ultrasound diagnosis of fatal anomalies

GENITAL ANOMALIES
Table 7.1
Heterogeneous genital anomalies arising from various causes
Chromosomal aberrations
Xp, 1 p, 4 p, 9 p duplication;
10q deletion; trisomy 13;
17 q aberration; triploidy;
gonosomal mosaic
(e.g., 45, X/6, XY)
Xp duplication: rare chromosomal aberration, genital anomalies of Y,
double Xp chromosome: normal female genitalia or intersexual genitalia
Genetic mutations
Adrenogenital syndrome (AGS)
Testicular feminization
XY gonadal dysgenesis
Pure hermaphroditism
Smith–Lemli–Opitz syndrome,
type II
Aarskog syndrome
Genitopalatocardiac syndrome
Hypospadias
Denys–Drash syndrome
Combined chromosomal aberration and molecular defect
XX man
Camptomelic dysplasia
Multifactorial inheritance
Hypospadias
Nongenetic causes
Vanishing twin
Autosomal-recessive; the most common causes (in 70%) are mutations
in the CYP21 gene for 21-hydroxylase, gene locus 6 p21
Frequently X-recessive, gene mutation in the androgen receptor located
at Xq11 – 12; any form between normal female genitals to intersexuality
if 46,XY karyotype present
Genetically heterogeneous; a frequent cause, in 10–15% of test persons,
is a gene mutation in the testes-determining factor gene (SRY
gene); a further 10–15% show deletion of the SRY gene, gene locus:
Yp11.3. Depending on the expression of the gene mutation, there is
either pure XY gonadal agenesis (Swyer syndrome) with normal female
genitalia, or intersexual genitalia in incomplete gonadal dysgenesis.
X-related recessive inheritance has been reported; autosomal-recessive
inheritance with limited genital development is probable
Possible combination of chromosomes: 46,XX, 46,XY or 46,XX/46,XY.
Genetic cause largely unknown; SRY mutations have been seen in some
cases, ovotestes or ovaries and testicles are present, external genitalia
normal male or intersexual, presence of breasts
Autosomal-recessive; hypospadias and cryptorchism if XY, no genital
anomalies in female patients
X-related recessive, hypospadias
Hypospadias or female genitalia in 46,XY karyotype, cardiac anomalies,
cleft palate, clubfeet, kyphoscoliosis
In rare cases, mutation in the SRY gene; mostly multifactorial inheritance
(see below)
Gonadal dysgenesis; in 46,XY karyotype female or intersexual genitals,
renal malformations, mutations in the Wilms tumor-1 gene (WT1)
Normal female chromosomes. The gene for testes-determining factor
(SRY gene) is incorrectly located on an X chromosome, a crossover that
has failed in the germ-cell phase—this is the cause in 70% of XX men;
the etiology for the rest is unclear. Normal male genitals are present
Two-thirds of patients have genital malformations with autosomaldominant
inheritance
If hypospadias is not associated with a syndrome, the recurrence rate
for male siblings is 10%
Early intrauterine death of a twin, with residual cellular components.
This may be responsible for discrepancies in genital findings (especially
in CVS diagnosis) that cannot be explained by contamination by maternal
cells
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