IllnessPrenatal DSD, differential diagnosis

NGS +

[Sanger]

DSD are rarely present prenatally, very complex conditions, management should be directed by highly specialised teams to allow consideration of all aspects of diagnosis, treatment + ethical issues. Female fetus (clitoromegaly with normal labia). Male fetus (micropenis, hypospadias, undescended testes, bifid scrotum). Associated abnormalities: Chromosomal, mainly trisomy 13, triploidy, 13q syndrome, in a few cases. The condition is commonly associated with genetic syndromes (Smith-Lemli-Opitz + WAGR syndromes), other defects, mainly facial clefts + cardiac defects are often found.

• 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)