FM OCTOBER 2018 ISSUE - digital edition

diagnositcs
LOST IN TRANSLATION
Microdeletion syndrome is one of a frequently unsuspected group
of disorders in prenatal evaluation
DR PRIYA KADAM
Thirty nine-year-old Juhi was
cautiously delighted when she
learned she was pregnant again.
She had previously miscarried a foetus
affected with Down Syndrome. During
her current pregnancy, she consulted
a geneticist who suggested a test
for Down Syndrome and a group
of disorders called microdeletion
syndromes. She opted for the test as it
was non-invasive and accurate. Sadly,
this time, the foetus was diagnosed with
another disorder - 22q11.2 microdeletion
syndrome. Though devastated, Juhi
appreciated the information she
received early in pregnancy, and
accordingly made an informed decision.
Such information is vital to expectant
parents for thought-through early
pregnancy decisions and to avoid
the distress caused by the birth of an
abnormal baby unexpectedly.
Down Syndrome, with an incidence
rate of 1 in 800 pregnancies, is the most
common genetic/chromosomal disorder
and is reasonably known to both the
medical fraternity and the general
public. From the 1960s, there have been
continuously improving approaches
to screen for and diagnose this and a
few other significant conditions during
pregnancy, given the seriousness of
these conditions. However, there is
another group of clinically relevant
disorders caused by the deletion (loss)
of a small part of a chromosome,
called microdeletion syndromes. This
chromosomal loss occurs very early
during development and is irreversible.
Microdeletion syndromes are clinically
important as they are associated
with intellectual impairment, learning
difficulties, autism and a host of other
abnormalities, including those related to
the heart and the kidneys. The reported
incidence of microdeletion syndromes is
1 in 1000 pregnancies. These conditions
are not easy to detect during pregnancy.
They were also previously considered
rare and therefore not high-priority
candidates for screening programmes.
Most individuals were/are identified after
birth, during childhood or even during
adulthood.
Unravelling DiGeorge
Initially, microdeletion syndromes
were described when patients
with a cluster of specific features
(phenotype) were observed together.
The genetic basis of these conditions
began to be identified around 30
CAUSED BY A DELETION IN
A SMALL AND VARIABLE
PART OF CHROMOSOME
22, 22Q11.2 DELETION
SYNDROME HAS AN
INCIDENCE OF 1 IN EVERY
2000 BIRTHS.
years ago, with the development of
techniques such as fluorescent in situ
hybridization. With the development
of other advanced techniques such
as chromosomal microarrays, more
and more areas of such repeated and
specific chromosomal losses began to
be identified, which correlated clinically
observed syndromes.
22q11.2 deletion syndrome
is commonly known as DiGeorge
syndrome. Velocardiofacial syndrome
and conotruncal anomaly face
syndrome are the most commonly
used names for the microdeletion
syndrome. It is the second biggest
cause of congenital heart disease and
developmental delays. Caused by a
deletion in a small and variable part of
chromosome 22, it has an incidence of
1 in every 2000 births. The syndrome
is associated with heart defects, cleft
palate, developmental delay, mental
and psychiatric disorders, endocrine
disorders, distinct facial features
and low calcium levels among other
features. The condition is associated
with premature mortality, based on the
severity of individual features. There
is no cure and the best management
strategy is a multidisciplinary approach
aimed at handling individual symptoms.
Early management of symptoms greatly
improves outcome. Most of the cases
occur spontaneously without family
history, while in 5-10% of the cases, it is
inherited with 50% risk of transmitting
the disorder. This risk of carrying an
affected pregnancy with microdeletion
syndrome is not related to maternal
age and the risk remains the same
throughout a women’s reproductive
period.
The syndrome was clinically
described in English language in
1960s in children who presented
with the triad of immunodeficiency,
hypoparathyroidism and congenital
heart disease. However, there is a huge
variability in the presentation and the
age of recognition of symptoms. Though
common, the lack of awareness of the
condition and/or testing methods and
the huge variability in presentation
delay diagnosis. The typical age of
molecular diagnosis is around five
years after numerous visits to different
clinical specialties. Early identification
and management is useful to improve
the quality of life. Though the condition
can be suspected during pregnancy
28 / FUTURE MEDICINE / OCTOBER 2018