CASE
The proband was a 27-year-old primigravida who was referred to the
Maternal Fetal Medicine clinic (MFM) given a personal history of obesity
and chronic renal disease post-transplant. She was seen at 16 weeks and
1 day gestation with findings of severe oligohydramnios on a viability
US. (Figure 1-A ). A limited survey of the anatomy was attempted
during which the bladder and fetal kidneys were not well visualized due
to the low amniotic fluid, large maternal body habitus, and the early
gestational age. The patient denied any symptoms of vaginal fluid loss
and had no known exposure to teratogens or any relevant medications
(e.g. NSAIDs or ACE inhibitors).
The patient’s medical history was remarkable as she was personally
induced near term, given early prenatal history of anhydramnios that
“normalized” as reported by her mother. She was subsequently diagnosed
with a solitary dysplastic left kidney. She had a right ureteropelvic
junction (UPJ) obstruction and a progressive segmental sclerosis,
leading to end-stage renal disease at 20 years of age. As such, she
required a kidney transplant the year prior to this pregnancy.
A three-generation pedigree was reviewed. Our patient was the second
child born to non-consanguineous couple of Irish and French-Canadian
descent. Her older sibling had 3 healthy children and terminated a
pregnancy with an isolated hypoplastic left heart. Her partner is one of
three healthy siblings of English and Dutch background.
A follow-up with the multi-disciplinary clinic (MFM, NICU and Genetics)
was planned with a repeat US performed at 18+5 weeks gestation, again
showing severe oligohydramnios with a maximum vertical pocket of 1.1 cm.
The bladder was visualized, but the kidneys and renal arteries were not
clearly seen. There were no anomalies identified in that US and growth
was found to be adequate for the given gestational age. The couple was
counselled by the team on the likely poor perinatal prognosis given the
severe oligohydramnios in the mid-trimester and its association with
pulmonary hypoplasia. Prenatal investigation options were discussed, and
a pregnancy termination option was presented with early induction,
postnatal autopsy, and testing. The couple opted for expected management
and was well aware of the high likelihood of poor perinatal outcomes and
the need for close follow-up.
The fetal kidney and renal artery were seen in a repeat US at 21 weeks
gestation and appeared grossly normal despite being on the smaller size.
Subsequent biweekly US showed gradual improvement of fluid levels.
Given her medical history and constellation of features, the patient was
offered a congenital abnormality of the kidney and urinary tract (CAKUT)
next generation sequencing panel, which revealed a pathogenic mutation
involving the PAX2 gene described as c.76dup: p. Val26Glyfs*28:
NM_003990.4. This is responsible for the clinical condition of RCS,
also described as a PAX2 -related disorder.
The timing of the results coincided with a repeat US at 36 weeks in
which amniotic fluid levels normalized (Figure 1-B ). Around
that time, our patient started experiencing abnormal vision in the
context of a headache. Recognising the ocular spectrum of RCS, this
prompted an urgent ocular assessment. Dilated fundus exam of both eyes
revealed no retinal tears or detachments. No ocular coloboma was
observed; however, there was vitreous syneresis and dilated vessels in
the right eye. Ocular follow-up was recommended, given the RCS diagnosis
and risk for future eye concerns. Knowing RCS’s autosomal dominant
inheritance, that diagnosis was suspected for the baby. Postnatal kidney
US and eye exam were planned for the newborn, in addition to targeted
testing for the PAX2 variant.
The amniotic fluid levels had normalized in the beginning of the third
trimester and remained in a similar range up to the time of delivery.
The patient was induced at 37 weeks and 2 days gestation and had a baby
girl weighing 7 pounds 11 ounces via an emergent caesarean-section. The
baby’s eye examination was normal. Her bloodwork showed slightly
elevated serum creatinine, partially reflecting maternal serum
creatinine, age-appropriate estimated glomerular filtration rate, some
albuminuria, and no concern about hypertension or pulmonary hypoplasia.
Her kidneys were normal in morphology on US, with a lower end of
measurement for her age. Genetic testing confirmed the maternalPAX2 variant. Upon a recent check-up, the almost 2-year-old girl
had stable mild albuminuria with echogenic kidneys based on US, with
suspected bilateral renal dysplasia, and continues to be monitored by
nephrology.