Diagnostic ultrasound ( PDFDrive )

1350 PART IV Obstetric and Fetal Sonography
ARPKD is caused by mutation in the PKHD1 gene, which has
been mapped to chromosome 6p12, allowing prenatal genetic
diagnosis in at-risk families. 90,91
Autosomal Dominant Polycystic Kidney Disease
ADPKD is the most common of the hereditary renal cystic
diseases, with an incidence of 1 : 1000 in the general population.
Although this was previously termed “adult polycystic kidney
disease,” the presentation can be in the prenatal period or in
childhood; thus the preferred term is “autosomal dominant
polycystic kidney disease.” It is characterized by cyst formation
in the kidneys and liver. Cysts may also be present in the pancreas
and spleen, and the disorder is associated with CNS aneurysms.
In the early stage of the disease, only a small percentage of
nephrons show cystic dilation. In the established adult disease,
the kidneys are enlarged and contain multiple cysts of varying
sizes.
ADPKD is usually not detected prenatally because the fetal
kidneys typically appear normal. In rare cases, ADPKD can
manifest during the fetal or neonatal period with symmetrical
moderately enlarged hyperechoic kidneys, within which small
cysts (<7 mm) may be identiied (Fig. 39.18). 92,93 he bladder is
usually present, and AFV is oten normal. In contrast to ARPKD,
in which corticomedullary diferentiation is absent, 86 increased
corticomedullary diferentiation has been reported in ADPKD.
In a series of 27 cases of abnormal-appearing kidneys on prenatal
ultrasound and inal diagnosis of ADPKD (note that this is a
biased population because the kidneys appeared abnormal
prenatally), 20 had increased corticomedullary diferentiation,
six had absent or decreased corticomedullary diferentiation;
and 1 had normal corticomedullary diferentiation. 93 Because
the kidneys may appear normal in the second trimester, follow-up
scans are necessary in fetuses at risk for ADPKD.
A family history of ADPKD is critical in making the diagnosis
of ADPKD in the fetus. Because the disease is autosomal
FIG. 39.18 Autosomal Dominant Polycystic Kidney Disease. Coronal
scan of 30-week fetus shows enlarged kidneys (calipers), measuring
5 cm in length (>3 SD), with increased corticomedullary differentiation
due to increased echogenicity of the cortex.
dominant, the recurrence risk is 50%. However, it has been
reported that over 50% of the afected parents were not aware
of their disease at the time of obstetric ultrasound. 92,93 herefore
ultrasound of the parents’ kidneys is helpful in establishing the
cause. Two ADPKD causative genes have been identiied: PKD1
(located on chromosome 16p13) and PKD2 (located on chromosome
4q21). 94 Hence, prenatal genetic diagnosis is possible.
Afected families with early-onset disease in their ofspring have
a high recurrence risk for fetal presentation in subsequent afected
pregnancies. 69
he long-term prognosis for the fetus with ADPKD diagnosed
by ultrasound is still not well known because of limited data on
postnatal renal evolution and short duration of follow-up. Initial
reports suggested that although the majority of ADPKD infants
survive, they tend to have earlier onset and more signiicant
hypertension and a more rapid decline in renal function than
their afected adult relatives. 90,95,96 More recent studies reported
a favorable prognosis in most children with prenatally diagnosed
ADPKD. 97,98 In a study of 26 consecutive children with prenatal
ADPKD (excluding three terminations of pregnancy with very
large kidneys and anhydramnios), Boyer and colleagues reported
favorable prognosis in infancy and childhood, with 19 (73%)
children asymptomatic, 5 (19%) with hypertension, and 2 (8%)
with chronic renal insuiciency (mean duration of follow-up,
76 months; range, 0.5-262 months). 97 In another study of 42
patients with prenatal ADPKD, there were four terminations of
pregnancy, and among 35 patients with known serum creatinine
(age of patients at last follow-up ranged from 1 month to 20
years), renal function was abnormal in only 2. 98
Syndromes Associated With Renal Cystic Disease
Approximately 30% of fetuses with trisomy 13 have echogenic/
cystic kidneys. Other genetic conditions associated with renal
cystic disease include single-gene disorders categorized as ciliopathies
(disorders caused by mutations in genes with products
that localize to the cilium-centrosome complex). hese include
Bardet-Biedl syndrome, hepatocyte nuclear factor 1β–related
disease, Joubert syndrome, and Meckel syndrome. he phenotypes
due to the altered proteins vary from cystic kidney disease
and blindness to neurologic phenotypes, obesity, and diabetes.
HNF1β is a transcription factor that is critical for the development
of kidney and pancreas. Mutations in the HNF1β/TCF2
gene result in various phenotypes that include renal cysts and
diabetes. HNF1β mutations are oten found in fetuses with severe
renal anomalies. 79,99,100 In a retrospective study of 377 patients
with various congenital renal anomalies, the prevalence of HNF1β
mutation was (20%). 79 Among 56 patients who carried HNF1β
mutation and who had prenatal sonography, various renal
phenotypes were observed. he most common (seen in 34 of 56
fetuses) was isolated bilateral hyperechogenic kidneys, normal
in size or slightly enlarged (size ≤ +3 SD). 79 Other, less frequent
renal abnormalities were bilateral MCDK (in 2), unilateral MCDK
(in 8), and unilateral renal agenesis or hypoplasia (in 5).
HNF1β mutations follow an autosomal dominant mode of
inheritance. However, when the family history is evaluated, one
has to keep in mind incomplete penetrance and considerable
interfamilial and intrafamilial phenotypic variability, as well as