Klinische FragestellungPränatale DSD, Differentialdiagnose

NGS +

[Sanger]

DSD sind selten pränatal vorhanden, stellen sehr komplexe situationen dar, Management sollte von hochspezialisierten Teams geleitet werden, damit alle Aspekte der Diagnose, Behandlung und ethischen Fragen berücksichtigt werden können. Weiblicher Fötus (Klitorismegalie mit normalen Schamlippen); männlicher Fötus (Mikropenis, Hypospadie, nicht absteigende Hoden, bifides Skrotum). Assoziierte Anomalien: Chromosomal, hauptsächlich Trisomie 13, Triploidie, 13q-Syndrom, in wenigen Fällen. Die Erkrankung ist häufig mit genetischen Syndromen (Smith-Lemli-Opitz + WAGR-Syndromen) assoziiert, andere Defekte, vor allem Gesichtsspalten + Herzfehler werden häufig gefunden.

• Alias: Prenatal disorders of sex determination + differentiation
• Allelic Premature ovarian failure 3 (FOXL2)
• Allelic: Adrenocortical insufficiency (NR5A1)
• Allelic: Beckwith-Wiedemann syndrome (CDKN1C)
• Allelic: Congenital heart defects, multiple types, 4 (NR2F2)
• Allelic: Craniosynostosis 3 (TCF12)
• Allelic: Encephalitis/encephalopathy, mild, with reversible myelin vacuolization (MYRF)
• Allelic: Hemochromatosis, type 4 (SLC40A1)
• Allelic: Histiocytosis-lymphadenopathy plus syndrome (SLC29A3)
• Allelic: Hypospadias 1, XL (AR)
• Allelic: Neurodevelopmental disorder, brain anomalies with/-out vertebral/cardiac anomalies (DHX37)
• Allelic: Short-rib thoracic dysplasia 3 with/-out polydactyly (DYNC2H1)
• Allelic: Short-rib thoracic dysplasia 3 with/-out polydactyly (DYNC2I1)
• 17,20-lyase deficiency, isolated (CYP17A1)
• 17-alpha-hydroxylase/17,20-lyase deficiency (CYP17A1)
• 46,XX sex reversal 5 (NR2F2)
• 46XX sex reversal 1 (SRY)
• 46XX sex reversal 4 (NR5A1)
• 46XY partial gonadal dysgenesis, with minifascicular neuropathy (DHH)
• 46XY sex reversal 1 (SRY)
• 46XY sex reversal 11 (DHX37)
• 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 or complete (CYP11A1)
• Aldosteronism, glucocorticoid-remediable (CYP11B1)
• Androgen insensitivity (AR)
• Androgen insensitivity, partial, with/-out breast cancer (AR)
• Antley-Bixler syndrome with genital anomalies + disordered steroidogenesis (POR)
• Aromatase deficiency (CYP19A1)
• Aromatase excess syndrome (CYP19A1)
• Bardet-Biedl s. (ARL6, BBS1, 10, 12, 2, 4, 5, 7, 9, LZTFR1, MKKS, MKS1, SDCCAG8, TMEM67, TTC()
• Beare-Stevenson cutis gyrata syndrome (FGFR2)
• Blepharophimosis, epicanthus inversus + ptosis, type 1 + 2 (FOXL2)
• CHARGE syndrome (CHD7)
• Campomelic dysplasia with autosomal sex reversal (SOX9)
• Cardiac-urogenital syndrome (MYRF)
• Cong. anomalies of kidney + urinary tract +/- hearing loss, abnormal ears/developmental delay (PBX1)
• Cryptorchidism INSL3)
• Culler-Jones syndrome (GLI2)
• Denys-Drash syndrome (WT1)
• Desmosterolosis (DHCR24)
• Disordered steroidogenesis due to cytochrome P450 oxidoreductase (POR)
• Endocrine-cerebroosteodysplasia (CILK1)
• Fraser syndrome 1 (FRAS1)
• Fraser syndrome 2 (FREM2)
• Fraser syndrome 3 (GRIP1)
• Frasier syndrome (WT1)
• Genitopatellar syndrome )KAT6B)
• Genitourinary and/or brain malformation syndrome (PPP1R12A)
• Glucocorticoid resistance (NR3C1)
• Guttmacher syndrome (HOXA13)
• Hand-foot-uterus syndrome (HOXA13)
• Hemochromatosis, type 3 (TFR2)
• Hydranencephaly with abnormal genitalia (ARX)
• 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 12 with/-out anosmia (GNRH1)
• Hypogonadotropic hypogonadism 14 with/-out anosmia (WDR11)
• Hypogonadotropic hypogonadism 17 with/-out anosmia (SPRY4)
• Hypogonadotropic hypogonadism 18 with/-out anosmia (IL17RD)
• Hypogonadotropic hypogonadism 2 with/-out anosmia (FGFR1)
• Hypogonadotropic hypogonadism 22, with/-out anosmia (FEZF1)
• Hypogonadotropic hypogonadism 23 with/-out anosmia (LHB)
• Hypogonadotropic hypogonadism 24 without anosmia (FSHB)
• Hypogonadotropic hypogonadism 26 with/-out anosmia (TCF12)
• 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)
• Hypogonadotropic hypogonadism []panelapp] (HAMP)
• Hypospadias 2, XL (MAMLD1)
• Hypothyroidism, congenital, due to thyroid dysgenesis or hypoplasia (PAX8)
• IMAGE syndrome (CDKN1C)
• Intellectual developmental disorder, XL, syndromic, 35 (RPL10)
• Leydig cell hypoplasia with hypergonadotropic hypogonadism (LHCGR)
• Leydig cell hypoplasia with pseudohermaphroditism (LHCGR)
• Linear skin defects with multiple congenital anomalies 1 (HCCS)
• Lipoid adrenal hyperplasia (STAR)
• Luteinizing hormone resistance, female (LHCGR)
• MIRAGE syndrome (SAMD9)
• Meacham syndrome (WT1)
• Mental retardation, XL, syndromic 15 [Cabezas type] (CUL4B)
• Mental retardation-hypotonic facies syndrome, XL (ATRX)
• Methemoglobinemia and ambiguous genitalia (CYB5A)
• Microcephaly, facial dysmorphism, renal agenesis + ambiguous genitalia syndrome (CTU2)
• Microphthalmia, syndromic 3 (SOX2)
• Mullerian aplasia and hyperandrogenism (WNT4)
• Nephrotic syndrome, type 14 (SSGPL1)
• Nivelon-Nivelon-Mabille [chondrodysplasia-pseudohermaphroditism] syndrome (HHAT)
• Normosmic IHH, idiopathic Hypogonadotropic hypogonadism [panelapp] (CCDC141)
• Opitz GBBB syndrome, type II (SECC1L)
• Ovarian dysgenesis 8 (ESR2)
• PCWH syndrome (SOX10)
• Palmoplantar hyperkeratosis + true hermaphroditism (RSPO1)
• Palmoplantar hyperkeratosis with squamous cell carcinoma of skin + sex reversal (RSPO1)
• Panhypopituitarism, XL (SOX3)
• Perrault syndrome 2 (HARS2)
• Persistent Mullerian duct syndrome, type I (AMH)
• Persistent Mullerian duct syndrome, type II (AMHR2)
• Peters-plus syndrome (B3GLCT)
• Pituitary hormone deficiency, combined, 2 (PROP1)
• Pituitary hormone deficiency, combined, 4 (LHX4)
• Pontocerebellar hypoplasia, type 7 (TOE1)
• Precocious puberty, central, 1 (KISS1R)
• Proud syndrome (ARX)
• Pseudohermaphroditism, male, with gynecomastia (HSD17B3)
• Pseudovaginal perineoscrotal hypospadias (SRD5A2)
• Robinow syndrome, AD 1 (WNT5A)
• Robinow syndrome, AR (ROR2)
• SERKAL syndrome (WNT4)
• Schinzel-Giedion midface retraction syndrome (SETBP1)
• Short-rib thoracic dysplasia 6 with/-out polydactyly (NEK1)
• Smith-Lemli-Opitz syndrome (DHCR7)
• Sudden infant death with dysgenesis of the testes syndrome (TSPYL1)
• Testicular anomalies with or without congenital heart disease (GATA4)
• Townes-Brocks syndrome 1 (SALL1)
• Waardenburg syndrome, type 2E, with/-out neurologic involvement (SOX10)
• Waardenburg syndrome, type 4C (SOX10)
• Woodhouse-Sakati syndrome (DCAF17)