Gonadal dysgenesis is the failure of typical sexual development due to chromosomal and developmental errors. It usually affects the reproductive system as well as the urinary system and encompasses a range of phenotypes.
Affected individuals may have a family history of genetic sexual conditions or infertility. A prenatal history may also reveal maternal increased exposure to androgens. On physical examination findings may be ambiguous or seemingly normal genitalia . Gonads may or may not be palpable. Gonadal dysgenesis (GD) may result in genitalia that is discordant with the genotype, in addition to the presence of streak gonads. Presentation of GD may occur during childhood, adolescence, or at an even later stage, with complaints such as amenorrhea, lack of pubertal development, and infertility.
One type of GD entails disorders that are genetic and are perpetuated by abnormal chromosomes, examples of which are Turner's syndrome and Klinefelter syndrome . These can have variable karyotypes.
Disorders of sex development can either be 46,XX or 46,XY. They take place due to a disruption in the pathways necessary for gonadal and urogenital development. In 46,XY disorders, patients are genotypically male but may have ambiguous genitalia (seen in partial GD) or completely female genitalia (seen in complete GD).
Presentation of those with 46,XX may be that of a phenotypic male, or they may have normal female genitalia but in both cases lack functional ovaries . They may present with primary amenorrhea. Moreover, concomitant renal and lung dysfunction may be found. Anomalies in sexual development arise due to errors in the expression of certain genes, such as R-spondin-1 (RSPO1) or sex-determining region Y (SRY), which may predispose patients to other conditions such as squamous cell carcinoma or excess androgens in utero.
The most commonly reported form of GD is congenital adrenal hypoplasia (CAH) and is often seen after overexposure to external androgens prenatally.
- Pelvic Mass
A 22-year-old female patient with a 46,XY karyotype was admitted to hospital for primary amenorrhea and a pelvic mass. [ncbi.nlm.nih.gov]
In any patient with a premenarchal pelvic mass, karyotyping should be performed. [cureus.com]
Therefore in premenarchal patients with a pelvic mass, the karyotype should be determined. Differential diagnosis for dysgerminoma include diffuse large B cell lymphoma, poorly differentiated carcinoma, embryonal carcinoma and gonadoblastoma. [doi.org]
Patients also manifested a unique syndrome of extragonadal anomalies, including typical facial gestalt, low birth weight, myopathy, rod and cone dystrophy, anal atresia, omphalocele, sensorineural hearing loss, dry and scaly skin, skeletal abnormalities [ncbi.nlm.nih.gov]
- Hip Dislocation
In addition, she had mild mental retardation, severe rotoscoliosis, pectus excavatus, spina bifida occulta, hip dislocation, and long, slender extremities. [ncbi.nlm.nih.gov]
- Peripheral Neuropathy
Homozygous DHH mutations cause a specific peripheral neuropathy in humans with both 46,XY and 46,XX karyotypes. [ncbi.nlm.nih.gov]
- Behavior Problem
Chromosome 8p deletions are associated with a variety of conditions, including cardiac abnormalities, mental, behavioral problems with variable morphotype and genitourinary anomalies in boys. [ncbi.nlm.nih.gov]
A family history and prenatal history are useful in determining whether or not there is a genetic cause, and in exposing the influence of external androgens on the fetus.
As there is a vast differential for gonadal dysgenesis, tests carried out are to narrow down the possible diagnosis. Despite this, there are some cases where a diagnosis is never reached  . Genetic testing and karyotyping may be conducted to determine the genotype of the individual, although it is not routinely performed. Hormonal tests are also done to assess the functionality of gonads and adrenal glands, as CAH is a common GD. Hormonal stimulation tests are utilized in the determination of receptor abnormalities. Urinalysis is also indicated.
The first imaging study done is usually a pelvic ultrasound. This gives information on the internal urogenital structures. Genitograms performed with contrast provide further information on the ductal system of the pelvic organs. Computerized tomography (CT) and magnetic resonance imaging (MRI) are not routinely used.
Individuals for whom all other modalities fail to establish a clear result, surgical exploration via laparoscopy or laparotomy is possible, although laparoscopy is often preferred  . A biopsy of tissue determines its origin and may aid in making a final diagnosis .
- Ahmed SF, Dobbie R, Finlayson AR, et al. Prevalence of hypospadias and other genital anomalies among singleton births; 1988-1997; in Scotland. Arch Dis Child Fetal Neonatal Ed. 2004;89(2):149–151.
- Oliveira RM, Verreschi IT, Lipay MV, Eça LP, Guedes AD, Bianco B. Y chromosome in Turner syndrome: review of the literature. Sao Paulo Med J. 2009;127(6):373–378.
- Ottolenghi C, Omari S, Garcia-Ortis JE, et al. FOXL2 is required for commitment to ovary differentiation. Hum Mol Genet. 2005;14(14):2053-2062.
- MacLaughlin DT, Donahoe PK. Sex determination and differentiation. N Engl J Med. 2004;350(4):367–378.
- Ahmed SF, Cheng A, Dovey L, et al. Phenotypic features, androgen receptor binding, and mutational analysis in 278 clinical cases reported as androgen insensitivity syndrome. J Clin Endocrinol Metab. 2000;85(2):658–665.
- Kim KR, Kwon Y, Joung JY, Kim KS, Ayala AG, Ro JY. True hermaphroditism and mixed gonadal dysgenesis in young children: a clinicopathologic study of 10 cases. Mod Pathol. 2002;15(10):1013–1019.