapov VV, Reeva SV, Rozhdestvenskii AS, Nikulina GP, Rudoi AS, Smol’nova TYu, Smyalovskii VE, Statovskaya EE, Sturov VG, Sulimov AF, Shvetsova EV. Hereditary connective tissue disorders in cardiology. Diagnostics and treatment. Russian recommendations (I revision). Kardiovaskulyarnaya terapiya i profilaktika. 2009;8:6:2-24. (In Russ.).
Patent for invention No. 2585739 dated May 25, 2015. Published: 10.06.16. Bul. No. 16. A new method of surgery for peritoneal colpopoiesis, performed for the surgical correction of malformation of internal genital organs — aplasia of the vagina and uterus. (In Russ.).
Patent for invention No. 2587723 dated July 3, 2015. Publ. 06/20/2016. Bul. No. 17. An improved technique for the operation of colpopoiesis from the pelvic peritoneum with laparoscopic assistance. (In Russ.).
Lalatta F, Motta F, Restelli E, Bellini M, Miozzo M, Gervasini C, Dallapiccola B. Gentilin B & Fedele, L. Dysmorphologic assessment in 115 Mayer-Rokitansky-Kuster-Hauser patients. Clin Dysmorphol. 2015;24:3:95-101. https://doi.org/10.1097/MCD.0000000000000087
Touzon MS, Garrido NP, Marino R, Ramirez P, Costanzo M, Guercio G. Androgen insensitivity syndrome: clinical phenotype and molecular analysis in a single tertiary center cohort. J Clin Res Pediatr Endocrinol. 2019;11:1:24-33. https://doi.org/10.4274/jcrpe.galenos.2018.2018.0185
Listyasari NA, Robevska G, Santosa A, Bouty A, Juniarto AZ, van den Bergen J, Katie L, Ayers AH, Sinclair S, Mh Faradz. Genetic analysis reveals complete androgen insensitivity syndrome in female children surgically treated for inguinal hernia. J Invest Surg. 2019;4:1-7. https://doi.org/10.1080/08941939.2019.1602690
Adamyan LV, Borovaya TG, Makiyan ZN, Bobkova MV. Results of microscopic and immunohistochemical examination of uterine rudiments in patients with uterine and vaginal aplasia (Mayer—Rokitansky—Kuster—Hauser syndrome). Problemy reproduktsii. 2007;13:6:71-77. (In Russ.).
Rall K, Barresi G, Wallwiener D, Brucker SY, Staebler A. Uterine rudiments in patients with Mayer—Rokitansky—Kuster—Hauser syndrome consist of typical uterine tissue types with predominantly basalis-like endometrium. Fertil Steril. 2013;99:5:1392-1399. https://doi.org/10.1016/j.fertnstert.2012.12.002
Brucker SY, Eisenbeis S, Konig J, Lamy M, Salker MS, Zeng N, Seeger H, Henes M, Schöller D, Schönfisch B, Staebler A, Taran F-A, Wallwiener D, Rall K. Decidualization is impaired in endometrial stromal cells from uterine rudiments in Mayer—Rokitansky—Kuster—Hauser syndrome. Cell Physiol Biochem. 2017;41:3:1083-1097. https://doi.org/10.1159/000464116
Kan NE, Klimantsev IV, Dubova EA, Amiraslanov EYu, Sannikova MV, Sergunina OA, Pavlov KA, Shchegolev AI, Tyutyunnik VL. Placental insufficiency in pregnant women with undifferentiated connective tissue dysplasia. Akusherstvo i ginekologiya. 2013;3:54-57. (In Russ.).
Timofeev EV, Zemtsovsky EV, Reeva SV, Malev EG, Lobanov MY, Belyaeva EL, Parfenova NN, Vyutrikh EV, Khasanova SI, Davtyan KR. Algorithms of diagnostics of widespread dysplastic syndromes and phenotypes. Theoretical approaches and practical application of classiﬁcation. Arterial’naya gipertenziya. 2009;15:2:162-165. (In Russ.). https://doi.org/10.18705/1607-419X-2009-15-2-162-165

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