Ovary
Disorders of sex development
Sex chromosome DSD
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Last staff update: 15 January 2024
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PubMed Search: Sex chromosome DSD
Cite this page: Sforza C, Ghofrani M. Sex chromosome DSD. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/ovarynontumorsexchromosomeDSD.html. Accessed May 8th, 2024.
Mixed gonadal dysgenesis
Definition / general
Terminology
Etiology
Clinical features
Laboratory
Prognostic factors
Case reports
Treatment
Microscopic (histologic) description
Microscopic (histologic) images
AFIP images
Molecular / cytogenetics description
Differential diagnosis
Additional references
- 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
Turner syndrome
Definition / general
Terminology
Epidemiology
Etiology
Clinical features
Laboratory
Case reports
Treatment
Clinical images
Images hosted on other servers:
Microscopic (histologic) description
Molecular / cytogenetics images
Images hosted on other servers:
- Describes females with a variety of features (most commonly short stature and gonadal insufficiency) associated with loss of an entire X chromosome (45,X0) in about 50%, mosaicism in 15 - 25% and the rest with loss of only a portion of the X chromosome containing the tip of its short arm
Terminology
- Also called Ullrich-Turner syndrome
Epidemiology
- Occurs in about 1:4000 live births
- Increased frequency in abortuses or women with short stature
Etiology
- Haploinsufficiency of genes that are normally expressed by both X chromosomes including:
- "Short stature homeobox containing gene on the X chromosome" (SHOX) in chondrocytes
- Lymphatic gene, leading to absence or hypoplasia of lymphatics, which causes lymphedema, cystic hygroma, webbed neck, low posterior hairline, nail dysplasia and lymphedematous hands and feet at birth
- Multiple genes involved in ovarian function, leading to gonadal dysgenesis and accelerated loss of oocytes at 15 weeks gestation
Clinical features
- Growth failure: short stature with cubitus valgus, genu valgum and short fourth metacarpals (Wikipedia: Cubitus Valgus [Accessed 15 January 2024], Wikipedia: Genu Valgum [Accessed 15 January 2024])
- High palate, prominent ears, chronic otitis media, obstructive sleep apnea, increased sensitivity to noise and problems learning how to suck, blow, eat and articulate (Wikipedia: Turner Syndrome [Accessed 15 January 2024])
- Cardiovascular disease: including bicuspid aortic valve, coarctation of the aorta, partial anomalous pulmonary venous return (PAPVR) and atrial and ventricular septal defects
- Gonadal failure: have female ducts and external genitalia but usually no pubertal development
- Learning disabilities: deficits in visuomotor skills, visual spatial skills, visual and working memory, visual attention, executive functions and social skills
- Associated with nongonadal neoplasms: including atypical polypoid adenomyoma of uterus, endometrial adenocarcinoma, leukemia and soft tissue tumors
Laboratory
- Diagnosis requires a standard 30 cell karyotype
- Markedly elevated serum FSH, reduced serum estrogen
Case reports
- Mother and daughter with nonmosaic Turner syndrome (Fertil Steril 2004;82:923)
Treatment
- Growth hormone (to increase stature) as soon as growth failure occurs
- Cardiac imaging (MRI) at diagnosis and repeated in 5 - 10 year intervals to assess for congenital heart abnormalities and the emergence of aortic dilatation (precursor to aortic dissection)
- Aggressive treatment of hypertension
- Hormone replacement therapy (transdermal estradiol) beginning at normal pubertal age continued to age 50
- Routine neuropsychological testing and family support, including special education
- Also search for hidden Y chromosome mosaicism (J Pediatr Endocrinol Metab 2006;19:1113)
- Follow up medical care for various conditions in adulthood (Endocr Rev 2002;23:120, J Clin Endocrinol Metab 2010;95:1487)
Clinical images
Images hosted on other servers:
Various images
Microscopic (histologic) description
- Streak gonad with fibrous tissue resembling ovarian stroma
Molecular / cytogenetics images
Images hosted on other servers:
45,X0 karyotype
