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Gastrointestinal Oncology Case Report
Lynch Syndrome and Long QT Syndrome –
As If One Syndrome is Not Already Enough
Ju Yee Lim, 1 Barry Newell, 2 Vivienne A Ezzat 3 and Jens Samol 4
1. Medical Student, St George’s University, London, UK; 2. Consultant Pathologist, Department of Medical Oncology and Department of Pathology,
St George’s Hospital, London, UK; 3. Specialist Registrar in Cardiology, The Heart Hospital, University College London Hospitals, London, UK;
4. Consultant Medical Oncologist, St George’s University, London, UK
Abstract A 51-year-old patient was treated with chemotherapy for two synchronous colon cancers and was diagnosed with Lynch syndrome. The
patient also suffered a cardiac arrest and was also diagnosed with a long QT syndrome (LQTS) subsequently. This is the first case of a
co-existence of Lynch syndrome and LQTS.
Keywords HNPCC, Lynch syndrome, LQTS, chemotherapy, cardiac toxicity, chemoprevention
Disclosure: Ju Yee Lim, Barry Newell, Vivienne A Ezzat and Jens Samol have no conflicts of interest to declare. No funding was received for the publication of this article.
Received: 15 April 2014 Accepted: 20 June 2014 Citation: European Oncology & Haematology, 2014;10(1):25–7
Correspondence: Jens Samol, Department of Medical Oncology and Department of Pathology, St George’s Hospital, Blackshaw Rd, London SW17 0QT, UK.
A young patient was diagnosed with two synchronous colon cancers
and found to be a MLH1 carrier diagnosing him with hereditary non-
polyposis colorectal cancer (HNPCC or Lynch syndrome). Our patient
suffered a cardiac arrest while on chemotherapy (capecitabine) and
following cardiac investigations was found to have a long QT syndrome
(LQTS) as well. There is no known link between these two conditions,
but managing a patient with HNPCC and LQTS poses challenges.
A 51-year-old male presented with a change in his bowel habit and
was shown to have iron deficiency anaemia without blood in his stool.
There was no family history of cancer, he was not on any medications
and had no allergies. Of note was a history of faints. An initial diagnosis
of irritable bowel syndrome (IBS) was made and iron supplementation
was prescribed. However with no improvement in symptoms, the
patient was referred to gastroenterology for colonoscopy and the
descending colon biopsy showed an adenocarcinoma. A pre-surgical
electrocardiogram (ECG) was normal with a corrected QT (QTc) of 385
(see Figure 1). He underwent a subtotal colectomy and a diagnosis
of two synchronous Dukes’ stage C (caecum and descending colon)
cancers was made. Immunohistochemical (IHC) stains demonstrated a
loss of staining for MLH1 and PMS2 in both cancers (see Figures 2a and
2b). Subsequent genetic testing has shown him to be a MLH1 mutation
carrier. Following his surgery, the patient received four cycles of adjuvant
chemotherapy with oral capecitabine (1,000 mg/m 2 ) and intravenous
oxaliplatin (130 mg/m 2 ), called XELOX. XELOX-chemotherapy is
delivered as a 3-weekly cycle with oxaliplatin administered on the first
day of each cycle and oral capecitabine is taken twice daily for 2 weeks.
Our patient tolerated XELOX-chemotherapy well and had no dose
reductions. While taking capecitabine tablets as part of the fourth cycle,
he unfortunately suffered a cardiac arrest in a public place, but was
© TO U CH MED I CA L MED IA 2014
successfully resuscitated on site. Subsequent cardiac investigations
including an adrenaline stress test using the Mayo protocol 1 have led
to the diagnosis of LQTS (see Figures 3a and b). Genetic analysis of the
most commonly implicated genes, LQT genes 1–5, was negative but this
does not exclude the presence of a less common LQT syndrome. One
of our patient’s children was also found to have a positive adrenaline
stress test and has been started on β-blockers. This strengthens the
likelihood of an underlying genetic cause for the LQT syndrome. It was
thought that the chemotherapy tablet capecitabine and/or the metic
domperidome, given over 5 days at the beginning of each cycle at a
dose of 20 mg three times per day, led to an unmasking of the thus
far undiagnosed LQTS. Subsequently an implantable cardioverter-
defibrillator was inserted and adjuvant chemotherapy was stopped.
He has undergone genetic counselling for the inherited disorders and
continued to attend oncological follow-up. He is now 2 years post the
cardiac arrest, clinically well with a performance status of 0, and has no
evidence of a cancer associated with HNPCC.
Hereditary Non-polyposis Colorectal Cancer
HNPCC, also known as Lynch syndrome, is an autosomal dominant
inherited disorder that gives mutation carriers a high penetrance of
colorectal cancer (approximately 80 %). 2 The causative mutation
is in one of the DNA mismatch repair (MMR) genes 3 resulting in
microsatellite instability. 4 An accumulation of DNA errors occurs in cells
which contribute to tumorigenesis. 3
HNPCC accounts for around 5 % of colorectal cancers, 4 and its
prevalence in the general population is similar to that of BRCA1 and
BRCA2 mutations. 5 Patients with HNPCC usually present with colorectal
cancer at a younger age (below 50 years) and the cancer tends to occur
in the proximal colon. 6 The risk of extracolonic tumours is increased. 3