Illness46XX - gonadal dysgenesis, differential diagnosis

NGS +

[Sanger]

Gonadal dysgenesis as in Turner syndrome (45X) can also occur in chromosomal mosaics (45X/46XX, 45X/46XX/47XXX, 45X/46XY). The common phenotype of 46XX gonadal dysgenesis includes normal stature, sexual infantilism, bilateral strand gonads, normal female internal and external genitalia and primary amenorrhoea. The streak gonad produces occasionally oestrogens or androgens, but malignant transformation is rare. Incomplete forms of this condition can lead to hypoplastic ovaries that produce enough oestrogen to cause some breast development and a few menstrual periods, followed by secondary amenorrhoea. This heterogeneous syndrome occurs sporadically, usually with autosomal recessive or dominant inheritance, in some cases it is associated with other congenital malformations. 46XX gonadal dysgenesis also occurs in association with autosomal recessively inherited congenital adrenal hyperplasia, which is usually caused by CYP21A2 mutations. Precursors of 17-hydroxyprogesterone are accumulated, converted to testosterone and cause virilisation of the female genitals. The total diagnostic yield of 46XX gonadal dysgenesis is slightly over 30%. An inconspicuous genetic finding does not mean that the suspected clinical diagnosis can be excluded with certainty.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK539886/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182188/

• Alias: 46XX pure/complete gonadal dysgenesis
• Alias: Hypergonadotropic amenorrhea; Hypergonadotropic hypogonadism
• Allelic: 46XY sex reversal 3 (NR5A1)
• Allelic: Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency (CYP21A2)
• Allelic: Adrenocortical insufficiency (NR5A1)
• Allelic: Combined oxidative phosphorylation deficiency 5 (MRPS22)
• Allelic: D-bifunctional protein deficiency (HSD17B4)
• Allelic: Galloway-Mowat syndrome 7 (NUP107)
• Allelic: Hydrops, lactic acidosis + sideroblastic anemia (LARS2)
• Allelic: Mitochondrial DNA depletion syndrome 7, hepatocerebral type (TWNK)
• Allelic: Nephrotic syndrome, type 11 (NUP107)
• Allelic: Ovarian hyperstimulation syndrome (FSHR)
• Allelic: Ovarian response to FSH stimulation (FSHR)
• Allelic: Premature ovarian failure 4 (BMP15)
• Allelic: Progressive external ophthalmoplegia + mitochondrial DNA deletions, AD 3 (TWNK)
• Allelic: Spermatogenic failure 32 (SOHLH1)
• Allelic: Spermatogenic failure 8 (NR5A1)
• 17,20-lyase deficiency, isolated (CYP17A1)
• 17-alpha-hydroxylase/17,20-lyase deficiency (CYP17A1)
• 46XX sex reversal 4 (NR5A1)
• Allelic: Blepharophimosis, epicanthus inversus, and ptosis, type 1 (FOXl2)
• Allelic: Blepharophimosis, epicanthus inversus, and ptosis, type 2 (FOXl2)
• Allelic: Spermatogenic failure 28 (FANCM)
• Autoimmune polyendocrinopathy syndrome , type I, with/-out reversible metaphyseal dysplasia (AIRE)
• Gonadal Dysgenesis [genecards] (SPIDR)
• Hyperandrogenism, nonclassic type, due to 21-hydroxylase deficiency (CYP21A2)
• Ovarian dysgenesis 1 (FSHR)
• Ovarian dysgenesis 2 (BMP15)
• Ovarian dysgenesis 3 (PSMC3IP)
• Ovarian dysgenesis 4 (MCM9)
• Ovarian dysgenesis 5 (SOHLH1)
• Ovarian dysgenesis 6 (NUP107)
• Ovarian dysgenesis 7 (MRPS22)
• Ovarian dysgenesis 8 (ESR2)
• Perrault syndrome 1 (HSD17B4)
• Perrault syndrome 2 (HARS2)
• Perrault syndrome 3 (CLPP)
• Perrault syndrome 4 (LARS2)
• Perrault syndrome 5 (TWNK)
• Perrault syndrome 6 (ERAL1)
• Premature ovarian failure 14 (GDF9)
• Premature ovarian failure 15 (FANCM)
• Premature ovarian failure 3 (FOXl2)
• Premature ovarian failure 7 (NR5A1)
• Primary ovarian failure [MONDO:0005387] (MSH4)
• Primary ovarian insufficiency [panelapp amber] (NOG)
• Primary ovarian insufficiency [panelapp amber] (POLR2C)
• Primary ovarian insufficiency [panelapp amber] (POLR3H)
• Primary ovarian insufficiency [panelapp green] (MSH4)
• Primary ovarian insufficiency [panelapp green] (SOHLH1)