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Pain Management 2019 & Internal Medicine 2019
International Journal of Anesthesiology & Pain Medicine
ISSN: 2471-982X
Page 57
JOINT EVENT
7
th
Edition of International Conference on
Pain Management
8
th
Edition of International Conference on
Internal Medicine &
Patient Care
&
March 25-26, 2019
Rome, Italy
Int J Anesth Pain Med 2019, Volume 5
DOI: 10.21767/2471-982X-C1-006
Titin truncating mutation causing familial dilated
cardiomyopathy
Nikhila Kethireddy
1
, Christian Mosenbach
1
and
John Travis Hinson
2
1
UConn Internal Medicine Residency, USA
2
UConn Health, USA
Introduction
: Dilated Cardiomyopathy (DCM) is the third
most common cause of heart failure among adults. The
dilation of heart chambers leads to systolic dysfunction,
hence the inability tomeet the body’smetabolic demands.
Familial DCM accounts for 20% of all DCM and is due to
Titin (TTN) gene mutations leading to an abnormally
truncated Titin protein. Early identification of risk factors
and meticulous inquiry regarding family history can lead
to earlier identification of themutation and diagnosiswith
prompt treatment.
Case Report:
A 56 year old male, with an extensive
family history of cardiovascular disease, presented with
shortness of breath and palpitations. Exercise stress
test showed grossly abnormal findings which warranted
a transthoracic echocardiogram (TTE) and coronary
angiography. TTE depicted mild cardiomyopathy with an
ejectionfraction(EF)of50-55%andcoronaryangiography
showed no coronary artery disease. Hewas subsequently
started on Lisinopril and Carvedilol. Approximately 7
years later he presented with progressive shortness of
breath and wheezing at an annual checkup. A repeat TTE,
showed progression of his cardiomyopathy with EF of 35-
40%and diffuse hypokinesis. An implantable cardioverter
defibrillator was placed for primary prevention and
genetic testing/counselling was discussed. He tested
positive as a heterozygous carrier for a mutation that
truncates the Titin protein at amino acid 18,386 leading
to a frameshift mutation and a shortened protein. The
patient was advised that each of his children would
have a 50% chance of inheriting the at risk allele. After
thorough discussion he decided to have his two children
tested, the results of which are still pending.
Discussion:
Familial DCM shows an autosomal
dominant inheritance, and is genetically heterogeneous.
It is estimated that the frequency of TTN truncations
affecting the general population is 0.36% and prevalence
of frameshift mutations in the A band region is 0.057%.
Titin, one of the largest proteins in the body is a crucial
component of the cardiac myocyte. Abnormal Titin
protein leads to defective contraction of heart muscle
leading to heart failure. This case highlights a rare cause
of heart failure with reduced ejection fraction, which
should be included in the differential diagnosis of all
patient’s with a non-ischemic cardiomyopathy.
kethireddy@uchc.edu