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Illness46XX - disorders of sex development, differential diagnosis

Summary

Short information

A curated panel containing 99 genes (29 guideline-curated genes) for the comprehensive analysis of practically all known geneti causes of 46XX disorders of sex delopment; mutations in 15 genes cover the most frequent mutations.

ID
GP0071
Number of genes
84 Accredited laboratory test
Examined sequence length
22,8 kb (Core-/Core-canditate-Genes)
153,9 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
Material
  • EDTA-anticoagulated blood (3-5 ml)
Diagnostic indications

NGS +

[Sanger]

 

Gene panel

Selected genes

NameExon Length (bp)OMIM-GHeredity
CLPP834AR
CYP11A11566AR
CYP11B11512AR
CYP21A21488AR
FSHR2088AR
HARS21521AR
HSD17B42211AR
LARS22712AR
LHCGR2100AD, AR
POR2043AR
PSMC3IP654AR
RSPO1792AR
SOX91530AD
SRY615XL, YL
WNT41056Sus
AKR1C2420AR
AKR1C4972AR
AMH1683AR
AMHR21722AR
ANOS12043XLR
ATRX7479XL
BMP151179XL
CBX21599AR
CHD78994AD
CYB5A297AR
CYP17A11527AR
CYP19A11512AR
DHCR71428AR
DHH1191AR
DIAPH23306XLD
DUSP61146AD
ESR21593AD
FANCM6147AR
FEZF11428AR
FGF17651AD
FGF8735AD
FGFR12469AR
FLRT31950AD
FOXL21131AD
FSHB390AR
GALT1140AR
GATA41329AD
GDF91365AD, AR
GNRH1291AR
GNRHR987AR
HFM14308AR
HOXA131167AD
HS6ST11236AD
HSD17B3933AR
HSD3B21119AR
IL17RD2220AR
KISS1417AR
LHB426AR
MAMLD12325XLR
MAP3K14539AD
MCM82523AR
MCM93432AR
MRPS221083AR
MSH42811AR
NOBOX2076AD
NOG699AD
NR0B11413XL
NR5A11386AD
NSMF1587AD
NUP1072778AR
PMM2741AR
POLG3720AD, AR
POU5F11083AD
PROK2390AD, AR
PROKR21155AD
SAMD94770AD
SOHLH11164AD, AR
SOX101401AD
SOX31341XL
SPRY4969AD
SRD5A2764AR
STAG33678XL
STAR858AR
TAC3366AR
TACR31398Ass
TWNK2055AD, AR
WDR113675AD
WT11569AD
ZFPM23456AD

Informations about the disease

Clinical Comment

Phenotypic sex is the result of the differentiation of the internal ducts and external genitals under the hormonal influence of the differentiated gonad when the gonad has lost its bipotent state under the influence of sex-determining genes. Disorders of sexual development (DSDs) are defined as congenital conditions in which the development of chromosomal, gonadal and anatomical sex is atypical. Clinical classification in patients is difficult because phenotypes are similar or almost identical, although they may have several etiologies. These conditions can be identified at different lifetimes in foetuses or newborns with unclear external genitalia, gonadal dysgenesis and internal genitalia that are discordant in terms of sex chromosome constitution, and they can also be diagnosed subsequently in people with late puberty, unexpected virilization or gynecomastia, infertility or gonadal tumours. Occasionally DSDs can be part of a genetic syndrome, demonstrating the complexity of sexual development and the effect of multiple genes. DSDs are classified according to changes in the levels of sex determination: Genetic, chromosomal, gonadal, hormonal, ductal sex, external genitals, secondary characteristics, legally assigned sex and psychological characteristics. Molecular genetic analysis currently clarifies little more than half of the DSD problems. All inheritance patterns occur with variable expressivity. An inconspicuous genetic finding does not therefore mean that the clinical suspected diagnosis can be excluded with certainty.

Reference: https://www.karger.com/Article/FullText/499274

 

Synonyms
  • Alias: DSD, disorders of sex determination; Genetic 46XX DSD
  • Alias: Genetic female pseudohermaphroditism
  • Alleic: Progressive external ophthalmoplegia, AR 1 (POLG)
  • Allelic: Acampomelic campomelic dysplasia (SOX9)
  • Allelic: Aldosteronism, glucocorticoid-remediable (CYP11B1)
  • Allelic: Alpha-thalassemia myelodysplasia syndrome, somatic (ATRX)
  • Allelic: Alpha-thalassemia/mental retardation syndrome (ATRX)
  • Allelic: Atrial septal defect 2 (GATA4)
  • Allelic: Atrioventricular septal defect 4 (GATA4)
  • Allelic: Beckwith-Wiedemann syndrome (CDKN1C)
  • Allelic: Blepharophimosis, epicanthus inversus, ptosis, type 1 (FOXL2)
  • Allelic: Blepharophimosis, epicanthus inversus, ptosis, type 2 (FOXL2)
  • Allelic: Brachydactyly, type B2 (NOG)
  • Allelic: Campomelic dysplasia (SOX9)
  • Allelic: Combined oxidative phosphorylation deficiency 5 (MRPS22)
  • Allelic: D-bifunctional protein deficiency (HSD17B4)
  • Allelic: Diaphragmatic hernia 3 (ZFPM2)
  • Allelic: Disordered steroidogenesis due to cytochrome P450 oxidoreductase (POR)
  • Allelic: Encephalocraniocutaneous lipomatosis, somatic mosaic (FGFR1)
  • Allelic: Galloway-Mowat syndrome 7 (NUP107)
  • Allelic: Guttmacher syndrome (HOXA13)
  • Allelic: Hartsfield syndrome (FGFR1)
  • Allelic: Hydrops, lactic acidosis + sideroblastic anemia (LARS2)
  • Allelic: Hypospadias 2, XL (MAMLD1)
  • Allelic: Jackson-Weiss syndrome (FGFR1)
  • Allelic: Leukoencephalopathy with vanishing white matter (EIF2B5)
  • Allelic: Leydig cell adenoma, somatic, with precocious puberty (LHCGR)
  • Allelic: Leydig cell hypoplasia with hypergonadotropic hypogonadism (LHCGR)
  • Allelic: Leydig cell hypoplasia with pseudohermaphroditism (LHCGR)
  • Allelic: Mental retardation-hypotonic facies syndrome, XL (ATRX)
  • Allelic: Mesothelioma, somatic (WT1)
  • Allelic: Mitochondrial DNA depletion syndrome 4A [Alpers type] (POLG)
  • Allelic: Mitochondrial DNA depletion syndrome 4B [MNGIE type] (POLG)
  • Allelic: Mitochondrial DNA depletion syndrome 7 [hepatocerebral type] (TWNK)
  • Allelic: Mitochondrial recessive ataxia syndrome [includes SANDO + SCAE] (POLG)
  • Allelic: Monosomy 7 myelodysplasia and leukemia syndrome 2 (SAMD9)
  • Allelic: Multiple synostoses syndrome 1 (NOG)
  • Allelic: Nephrotic syndrome, type 11 (NUP107)
  • Allelic: Nephrotic syndrome, type 4 (WT1)
  • Allelic: Non-obstructive azoospermia [panelapp] (MSH4)
  • Allelic: Osteoglophonic dysplasia (FGFR1)
  • Allelic: Ovarian hyperstimulation syndrome (FSHR)
  • Allelic: Ovarian response to FSH stimulation (FSHR)
  • Allelic: PCWH syndrome (SOX10)
  • Allelic: Pfeiffer syndrome (FGFR1)
  • Allelic: Precocious puberty, male (LHCGR)
  • Allelic: Progressive external ophthalmoplegia with mitochondrial DNA deletions, AD 3 (TWNK)
  • Allelic: Progressive external ophthalmoplegia, AR 1 (POLG)
  • Allelic: Pseudovaginal perineoscrotal hypospadias (SRD5A2)
  • Allelic: Spermatogenic failure 28 (FANCM)
  • Allelic: Spermatogenic failure 32 (SOHLH1)
  • Allelic: Spermatogenic failure 8 (NR5A1)
  • Allelic: Stapes ankylosis with broad thumbs + toes (NOG)
  • Allelic: Symphalangism, proximal, 1A (NOG)
  • Allelic: Tarsal-carpal coalition syndrome (NOG)
  • Allelic: Tetralogy of Fallot (GATA4)
  • Allelic: Tetralogy of Fallot (ZFPM2)
  • Allelic: Trigonocephaly 1 (FGFR1)
  • Allelic: Tumoral calcinosis, familial, normophosphatemic (SAMD9)
  • Allelic: Ventricular septal defect 1 (GATA4)
  • Allelic: Waardenburg syndrome, type 4C (SOX10)
  • Allelic: Wilms tumor, type 1 (WT1)
  • Allelic:Mitochondrial DNA depletion syndrome 4A, Alpers type (POLG)
  • 17,20-lyase deficiency, isolated (CYP17A1)
  • 17-alpha-hydroxylase/17,20-lyase deficiency (CYP17A1)
  • 46XX sex reversal 1 (SRY)
  • 46XX sex reversal 4 (NR5A1)
  • 46XY gonadal dysgenesis with minifascicular neuropathy (DHH)
  • 46XY sex reversal 1 (SRY)
  • 46XY sex reversal 2, dosage-sensitive (NR0B1)
  • 46XY sex reversal 3 (NR5A1)
  • 46XY sex reversal 5 (CBX2)
  • 46XY sex reversal 6 (MAP3K1)
  • 46XY sex reversal 7 (DHH)
  • 46XY sex reversal 8 (AKR1C2)
  • 46XY sex reversal 8, modifier of (AKR1C4)
  • 46XY sex reversal 9 (ZFPM2)
  • Adrenal hyperplasia, congenital, due to 11-beta-hydroxylase deficiency (CYP11B1)
  • Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency (CYP21A2)
  • Adrenal hyperplasia, congenital, due to 3-beta-hydroxysteroid dehydrogenase 2 deficiency (HSD3B2)
  • Adrenal hypoplasia, congenital (NR0B1)
  • Adrenal insufficiency, congenital, with 46XY sex reversal, partial/complete (CYP11A1)
  • Adrenocortical insufficiency (NR5A1)
  • Allelic: Charcot-Marie-Tooth disease, demyelinating, type 1I (POLR3B)
  • Allelic: Precocious puberty, central, 1 (KISS1R)
  • Allelic: Spastic paraplegia 39, AR (PNPLA6)
  • Antley-Bixler syndrome with genital anomalies + disordered steroidogenesis (POR)
  • Aromatase deficiency (CYP19A1)
  • Aromatase excess syndrome (CYP19A1)
  • Boucher-Neuhauser syndrome (PNPLA6)
  • CHARGE syndrome (CHD7)
  • CHARGE syndrome (SEMA3E)
  • Campomelic dysplasia with autosomal sex reversal (SOX9)
  • Cerebellar ataxia and hypogonadotropic hypogonadism (RNF216)
  • Congenital disorder of glycosylation, type Ia (PMM2)
  • Denys-Drash syndrome (WT1)
  • Disorders of sex development [panelapp] (ATRX)
  • Frasier syndrome (WT1)
  • Galactosemia (GALT)
  • Gordon-Holmes syndrome [GeneReviews] (OTUD4, PNPLA6, RNF216, STUB1)
  • Hand-foot-uterus syndrome (HOXA13)
  • Hyperandrogenism, nonclassic type, due to 21-hydroxylase deficiency (CYP21A2)
  • Hypogonadotropic hypogonadism 1 with/-out anosmia; Kallmann syndrome 1 (ANOS1)
  • Hypogonadotropic hypogonadism 10 with/-out anosmia (TAC3)
  • Hypogonadotropic hypogonadism 11 with/-out anosmia (TACR3)
  • Hypogonadotropic hypogonadism 12 with/-out anosmia (GNRH1)
  • Hypogonadotropic hypogonadism 13 with/-out anosmia (KISS1)
  • Hypogonadotropic hypogonadism 14 with/-out anosmia (WDR11)
  • Hypogonadotropic hypogonadism 15 with/-out anosmia (HS6ST1)
  • Hypogonadotropic hypogonadism 16 with/-out anosmia (SEMA3A)
  • Hypogonadotropic hypogonadism 16 with/-out anosmia (SEMA3A)
  • Hypogonadotropic hypogonadism 17 with/-out anosmia (SPRY1)
  • Hypogonadotropic hypogonadism 18 with/-out anosmia (IL17RD)
  • Hypogonadotropic hypogonadism 19 with/-out anosmia (DUSP6)
  • Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
  • Hypogonadotropic hypogonadism 20 with/-out anosmia (FGF17)
  • Hypogonadotropic hypogonadism 21 with anosmia (FLRT3)
  • Hypogonadotropic hypogonadism 22, with/-out anosmia (FEZF1)
  • Hypogonadotropic hypogonadism 23 with/-out anosmia (LHB)
  • Hypogonadotropic hypogonadism 24 without anosmia (FSHB)
  • Hypogonadotropic hypogonadism 3 with/-out anosmia (PROKR2)
  • Hypogonadotropic hypogonadism 4 with/-out anosmia (PROK2)
  • Hypogonadotropic hypogonadism 5 with/-out anosmia (CHD7)
  • Hypogonadotropic hypogonadism 6 with/-out anosmia (FGF8)
  • Hypogonadotropic hypogonadism 7 without anosmia (GNRHR)
  • Hypogonadotropic hypogonadism 8 with/-out anosmia (KISS1R)
  • Hypogonadotropic hypogonadism 9 with/-out anosmia (NSMF)
  • IMAGE syndrome (CDKN1C)
  • Isolated gonadotropin-releasing hormone deficiency [GeneReviews] (AXL, CCDC141)
  • Laurence-Moon syndrome (PNPLA6)
  • Leukodystrophy, hypomyelinating, 8, +/- oligodontia +/- hypogonadotropic hypogonadism (POLR3B)
  • Lipoid adrenal hyperplasia (STAR)
  • Luteinizing hormone resistance, female (LGCGR)
  • MIRAGE syndrome (SAMD9)
  • Marinesco-Sjogren syndrome (SIL1)
  • Mayer-Rokitansky-Kuster-Hauser syndrome (LHX1)
  • Meacham syndrome (WT1)
  • Mental retardation, XL, with isolated growth hormone deficiency (SOX3)
  • Methemoglobinemia + ambiguous genitalia (CYB5A)
  • Mullerian aplasia + hyperandrogenism (WNT4)
  • Oliver-McFarlane syndrome (PNPLA6)
  • 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)
  • Ovarioleukodystrophy (EIF2B5)
  • Palmoplantar hyperkeratosis + true hermaphroditism (RSPO1)
  • Palmoplantar hyperkeratosis, squamous cell carcinoma of skin, sex reversal (RSPO1)
  • Panhypopituitarism, XL (SOX3)
  • Perrault syndrome 1 (HSD17B4)
  • Perrault syndrome 2 (HARS2)
  • Perrault syndrome 3 (CLPP)
  • Perrault syndrome 4 (LARS2)
  • Perrault syndrome 5 (TWNK)
  • Perrault syndrome 6 (ERAL1)
  • Persistent Mullerian duct syndrome, type I (AMH)
  • Persistent Mullerian duct syndrome, type II (AMHR2)
  • Premature ovarian failure 10 (MCM8)
  • Premature ovarian failure 14 (GDF9)
  • Premature ovarian failure 15 (FANCM)
  • Premature ovarian failure 2A (DIAPH2)
  • Premature ovarian failure 3 (FOXL2)
  • Premature ovarian failure 4 (BMP15)
  • Premature ovarian failure 5 (NOBOX)
  • Premature ovarian failure 7 (NR5A1)
  • Premature ovarian failure 8 (STAG3)
  • Premature ovarian failure 9 (HFM1)
  • Primary ovarian failure [MONDO:0005387] (MSH4)
  • Primary ovarian insufficiency (POU5F1)
  • Primary ovarian insufficiency (SOHLH2)
  • Primary ovarian insufficiency [panelapp] (NANOS3)
  • Primary ovarian insufficiency [panelapp] (NOG)
  • Primary ovarian insufficiency [panelapp] (POLG)
  • Pseudohermaphroditism, male, with gynecomastia (HSD17B3)
  • SERKAL syndrome: 46,XX SEx Reversal with dysgenesis of Kidney, Adrenals, Lungs (WNT4)
  • Smith-Lemli-Opitz syndrome (DHCR7)
  • Spinocerebellar ataxia 48 (STUB1)
  • Spinocerebellar ataxia, AR 16 (STUB1)
  • Testicular anomalies with/-out congenital heart disease (GATA4)
  • Waardenburg syndrome, type 2E, with/-out neurologic involvement (SOX10)
  • Woodhouse-Sakati syndrome (DCAF17)
Heredity, heredity patterns etc.
  • AD
  • AR
  • Ass
  • Sus
  • XL
  • XLD
  • XLR
  • YL
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code
Q52.-

Bioinformatics and clinical interpretation

No text defined