Introduction
Physiology
Pathophysiology
Clinical presentation
Incomplete masculinization in males
Female virilization
Salt-wasting
Hypoglycemia
Diagnosis
ACTH stimulation test and hormonal profiles
Neonates with ambiguous genitalia | ≥378 nmol/L |
Tanner stage I children with ambiguous genitalia | ≥165 nmol/L |
Children with premature pubarche | ≥294 nmol/L |
Adults | ≥289 nmol/L |
Molecular analysis and genetic studies
Mutation/genotype | Sex | Clinical presentation | Comments | First author [reference] |
---|---|---|---|---|
Homozygous mutation c.73G >T(p.E25X) | Female | SW Mild virilization | Huang [61] | |
(L205P, p.Leu205Pro) | Male | SW Hyperpigmentation Severe hypospadias Bifid scrotum | No detectable 3βHSD activity | Moisan [16] |
Compound heterogeneous mutation 186/insC/187 and (Y253N, p.Tyr253Asn) | Male | SW Severe undervirilization Hypospadia | Frames shift, missense No detectable 3βHSD activity | |
Compound heterogeneous mutation: W171X/(E142K, p.Glu142Lys) | Male | SW Severe undervirilization Hypospadia | Nonsense, missense No detectable 3βHSD activity | |
(A82P, p.Ala82Pro) | Male | SW Perineal hypospadias | Rabbani [60] | |
Homozygous mutation 687del27 | Male | Neonatal SW Micropenis with a perineal hypospadias | Achieved normal puberty Adult spermatic characteristics were normal | Donadille [10] |
687del27 homozygous mutation | Male | Perineal hypospadias Miropenis SW | No detectable 3βHSD activity | Moisan [16] |
Homozygous c.687del27 | Male | Severe undervirilization Low steroid production Arrested spermatogenesis Gynecomastia | Burckhardt [20] | |
Compound heterogeneous mutation 318 [ACA (Thr)] —>AA 273 [AAA(Lys) —>A] | Female | SW Sexual ambiguity | Zhang [30] | |
(T259M, p.Thr259Met) | Male | Perineal hypospadia Bifid scrotum SW | No detectable 3βHSD activity | Moisan [16] |
Female | Mild clitromegaly Premature pubarche | Marui [35] | ||
(T259R, p.Thr259Arg) | Male | Pigmentation Hypospadias Bifid scrotum SW | No detectable 3βHSD activity | Moisan [16] |
Female | Normal genitalia with severe pigmentation SW | |||
Compound heterozygote A82D, W230X | Female | Hypoglycemia SW | Nordenstrom [31] | |
(P222Q, p.Pro222Gln) | Male | Perineal hypospadias Micropenis SW | No detectable 3βHSD activity | Moisan [16] |
(P155L, p.Pro155Leu) | Male | Perineal hypospadias SW | No detectable 3βHSD activity | Moisan [16] |
Homozygous p.W355R (c.763 T>C) | Male | Hypospadias cryptorchidism Bifid scrotum SW | TART | Guven [63] |
(A10E, p.Ala10Glu) | Male | Sexual ambiguity SW Azoospermia | Missense | Alos [15] |
Female | Normal genitalia SW/normal puberty | |||
Homozygous p.Q334X (c.1000C>T) | Male | SW Hypospadias, small phallus, bifid scrotae, palpable gonads | TART | Alswailem [28] |
Female | SW Normal genitalia | |||
p.R335X (c.1003C>T) | Male | SW Hypospadias Bifid scrota Palpable gonads Advanced bone maturation | Bilateral TARTs | |
Female | SW Normal genitalia | |||
W171X :Trp171 Stop | Female | SW Normal external genitilia Failure of breast development | Nonsense | Rheaume [11] |
Compound heterogenous mutation W171X: Trp171 Stop and 186/insC/187 | Male | SW Hypospadias | Nonsense Adequate spermatogenesis | Rheaume [11] |
273ΔAA | Male | SW Ambiguous genitalia | Frameshift mutation No residual enzymatic activity | Simard [48] |
Compound heterogenous mutation (L108W, p.Leu108Trp) (P186L, p.Pro186Leu) | Male | SW Hypospadias | Missense Less than 0.5% enzymatic activity | Sanchez [53] |
(G15D, p.Gly15Asp) | Male | SW Hypospadias | Missense | Rheaume [49] |
Compound heterozygous for T181I1 and 1105delA | Female | SW Premature pubarche, slight growth acceleration, and advanced bone age | Frameshift | Johannsen [37] |
(P222T, p.Pro222Thr) | Female | SW | Missense | Pang [58] |
(P341L, p.Pro341Leu) | Male | SW Micropenis | Welzel [59] | |
Heterozygosity.244G>A (p.Ala82Thr), 931C>T(p.Gln311*) | Female | Ambiguous genitalia | Teasdale [64] | |
(S213G, p.Ser213Gly) | Female | Premature pubarche at 4 y Growth acceleration | Detectable activity | Moisan [16] |
(A245P, p.Ala245Pro) | Male | Sexual ambiguity | Detectable activity | |
(A10V, p.Ala10Val) | Male | Perinoscrotal hypospadia | Detectable activity (30%) | Moisan [16] |
(L236S, p.Leu236Ser) | Male | Perinoscrota hypospadias Micropenis | Missense | Moisan [16] |
Female | Premature pubarche | Missense | Nayak [57] | |
(A245):Ala245Pro | Male | Hypospadias Bifid scrotum | Missense Detectable enzymatic activity | Simard [24] |
(G129R, p.Gly129Arg) | Male | Perineal hypospadias | Missense/splice Detectable enzymatic activity | Rheaume [51] |
Female | Normal genitalia Premature pubarche | |||
(N100S, p.Asn100Ser) | Male | Perineal hypospadias | Missense | Mebarki [55] |
(Y254D, p.Tyr254Asp) | Female | Severe acne Primary amenorrhea Clitoromegaly Moderate hirsutism | Missense | Sanchez [54] |
(L173R, p.Leu173Arg) | Male | Perineal hypospadias | Missense Raised as female | Russel [52] |
(A82T, p.Ala82Thr) | Female | Some with no signs of CAH One patient with premature pubarche | Missense | Mendonca [50] |
Male | Perineal hypospadias | |||
p.G250V | Female | Precocious pubarche Postnatal clitoromegaly | Baquedano [62] | |
(A167V, p.Ala167Val) | Female | Premature pubarche | Missense | Moisan [16] |
(K216E, p.Lys216Glu) | Female | Premature pubarche | Missense | Moisan [16] |
(P22H, p.Pro221His) | Female | Premature pubarche | Moisan [16] | |
(G294V, p.Gly294Val) | Male | Hypospadias | Moisan [16] |