Incidental Findings

Arcensus sequences your entire DNA, however the entire genome is not interpreted. We analyse:

  • the genes that are included in the genetic sequencing product you have selected and
  • the genes that belong to the incidental findings – in the case you have consented to do so. 

The phrase “incidental findings” has a special definition; we call “incidental findings” those results that are not related to the reason (indication) why you have ordered the sequencing. “Incidental findings”, however, are potentially causing a disease with – if symptoms are present or even preventively – available treatment options. Based on the recommendations of the American College of Medical Genetics (ACMG), there is a list of 73 genes that can cause 82 disorders that are considered “incidental findings”. 

Arcensus will take this ACMG list as a basis but will continuously update the list and add new genes – based on newest data and scientific insights. Independent of the product you purchased, Arcensus can inform you about the “incidental findings” if you consent it/them to be reported.

Gene
Gene OMIM#
Disease
Disease OMIM#
Key considerations
Gene

ACTA2

Gene OMIM#

102620

Disease

Familial thoracic aortic aneurysm

Disease OMIM#

611788

Key considerations

Regular assessment of the large arteries (including aorta) by sonography (MRI). Medications can slow aneurism formation. Surgery of the arteries can normalize the pathology.

Gene

ACTC1

Gene OMIM#

102540

Disease

Hypertrophic cardiomyopathy

Disease OMIM#

612098

Key considerations

Affected Individuals may be treated with a specific medication. If drug therapy does not work, a permanent pacemaker or defibrillator may be implanted. Surgery may be a treatment option in case of restricted blood flow.

Gene

ACVRL1

Gene OMIM#

601284

Disease

Hereditary hemorrhagic telangiectasia

Disease OMIM#

600376

Key considerations

“Behacizumab”, a specific new medication (anti-VEGF antibody) which has been introduced recently, targets VEGF (vascular endothelial growth factor) and the angiogenic pathway.

Gene

APC

Gene OMIM#

611731

Disease

Familial adenomatous polyposis

Disease OMIM#

175100

Key considerations

Annual colonoscopy, removal of adenomatous polyps. Bowel surgery might be considered.

Gene

APOB

Gene OMIM#

107730

Disease

Familial hyper­cholesterolemia

Disease OMIM#

144010

Key considerations

Cholesterol lowering medication (should begin as soon as possible after diagnosis). Treatment of coronary atherosclerosis may include coronary angioplasty, stents, and lifestyle modifications (e.g., smoking cessation, dietary changes, weight control, physical activity).

Gene

ATP7B

Gene OMIM#

606882

Disease

Wilson disease

Disease OMIM#

277900

Key considerations

Life-long administration of chelating agents (D-penicillamine, trientine salts) or zinc salt is recommended. Liver transplantation is under specific condition extremely helpful in cases of liver failure.

Gene

BMPR1A

Gene OMIM#

601299

Disease

Juvenile polyposis syndrome

Disease OMIM#

174900

Key considerations

Management should involve routine colonoscopy; endoscopic polypectomy is the gold standard for treatment. Due to the risk of cancer and polyposis extension, surgical colectomy (large bowel removal) may be proposed.

Gene

BRCA1

Gene OMIM#

113705

Disease

Hereditary breast and ovarian cancer

Disease OMIM#

604370

Key considerations

From the age of 25 years onwards, an annual mammography (magnetic resonance imaging), bi-annual transvaginal ultrasound, and a CA-125 antigen test are prescribed. In men: clinical breast exam from 35 years of age on, PSA test annually; in premenopausal women prophylactic bilateral mastectomy and prophylactic bilateral salpingo-oophorectomy can be considered.

Gene

BRCA2

Gene OMIM#

600185

Disease

Hereditary breast and ovarian cancer

Disease OMIM#

612555

Key considerations

From 25 years of age on, annual mammography (magnetic resonance imaging), every 6 months transvaginal ultrasound + CA-125 antigen test. In men: clinical breast exam from 35 years of age on, PSA test annually; in premenopausal women prophylactic bilateral mastectomy and prophylactic bilateral salpingo-oophorectomy can be considered.

Gene

BTD

Gene OMIM#

609019

Disease

Biotinidase deficiency

Disease OMIM#

253260

Key considerations

Supplementation with oral biotin in the free, non-protein bound, form is the primary treatment and improves symptoms in symptomatic patients, and prevents symptoms in those identified by new-born screening or before symptoms have developed.

Gene

CACNA1S

Gene OMIM#

114208

Disease

Malignant hyperthermia

Disease OMIM#

601887

Key considerations

Affected individuals have to avoid volatile anaesthetics and the depolarizing muscle relaxant.

Gene

CASQ2

Gene OMIM#

114251

Disease

Catecholaminergic polymorphic ventricular tachycardia

Disease OMIM#

611938

Key considerations

The first pharmacological line is non-selective beta-blockers without sympathomimetic activity. Flecainide is considered the first-choice addition when the effect of beta-blockers is not complete. In patients who are refractory to pharmacologic treatment, left cardiac sympathetic denervation (LCSD) can be performed. Finally, in patients who are refractory to maximal pharmacologic treatment and LCSD (or LCSD is not available) an implanted cardioverter defibrillator (ICD) is indicated.

Gene

COL3A1

Gene OMIM#

120180

Disease

Ehlers-Danlos syndrome, vascular type

Disease OMIM#

130050

Key considerations

Regular screening for hypertension and arterial disease (e.g., aortic aneurism, intracranial aneurism) by ultrasound, MRI, or CT should be conducted. The treatment includes lowering blood pressure and aortic surgery to prevent dissection and disruption of aortic aneurism.

Gene

DSC2

Gene OMIM#

125645

Disease

Arrhythmogenic right ventricular cardiomyopathy

Disease OMIM#

610476

Key considerations

Arrhythmic medications and anticoagulants are given. In patients with persistent symptomatic arrhythmias, ablation of conduction pathways may be attempted. Patients with any high risk of sudden death require insertion of an implantable cardioverter-defibrillator (ICD).

Gene

DSG2

Gene OMIM#

125671

Disease

Arrhythmogenic right ventricular cardiomyopathy

Disease OMIM#

610193

Key considerations

Primary treatment and prevention involves arrhythmic medications and anticoagulants. In patients with persistent symptomatic arrhythmias, ablation of conduction pathways may be attempted. Patients with any high risk of sadden death require insertion of an implantable defibrillator (ICD).

Gene

DSP

Gene OMIM#

125647

Disease

Arrhythmogenic right ventricular cardiomyopathy

Disease OMIM#

607450

Key considerations

Primary treatment involves arrhythmic medications and anticoagulants. In patients with persistent symptomatic arrhythmias, ablation of conduction pathways may be attempted. Patients with any high risk of sudden death require insertion of an implantable defibrillator (ICD).

Gene

DSP

Gene OMIM#

125647

Disease

Dilated cardiomyopathy

Disease OMIM#

615821

Key considerations

Affected individuals should be screened for structural and functional (e.g., arrythmia) heart abnormalities. Treatment of dilated cardiomyopathy may include a) drugs (e.g., angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers), implantable devices (e.g., biventricular pacemaker, implantable cardioverter-defibrillators)

Gene

ENG

Gene OMIM#

131195

Disease

Hereditary haemorrhagic telangiectasia

Disease OMIM#

187300

Key considerations

The therapeutic treatments for HHT were intended to reduce the symptoms of the disease. However, new drug, bevacizumab (anti-VEGF antibody), has been introduced recently that target VEGF (vascular endothelial growth factor) and the angiogenic pathway.

Gene

FBN1

Gene OMIM#

134797

Disease

Marfan syndrome

Disease OMIM#

154700

Key considerations

Management aims to limit aortic dilation (medications and a reduction in sport activities) and regularly monitor the aorta (annual echocardiograms) to allow the aortic root to be replaced before dissection occurs. Surgery can also be offered for skeletal and ocular anomalies.

Gene

FLNC

Gene OMIM#

102565

Disease

Dilated cardiomyopathy

Disease OMIM#

617047

Key considerations

Affected individuals should be screened for structural and functional (e.g., arrythmia) heart abnormalities. Treatment of dilated cardiomyopathy may include drugs (e.g., angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers), implantable devices (e.g., biventricular pacemaker, implantable cardioverter-defibrillators)

Gene

GAA

Gene OMIM#

606800

Disease

Pompe disease

Disease OMIM#

232300

Key considerations

Enzyme replacement therapy (ERT) is an approved treatment for all patients with Pompe disease. It involves the intravenous administration of recombinant human acid alpha-glucosidase (rhGAA).

Gene

GLA

Gene OMIM#

300644

Disease

Fabry disease

Disease OMIM#

301500

Key considerations

Enzyme replacement therapy (ERT) is the cornerstone for treatment of Fabry disease. Two forms of the recombinant enzyme are available: agalsidase alpha and agalsidase beta.

Gene

HFE

Gene OMIM#

613609

Disease

Hereditary hemochromatosis (c.845G>A; p.C282Y homozygotes only)

Disease OMIM#

235200

Key considerations

Treatments for hemochromatosis include therapeutic phlebotomy, iron chelation therapy, dietary changes, and treatment for complications. The goals of treating hemochromatosis include: reducing the amount of iron in your body to normal levels.

Gene

HNF1A

Gene OMIM#

142410

Disease

Maturity-Onset of Diabetes of the Young

Disease OMIM#

600496

Key considerations

MODY patients likely respond to high dose sulfonylureas (e.g., glibenclamide).

Gene

KCNH2

Gene OMIM#

152427

Disease

Long-QT syndrome type 2

Disease OMIM#

613688

Key considerations

The treatment of choice for long QT syndrome affected individuals (symptomatic and asymptomatic) is drug therapy with beta-adrenergic blocking agents. Individuals for whom beta blockers are unsuccessful or contraindicated may be treated by a surgical procedure with left cardiac sympathetic denervation. For affected individuals who have been resuscitated from cardiac arrest (whether on or off beta blockers), treatment with an implantable automatic cardioverter-defibrillator (ICD) is considered.

Gene

KCNQ1

Gene OMIM#

607542

Disease

Long-QT syndrome type 1

Disease OMIM#

192500

Key considerations

The treatment of choice for long QT syndrome affected individuals (symptomatic and asymptomatic) is drug therapy with beta-adrenergic blocking agents. Individuals for whom beta blockers are unsuccessful or contraindicated may be treated by a surgical procedure with left cardiac sympathetic denervation. For affected individuals who have been resuscitated from cardiac arrest (whether on or off beta blockers), treatment with an implantable automatic cardioverter-defibrillator (ICD) is considered.

Gene

LDLR

Gene OMIM#

606945

Disease

Familial hyper­cholesterolemia

Disease OMIM#

143890

Key considerations

Dietary changes, cholesterol lowering medication (begin as soon as possible after diagnosis). Treatment of coronary atherosclerosis may include lifestyle modification (e.g., smoking cessation, weight control, physical activity), drugs, coronary angioplasty, and stents.

Gene

LMNA

Gene OMIM#

150330

Disease

Dilated cardiomyopathy

Disease OMIM#

115200

Key considerations

Affected individuals should be screened for structural and functional (e.g., arrythmia) heart abnormalities. Treatment of dilated cardiomyopathy may include a) drugs (e.g., angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers), implantable devices (e.g., biventricular pacemaker, implantable cardioverter-defibrillators).

Gene

MAX

Gene OMIM#

154950

Disease

Hereditary paraganglioma-pheochromocytoma syndrome

Disease OMIM#

171300

Key considerations

Blood and urine analysis to detecting elevated levels of catecholamines or its metabolites should be performed. A specialized test, the clonidine suppression test, may be performed to rule out other causes of elevated catecholamines. Imaging techniques such as computed tomography (CT scan) and magnetic resonance imaging (MRI) are often performed to determine the specific location and size of a pheochromocytoma. Surgery is the main form of treatment for pheochromocytoma.

Gene

MEN1

Gene OMIM#

613733

Disease

Multiple endocrine neoplasia type 1

Disease OMIM#

131100

Key considerations

Annual life-long screening is recommended for all the carriers of a MEN1 mutations. Six-monthly screening with CT, MRI and blood biochemistry is recommended). Treatment by surgery is based on approaches for each specific tumour. Pharmacological therapies are available for treatment of hormone over-secretion and related syndromes; calcimimetic can be used to treat primary hyperparathyroidism in patients in whom surgery had either failed or was contraindicated; bone anti-resorptive agents are used to reduce hypercalcemia and limit bone resorption; dopamine agonists are used for prolactinoma; somatostatin analogs for growth hormone secreting tumours and for controlling the secretory hyperfunction.

Gene

MLH1

Gene OMIM#

120436

Disease

Lynch syndrome

Disease OMIM#

609310

Key considerations

Several medical options are available for managing cancer risks in people who have Lynch syndrome. Colonoscopies every 1-2 years starting between the ages of 20-25 (or 2-5 years before the earliest colorectal cancer in the family) are the most effective way to prevent colorectal cancer. Other available options may reduce the chance of developing cancer or improve the likelihood of detecting it earlier: aspirin use to reduce the risk of colorectal cancer; transvaginal ultrasound and endometrial biopsy every 1–2 years, beginning at age 30–35 years, to detect endometrial cancer; CA-125 blood tests every year to detect ovarian cancer; hysterectomy and bilateral salpingo-oophorectomy to prevent gynaecologic cancers; upper endoscopies every 3-5 years starting between the ages of 30-35 to detect stomach and small bowel cancer.

Gene

MSH2

Gene OMIM#

609309

Disease

Lynch syndrome

Disease OMIM#

120435

Key considerations

Several medical options are available for managing cancer risks in people who have Lynch syndrome. Colonoscopies every 1-2 years starting between the ages of 20-25 (or 2-5 years before the earliest colorectal cancer in the family) are the most effective way to prevent colorectal cancer. Other available options may reduce the chance of developing cancer or improve the likelihood of detecting it earlier: aspirin use to reduce the risk of colorectal cancer; transvaginal ultrasound and endometrial biopsy every 1–2 years, beginning at age 30–35 years, to detect endometrial cancer; CA-125 blood tests every year to detect ovarian cancer; hysterectomy and bilateral salpingo-oophorectomy to prevent gynaecologic cancers; upper endoscopies every 3-5 years starting between the ages of 30-35 to detect stomach and small bowel cancer.

Gene

MSH6

Gene OMIM#

600678

Disease

Lynch syndrome

Disease OMIM#

614350

Key considerations

Several medical options are available for managing cancer risks in people who have Lynch syndrome. Colonoscopies every 1-2 years starting between the ages of 20-25 (or 2-5 years before the earliest colorectal cancer in the family) are the most effective way to prevent colorectal cancer. Other available options may reduce the chance of developing cancer or improve the likelihood of detecting it earlier: aspirin use to reduce the risk of colorectal cancer; transvaginal ultrasound and endometrial biopsy every 1–2 years, beginning at age 30–35 years, to detect endometrial cancer; CA-125 blood tests every year to detect ovarian cancer; hysterectomy and bilateral salpingo-oophorectomy to prevent gynaecologic cancers; upper endoscopies every 3-5 years starting between the ages of 30-35 to detect stomach and small bowel cancer.

Gene

MUTYH

Gene OMIM#

604933

Disease

MUTYH-associated polyposis

Disease OMIM#

608456

Key considerations

Colonoscopy every 1 to 2 years, beginning at age 25 to 30; once a person develops polyps, the colonoscopy frequency may be increased with the goal of removing all large polyps. If an individual develops colorectal cancer or if colon polyps are too numerous to be removed during a colonoscopy, surgery may be considered.

Gene

MYBPC3

Gene OMIM#

600958

Disease

Hypertrophic cardiomyopathy

Disease OMIM#

115197

Key considerations

Affected Individuals have to be treated with drugs. If drug therapy does not work, a permanent pacemaker or defibrillator may be implanted. Surgery may be a treatment option in case of restricted blood flow.

Gene

MYH11

Gene OMIM#

160745

Disease

Familial thoracic aortic aneurysm

Disease OMIM#

132900

Key considerations

Regular assessment of the large arteries (including aorta) by sonography (MRI). Medications can slow aneurism formation. Surgery of the arteries can normalize the pathology.

Gene

MYH7

Gene OMIM#

160760

Disease

Hypertrophic cardiomyopathy

Disease OMIM#

192600

Key considerations

Affected Individuals may be treated with drugs. If drug therapy does not work, a permanent pacemaker or defibrillator may be implanted. Surgery may be a treatment option in case of restricted blood flow.

Gene

MYH7

Gene OMIM#

160760

Disease

Dilated cardiomyopathy

Disease OMIM#

613426

Key considerations

Affected individuals should be screened for structural and functional (e.g., arrythmia) heart abnormalities. Treatment of dilated cardiomyopathy may include a) drugs (e.g., angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers), implantable devices (e.g., biventricular pacemaker, implantable cardioverter-defibrillators)

Gene

MYL2

Gene OMIM#

160781

Disease

Hypertrophic cardiomyopathy

Disease OMIM#

608758

Key considerations

Affected Individuals may be treated with drugs. If drug therapy does not work, a permanent pacemaker or defibrillator may be implanted. Surgery may be a treatment option in case of restricted blood flow.

Gene

MYL3

Gene OMIM#

160790

Disease

Hypertrophic cardiomyopathy

Disease OMIM#

608751

Key considerations

Affected Individuals may be treated with drugs. If drug therapy does not work, a permanent pacemaker or defibrillator may be implanted. Surgery may be a treatment option in case of restricted blood flow.

Gene

NF2

Gene OMIM#

607379

Disease

Neurofibromatosis type 2

Disease OMIM#

101000

Key considerations

Yearly magnetic resonance imaging (MRI), beginning in the teenage years. Hearing evaluations, including audiometry and a brain stem auditory evoked response (BERA).

Gene

OTC

Gene OMIM#

300461

Disease

Ornithine transcarbamylase deficiency

Disease OMIM#

311250

Key considerations

Dietary restrictions in individuals with OTC deficiency are aimed at limiting the amount of protein intake. The sodium phenylbutyrate phenylbutyrate are used for the treatment of chronic hyperammonaemia, sodium phenylacetate and sodium benzoate are used to treat acute hyperammonaemia in affected Individuals. Individuals with OTC deficiency benefit from treatment with arginine, or its precursor citrulline, which are needed to maintain a normal rate of protein synthesis. Multiple vitamins and calcium supplements may also be used.

Gene

PALB2

Gene OMIM#

610355

Disease

Hereditary breast cancer

Disease OMIM#

114480

Key considerations

Annual mammography (magnetic resonance imaging) from 25 years.

Gene

PCSK9

Gene OMIM#

607786

Disease

Familial hyper­cholesterolemia

Disease OMIM#

603776

Key considerations

Dietary changes, cholesterol lowering medication (should begin as soon as possible after diagnosis). Treatment of coronary atherosclerosis may include lifestyle modification (e.g., smoking cessation, weight control, physical activity), drugs, coronary angioplasty, and stents.

Gene

PKP2

Gene OMIM#

602861

Disease

Arrhythmogenic right ventricular cardiomyopathy

Disease OMIM#

609040

Key considerations

Primary treatment involves arrhythmic medications and anticoagulants. In patients with persistent symptomatic arrhythmias, ablation of conduction pathways may be attempted. Patients with any high risk of sadden death require insertion of an implantable cardioverter-defibrillator (ICD). Heart failure is treated in the usual way, with diuretics, ACE inhibitors and anticoagulants, in severe cases, cardiac transplantation may be required.

Gene

PMS2

Gene OMIM#

600259

Disease

Lynch syndrome

Disease OMIM#

614337

Key considerations

Several medical options are available for managing cancer risks in people who have Lynch syndrome. Colonoscopies every 1-2 years starting between the ages of 20-25 (or 2-5 years before the earliest colorectal cancer in the family) are the most effective way to prevent colorectal cancer. Other available options may reduce the chance of developing cancer or improve the likelihood of detecting it earlier: aspirin use to reduce the risk of colorectal cancer; transvaginal ultrasound and endometrial biopsy every 1–2 years, beginning at age 30–35 years, to detect endometrial cancer; CA-125 blood tests every year to detect ovarian cancer; hysterectomy and bilateral salpingo-oophorectomy to prevent gynaecologic cancers; upper endoscopies every 3-5 years starting between the ages of 30-35 to detect stomach and small bowel cancer.

Gene

PRKAG2

Gene OMIM#

602743

Disease

Hypertrophic cardiomyopathy

Disease OMIM#

600858

Key considerations

Affected Individuals may be treated with drugs. If drug therapy does not work, a permanent pacemaker or defibrillator may be implanted. Surgery may be a treatment option in case of restricted blood flow.

Gene

PTEN

Gene OMIM#

601728

Disease

PTEN hamartoma tumour syndrome

Disease OMIM#

158350

Key considerations

Affected individuals of all ages: an annual thyroid ultrasound scan and an annual skin exam. Starting at age 30: affected women – an annual mammogram; an annual breast MRI and an annual endometrial biopsy or transvaginal ultrasound. Starting at age 40: all affected adults – a colonoscopy every 2 years, – a kidney ultrasound scan or MRI every 2 years. Preventive surgery: affected women – a prophylactic bilateral mastectomy and hysterectomy may be considered.

Gene

RB1

Gene OMIM#

614041

Disease

Retinoblastoma

Disease OMIM#

180200

Key considerations

Children need to be examined by an ophthalmologist immediately after birth. These examinations should be continued for the next 5-6 years, at least, once every 2-6 months.

Gene

RET

Gene OMIM#

164761

Disease

Familial medullary thyroid cancer

Disease OMIM#

155240

Key considerations

The thyroid gland should be surgically removed to prevent cancer from developing

Gene

RET

Gene OMIM#

164761

Disease

Multiple endocrine neoplasia type 2A

Disease OMIM#

171400

Key considerations

The thyroid gland should be surgically removed to prevent cancer from developing. For patients with moderate risk mutations, surgery can be postponed until calcitonin becomes elevated or in childhood. However, close monitoring by an experienced medical professional is important. Yearly blood tests for ionized calcium and parathyroid hormone levels, beginning in childhood, for catecholamines and catecholamine metabolites (metanephrine and normetanephrine), beginning in childhood; magnetic resonance imaging (MRI) or computerized tomography (CT or CAT) scan of the abdomen to detect pheochromocytomas, every 4 to 5 years or when abnormal catecholamine or metanephrine levels are detected.

Gene

RET

Gene OMIM#

164761

Disease

Multiple endocrine neoplasia type 2B

Disease OMIM#

162300

Key considerations

The thyroid gland should be surgically removed to prevent cancer from developing. Additional screening recommendations may include: yearly blood tests for catecholamines and catecholamine metabolites (metanephrine and normetanephrine), beginning in childhood; magnetic resonance imaging (MRI) or computerized tomography (CT or CAT) scan of the abdomen to detect pheochromocytomas, every 4 to 5 years or when abnormal catecholamine or metanephrine levels are detected.

Gene

RPE65

Gene OMIM#

180069

Disease

RPE65-related retinopathy

Disease OMIM#

204100, 613794

Key considerations

Treatment is primarily aimed at slowing progression of the disease. Vitamin A palmitate and lutein-DHA may be provided as protecting antioxidants. Oral acetazolamide or topical dorzolamide are used to reduce cystoid macular edema. Lens extraction is required when cataracts reduce visual acuity. Sunglasses with short wavelength filtering improve visual performance and optical aids are recommended.

Gene

RYR1

Gene OMIM#

180901

Disease

Malignant hyperthermia

Disease OMIM#

145600

Key considerations

Affected individuals should avoid volatile aesthetic and the depolarizing muscle relaxant.

Gene

RYR2

Gene OMIM#

180902

Disease

Catecholaminergic polymorphic ventricular tachycardia

Disease OMIM#

604772

Key considerations

The first line pharmacological regimen is non-selective beta-blockers, without sympathomimetic activity, flecainide is considered the first-choice addition, when the effect of beta-blockers is not complete. In patients who are refractory to pharmacologic treatment, left cardiac sympathetic denervation (LCSD) can be performed. Finally, in patients who are refractory to maximal pharmacologic treatment and LCSD (or LCSD is not available) an implanted cardioverter defibrillator (ICD) is indicated.

Gene

SCN5A

Gene OMIM#

600163

Disease

Long QT syndrome type 3

Disease OMIM#

603830

Key considerations

The treatment of choice for Long QT syndrome affected individuals (symptomatic and asymptomatic) is drug therapy with beta-adrenergic blocking agents. Individuals for whom beta blockers are unsuccessful or contraindicated may be treated by a surgical procedure with left cardiac sympathetic denervation. For affected individuals who have been resuscitated from cardiac arrest (whether on or off beta blockers), treatment with an implantable automatic cardioverter-defibrillator (ICD) is considered.

Gene

SCN5A

Gene OMIM#

600163

Disease

Brugada syndrome

Disease OMIM#

601144

Key considerations

The following can be recommended. Lifestyle changes: avoidance of drugs that may induce ST-segment elevation, avoidance of excessive alcohol intake and large meals, prompt treatment of any fever with antipyretic drugs. Implantation of implantable cardioverter defibrillator (ICD) in patients who are survivors of a cardiac arrest or have documented spontaneous sustained ventricular tachycardia (VT) is recommended. Quinidine or isoproterenol are recommended to treat electrical storms (recurrent episodes of ventricular arrhythmias) and for those individuals who qualify for an ICD but present a contraindication or refuse it. Consideration for catheter ablation is recommended in patients with a history of electrical storms or repeated appropriate ICD shocks. Special recommendations for the athletes are given by American Heart Association and the American College of Cardiology.

Gene

SCN5A

Gene OMIM#

600163

Disease

Dilated cardiomyopathy

Disease OMIM#

601154

Key considerations

Affected individuals should be screened for structural and functional (e.g., arrythmia) heart abnormalities. Treatment of dilated cardiomyopathy may include a) drugs (e.g., angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers), implantable devices (e.g., biventricular pacemaker, implantable cardioverter-defibrillators)

Gene

SDHAF2

Gene OMIM#

613019

Disease

Hereditary paraganglioma-pheochromocytoma syndrome

Disease OMIM#

601650

Key considerations

Blood and urine analysis to detecting elevated levels of catecholamines or its metabolites should be performed. A specialized test, the clonidine suppression test, may be performed to rule out other causes of elevated catecholamines. Imaging techniques such as computed tomography (CT scan) and magnetic resonance imaging (MRI) are often performed to determine the specific location and size of a pheochromocytoma. Surgery is the main form of treatment for pheochromocytoma.

Gene

SDHB

Gene OMIM#

185470

Disease

Hereditary paraganglioma-pheochromocytoma syndrome

Disease OMIM#

115310, 171300

Key considerations

Blood and urine analysis to detecting elevated levels of catecholamines or its metabolites should be performed. A specialized test, the clonidine suppression test, may be performed to rule out other causes of elevated catecholamines. Imaging techniques such as computed tomography (CT scan) and magnetic resonance imaging (MRI) are often performed to determine the specific location and size of a pheochromocytoma. Surgery is the main form of treatment for pheochromocytoma.

Gene

SDHC

Gene OMIM#

602413

Disease

Hereditary paraganglioma-pheochromocytoma syndrome

Disease OMIM#

605373

Key considerations

Blood and urine analysis to detecting elevated levels of catecholamines or its metabolites should be performed. A specialized test, the clonidine suppression test, may be performed to rule out other causes of elevated catecholamines. Imaging techniques such as computed tomography (CT scan) and magnetic resonance imaging (MRI) are often performed to determine the specific location and size of a pheochromocytoma. Surgery is the main form of treatment for pheochromocytoma.

Gene

SDHD

Gene OMIM#

602690

Disease

Hereditary paraganglioma-pheochromocytoma syndrome

Disease OMIM#

168000, 171300

Key considerations

Blood and urine analysis to detecting elevated levels of catecholamines or its metabolites should be performed. A specialized test, the clonidine suppression test, may be performed to rule out other causes of elevated catecholamines. Imaging techniques such as computed tomography (CT scan) and magnetic resonance imaging (MRI) are often performed to determine the specific location and size of a pheochromocytoma. Surgery is the main form of treatment for pheochromocytoma.

Gene

SMAD3

Gene OMIM#

603109

Disease

Loeys-Dietz syndrome

Disease OMIM#

613795

Key considerations

The following treatments are recommended: blood-pressure lowering medications (angiotensin receptor blockers and or beta-blockers); a baseline CTA or MRA of the head, neck, chest, abdomen, and pelvis to detect and monitor aneurysm formation and/or dissections; continued monitoring of the aorta through annual echocardiograms is necessary. Vascular surgery can be a treatment option as a preventative surgery for individuals with a rapidly enlarging aorta or artery.

Gene

SMAD4

Gene OMIM#

600993

Disease

Juvenile polyposis syndrome

Disease OMIM#

174900

Key considerations

Management involves routine colonoscopy. Endoscopic polypectomy is the gold standard for treatment. Due to the risk of cancer and polyposis extension, surgical colectomy (large bowel removal) may be proposed.

Gene

SMAD4

Gene OMIM#

600993

Disease

Hereditary haemorrhagic telangiectasia

Disease OMIM#

175050

Key considerations

The therapeutic treatments for HHT were intended to reduce the symptoms of the disease. However, new drug, bevacizumab (anti-VEGF antibody), has been introduced recently that target VEGF (vascular endothelial growth factor) and the angiogenic pathway.

Gene

STK11

Gene OMIM#

602216

Disease

Peutz-Jeghers syndrome

Disease OMIM#

175200

Key considerations

General cancer screening for anyone with PJS: Upper endoscopy and video capsule endoscopy, beginning at age 8. If polyps are seen, this should be repeated every 2 to 3 years. If no polyps are seen at age 8, these should be repeated by age 18, and then every 2 to 3 years afterwards.

Gene

TGFBR1

Gene OMIM#

190181

Disease

Loeys-Dietz syndrome

Disease OMIM#

609192

Key considerations

The following treatments are recommended: blood-pressure lowering medications (angiotensin receptor blockers and or beta-blockers); a baseline CTA or MRA of the head, neck, chest, abdomen, and pelvis to detect and monitor aneurysm formation and/or dissections; continued monitoring of the aorta through annual echocardiograms is necessary. Vascular surgery can be a treatment option as a preventative surgery for individuals with a rapidly enlarging aorta or artery.

Gene

TGFBR2

Gene OMIM#

190182

Disease

Loeys-Dietz syndrome

Disease OMIM#

610168

Key considerations

The following treatments are recommended: blood-pressure lowering medications (angiotensin receptor blockers and or beta-blockers); a baseline CTA or MRA of the head, neck, chest, abdomen, and pelvis to detect and monitor aneurysm formation and/or dissections; continued monitoring of the aorta through annual echocardiograms is necessary. Vascular surgery can be a treatment option as a preventative surgery for individuals with a rapidly enlarging aorta or artery.

Gene

TMEM127

Gene OMIM#

613403

Disease

Hereditary paraganglioma-pheochromocytoma syndrome

Disease OMIM#

171300

Key considerations

Blood and urine analysis to detecting elevated levels of catecholamines or its metabolites should be performed. A specialized test, the clonidine suppression test, may be performed to rule out other causes of elevated catecholamines. Imaging techniques such as computed tomography (CT scan) and magnetic resonance imaging (MRI) are often performed to determine the specific location and size of a pheochromocytoma. Surgery is the main form of treatment for pheochromocytoma.

Gene

TMEM43

Gene OMIM#

612048

Disease

Arrhythmogenic right ventricular cardiomyopathy

Disease OMIM#

604400

Key considerations

Primary treatment involves arrhythmic medications and anticoagulants. In patients with persistent symptomatic arrhythmias, ablation of conduction pathways may be attempted. Patients with any high risk of sadden death require insertion of an implantable cardioverter-defibrillator (ICD). Heart failure is treated in the usual way, with diuretics, ACE inhibitors and anticoagulants, in severe cases, cardiac transplantation may be required.

Gene

TNNI3

Gene OMIM#

191044

Disease

Hypertrophic cardiomyopathy

Disease OMIM#

613690

Key considerations

Affected Individuals may be treated with drugs. If drug therapy does not work, a permanent pacemaker or defibrillator may be implanted. Surgery may be a treatment option in case of restricted blood flow.

Gene

TNNT2

Gene OMIM#

191045

Disease

Dilated cardiomyopathy

Disease OMIM#

601494

Key considerations

Affected individuals should be screened for structural and functional (e.g., arrythmia) heart abnormalities. Treatment of dilated cardiomyopathy may include a) drugs (e.g., angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers), implantable devices (e.g., biventricular pacemaker, implantable cardioverter-defibrillators)

Gene

TNNT2

Gene OMIM#

191045

Disease

Hypertrophic cardiomyopathy

Disease OMIM#

115195

Key considerations

Affected Individuals may be treated with drugs. If drug therapy does not work, a permanent pacemaker or defibrillator may be implanted. Surgery may be a treatment option in case of restricted blood flow.

Gene

TP53

Gene OMIM#

191170

Disease

Li-Fraumeni syndrome

Disease OMIM#

151623

Key considerations

Children. Adrenocortical carcinoma: ultrasound of abdomen and pelvis every 3 to 4 months; complete urinalysis every 3 to 4 months: blood tests every 4 months (β-human chorionic gonadotropin, alpha-fetoprotein, 17-OH-progesterone, testosterone, dehydroepiandrosterone sulphate, and androstenedione) Brain tumour: annual brain MRI; soft tissue and bone sarcoma; annual, rapid whole-body MRI. Leukaemia or lymphoma: complete blood count (CBC), erythrocyte sedimentation rate, lactate dehydrogenase every 4 months. Adults. Breast cancer: monthly breast self-examination, starting at age 18; clinical breast examination twice a year, annual breast MRI (mammography) and twice-yearly clinical breast examination, which is an examination by a health professional, beginning at age 20 to 25 (mammograms should not be started younger than age 30)

Gene

TPM1

Gene OMIM#

191010

Disease

Hypertrophic cardiomyopathy

Disease OMIM#

115196

Key considerations

Affected Individuals may be treated with drugs. If drug therapy does not work, a permanent pacemaker or defibrillator may be implanted. Surgery may be a treatment option in case of restricted blood flow.

Gene

TRDN

Gene OMIM#

603283

Disease

Catecholaminergic polymorphic ventricular tachycardia

Disease OMIM#

615441

Key considerations

The first line pharmacological regimen is non-selective beta-blockers, without sympathomimetic activity, flecainide is considered the first-choice addition, when the effect of beta-blockers is not complete. In patients who are refractory to pharmacologic treatment, left cardiac sympathetic denervation (LCSD) can be performed. Finally, in patients who are refractory to maximal pharmacologic treatment and LCSD (or LCSD is not available) an implanted cardioverter defibrillator (ICD) is indicated.

Gene

TRDN

Gene OMIM#

603283

Disease

Long QT syndrome

Disease OMIM#

n/a

Key considerations

The treatment of choice for Long QT syndrome affected individuals (symptomatic and asymptomatic) is drug therapy with beta-adrenergic blocking agents. Individuals for whom beta blockers are unsuccessful or contraindicated may be treated by a surgical procedure with left cardiac sympathetic denervation. For affected individuals who have been resuscitated from cardiac arrest (whether on or off beta blockers), treatment with an implantable automatic cardioverter-defibrillator (ICD) is considered.

Gene

TSC1

Gene OMIM#

605284

Disease

Tuberous sclerosis complex

Disease OMIM#

191100

Key considerations

Ultrasound of the kidneys every 1 to 3 years. Magnetic resonance imaging (MRI) or computed tomography (CT or CAT) scans of the kidneys, following an ultrasound evaluation.

Gene

TSC2

Gene OMIM#

191092

Disease

Tuberous sclerosis complex

Disease OMIM#

613254

Key considerations

Ultrasound of the kidneys every 1 to 3 years. Magnetic resonance imaging (MRI) or computed tomography (CT or CAT) scans of the kidneys, following an ultrasound evaluation.

Gene

TTN

Gene OMIM#

188840

Disease

Dilated cardiomyopathy (truncating variants only)

Disease OMIM#

604145

Key considerations

Affected individuals should be screened for structural and functional (e.g., arrythmia) heart abnormalities. Treatment of dilated cardiomyopathy may include a) drugs (e.g., angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-blockers), implantable devices (e.g., biventricular pacemaker, implantable cardioverter-defibrillators)

Gene

VHL

Gene OMIM#

608537

Disease

Von Hippel-Lindau syndrome

Disease OMIM#

193300

Key considerations

Affected individuals may develop various malignancies including retinal hemangioblastomas, cerebellar hemangioblastomas, kidney cancer, epididymal cystadenomas, spinal cord hemangioblastomas, endolymphatic sac tumours, brain stem hemangioblastomas, pheochromocytomas/paragangliomas, pancreatic neuroendocrine tumours, broad ligament cystadenomas. Screening for new tumours or active surveillance for known tumours are both very important aspects of care.

Gene

WT1

Gene OMIM#

607102

Disease

WT1-related Wilms tumour

Disease OMIM#

194070

Key considerations

Screening should be carried out by renal ultrasonography every 3–4 months. Surveillance should continue until 5-7 years of age.

Let us take a look at an example! 

Familial hypercholesterolemia is a genetic disorder that affects the metabolism of lipoproteins and is characterized by severely elevated special cholesterol levels (so called low density lipoproteins). In the early stages, this disease will not display any symptoms. However, if left untreated, atherosclerosis may take place manifesting in the future as chest pain, heart attacks, and even sudden death. Disease causing (so called pathogenic) changes of your DNA sequence (variants) in 3 genes lead to this genetic disease. If a person has a pathogenic variant in one of these gene, he/she is diagnosed with this condition. Available treatment options can reduce the cholesterol concentration in the body, i.e., to delay or even stop cholesterol accumulation and thus preventing atherosclerosis. 

Thus, if 

1) you order a product, that does not include the 3 genes whose pathogenic variants cause Familial hypercholesterolemia

but

2) you consent incidental findings to be reported

and

3) at least one pathogenic variant in the 3 gene(s) is detected 

your medical report will include this incidental finding(s) of Familial Hypercholesteremia. Arcensus also offers you a professional genetic counseling. Whenever you want to receive further clarifications or want to speak to one of our genetic experts, please contact us at the email address [email protected]