Date: June 15, 2013

Genetic consultation – Andrei Gabriela.

The couple was referred to a genetic counseling due to the history of

their previous pregnancy.
Gabriela Andrei, 26 y old, her husband, 36 y old. Both are healthy, not
consanguineous.
There is no family history of birth defects, known genetic diseases,
miscarriages, besides a history of the woman’s sister who died at the
age of 3 y, from unknown reason.

The previous pregnancy in 2012 was spontaneous. During the first

trimester of pregnancy Gabriela had bleeding and hematoma was
observed.
The first trimester biochemical screening was normal, so as US scan
at 16th week of gestation.
Later in pregnancy the fetus was big for gestational age, and
oligohydramnios was observed. No additional details were provided.
The baby was born by c/s at 36th week of gestation with weight 3400
gr, The boy died two hours after birth.
These are the clinical signs mentioned in the medical record:
cardiorespiratory stress, global cardiac insufficiency, global cardiac
hypertrophy.
In addition, meningo cerebral edema, cardiomegaly with right and left
ventricular hypertrophy, hepatomegaly, splenomegaly, intestinal
hypoplasia, bilateral polycystic kidneys.

Thrombophilia examinations performed to Gabriela were normal.

Evaluation:

According to the data provided, differential genetic diagnosis seems

to be broad.
The following options could be more relevant:

 infantile polycystic kidney disease, with autosomal recessive

inheritance, meaning that both parents are carriers of a
disease causing gene PKHD1. In this case the recurrent risk in
every pregnancy is 25% both for boys and girls.
  autosomal dominant polycystic kidney disease, then the
recurrent risk could reach 50% in every pregnancy if one of the
parents has kidney cysts or carries a mutated gene.

 an overgrowth syndrome (less probably) as Simpson GolabI

syndrome, with X linked inheritance, meaning that a healthy
mother , who is a carrier of a disease causing gene CPC3 or
CPC4, can transmit a disease mostly to her sons. In such case
the recurrence risk can reach 50% in every pregnancy with a
male fetus.

But could be some other autosomal dominant or autosomal

recessive syndromes.

 a chromosomal anomaly, then the recurrent risk may be in

spectrum from 1-2% to 30 %.

 a de novo mutation, then a recurrence risk is low.

In an attempt to reach a correct diagnosis, it is important to perform a

number of tests before planning another pregnancy. If the genetic
basis of the disease will be identified, it could be possible to offer a
reliable prenatal diagnosis in future pregnancies at 11-12 weeks in
CVS or at 17-18 weeks in amniocentesis.
Usually we prefer to make an appropriate genetic investigation on the
child's DNA sample, but unfortunately, no DNA sample was kept, so
we can offer some tests for the parents.

If we wouldn’t be able to find out an exact genetic diagnosis, it’s

recommended to perform in every future pregnancy US scans
directed on size and echogenicity of kidneys ,fetal growth and
movements, the amount of amniotic fluid, diaphragm, hands and feet,
including fingers, the size and structure of heart, liver, brain
structure, signs of hydrops fetalis.
It’s very important to refer to a clinical geneticist with any abnormal
sign during the pregnancy.
Recommendations:

1. Karyotype test in blood for both parents to rule out a familial

chromosomal abnormality.

2. US scan of kidneys for both parents to rule out familial autosomal

dominant polycystic kidney disease.

3. Clinical examination of both parents by medical geneticist, in

question of macrosomia, dysmorphic features, skeletal signs.

4. Sequencing of PKHD1 in both parents.

5. X inactivation test in blood for Gabriela.

6. In case of skewed x inactivation, sequencing of CPC3 and CPC4

genes could be suggested, and according these results MLPA testing
of both genes may be done
.
7. Obtain information regarding a cause of death of Gabriela’s sister.

8. Another genetic counseling with the results, preferably before

planning additional pregnancy.

9. If no genetic cause of clinical signs in the first son would be found,

detailed fetal US scans are recommended at 15, 24, 28, 32 weeks of
gestation, as well as nuchal translucency at 11-12 weeks and
biochemical serum screening in first and second trimester.

10. Genetic counseling is recommended in every additional

pregnancy to get instructions for appropriate observation and tests.
The couple could decide to perform an amniocentesis for regular
karyotype and CMA testing.

11. Gabriela should take a folic acid before planning every pregnancy
and during a first trimester.

12. Blood test for testing a carrier status of some common genetic
diseases is recommended for the mother before planning another
pregnancy.
13. Genetic counseling is recommended to family members, planning
a pregnancy.

Please, do not hesitate to contact us with any further questions.

Sincerely,
Bella Davidov,
Genetic Counselor