Ovary
Gonadal dysgenesis
Mixed gonadal dysgenesis
Author: Carolina Sforza, M.D.
Last author update: 1 February 2010
Last staff update: 14 October 2020
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: Mixed gonadal dysgenesis [title]
Table of Contents
Definition / general | Terminology | Etiology | Clinical features | Laboratory | Prognostic factors | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Molecular / cytogenetics description | Differential diagnosis | Additional referencesCite this page: Sforza C. Mixed gonadal dysgenesis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/ovarynontumormixedgonadaldysgenesis.html. Accessed May 30th, 2023.
Definition / general
- Mixed gonadal dysgenesis refers to an individual who usually has a differentiated gonad on one side and a streak gonad or streak testis on the other side
- Either (a) testis plus contralateral streak gonad, (b) testis and contralateral gonadal agenesis, (c) hypoplastic gonads with tubules in one gonad or (d) streak gonad with contralateral tumor
- A type of asymmetrical gonadal dysgenesis due to chromosomal abnormality
- Often mosaicism: 45X / 46XY, 45X / 46XX or 45X / 47XXY; may also have 46XX but missing part of one X chromosome
Terminology
- In 2005, the Chicago Consensus of Intersex Disorders proposed the term "mixed gonadal dysgenesis" to substitute for disorders of sex development, defined by congenital conditions in which the development of chromosomal, gonadal or anatomical sex is altered
- There is much confusion about the nomenclature for patients with gonadal dysgenesis
- Asymmetrical gonadal dysgenesis is the term used if one gonad displays more complete development and can be identified as a testis or ovary (usually is a testis) and the other gonad is a streak
- Streak testis: streak tissue identified at periphery of differentiated testis
- Streak gonad: ovarian type stroma without differentiated gonadal structures
Etiology
- Reproductive system developmental disorder characterized by progressive loss of primordial cells on the developing glands of an embryo
- This loss leads to extremely hypoplastic and dysfuctioning gonads, which are mainly composed of fibrous tissue, hence the name streak glands
- During embryogenesis, the reproductive system is intrinsically conditioned to give rise to a female, unless altered by hormone production
- As a result, if a gonad cannot express hormones, as occurrs with gonadal dysgenesis, the affected person will still develop both internal and external genitalia
- In gonadal dysgenesis, the accompanying hormonal failure prevents the development of secondary sex characteristics in either sex, resulting in the appearance of a sexually infantile female and infertility
Clinical features
- Phenotype may be ambiguous, male, female, Turner-like syndrome or intersex
- Müllerian structures present since no / minimal anti-Müllerian hormone is produced
- Usually bilateral fallopian tubes are present, occasionally vas deferens
- Females may exhibit clitoromegaly; no breast development except with tumors
- Phenotypic males may have short stature, 90 degree penile torsion, undescended testis, chordae without hypospadias, hypospadias or no obvious abnormalities
- Patients with 45X mosaicism are often considered to have a variant of Turner syndrome
- Phenotypic females may develop virilization at puberty, often complete
- High risk for gonadoblastoma (30%) if Y chromosome material is present, which may obliterate testicular elements and cause incorrect diagnosis
- Higher risk for other medical problems, including deficient immunoglobulin levels, aberrant bony development of inner ear structures, cardiovascular and renal anomalies (horseshoe kidney)
Laboratory
- Elevated FSH
- Chomatin negative Barr bodies
- Low immunoglobulins levels
Prognostic factors
- High risk for gonadoblastoma (30%) if Y chromosome material is present, which may obliterate testicular elements and cause incorrect diagnosis
Case reports
- Short stature in phenotypic male with 45X0 / 46XY mosaicism (Nat Clin Pract Endocrinol Metab 2008;4:524)
- Mistaken diagnosis of testicular dysgenesis (Arq Bras Endocrinol Metabol 2010;54:331)
Treatment
- Excise gonads early to prevent tumors
- Hormone replacement therapy
Microscopic (histologic) description
- Prepubertal patients show normal immature testis
- At / after puberty, tubules exhibit mild hypospermatogenesis to total sclerosis
- Streak gonad has ovarian stroma without primordial ovarian follicles
- Streak ovary is streak gonad with primordial follicles and primitive sex cord-like structures with or without germ cell components within the ovarian type stroma, mimicking gonadoblastoma, granulosa cell tumor or Sertoli cell tumors
Microscopic (histologic) images
AFIP images
Mixed gonadal dysgenesis
Molecular / cytogenetics description
- FISH may be helpful (Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2008;25:570)
- Usually no mutations of SRY (Eur J Obstet Gynecol Reprod Biol 2004;115:55) but see J Med Genet 1993;30:655
Differential diagnosis
- True hermaphroditism (ovary has numerous primordial follicles containing primary oocytes, nature of internal or external genitalia is not relevant, Mod Pathol 2002;15:1013)
Additional references
