Disease | Gene(s) | Approximate age of onset (years) | Incidence (estimate) | Clinical action (for child or younger adult) | Likely clinical action (for elderly) | Implication for family |
---|---|---|---|---|---|---|
Hereditary breast and ovarian cancer | BRCA1, BRCA2, PALB, ATM | 30–80 | 1:800 | Surgery, chemoprevention, screening | Annual mammography, MRI; possible bilateral salpingooophorectomy or prophylactic mastectomy | Predictive test for first-degree relative (50:50 risk) |
Lynch syndrome—hereditary non-polyposis colorectal cancer | MLH1, MSH2, MSH6, PMS2 | 35 | 1:800 | Primary prevention (Nonsteroidal anti-inflammatory drugs), screening, early colonoscopy | Colonoscopy, gynae surveillance | Predictive test for first-degree relative (50:50 risk) |
Romano-Ward, Long QT syndrome (LQTS) types 1, 2 and 3, Brugada syndrome (cardiac) | KCNQ1, KCNH2, SCN5A | <18 for LQTS; infant to >80 for Brugada | 1:8000 | Antiarrhythmic drugs | Exercise test, flecainide challenge | Predictive test for first-degree relative (50:50 risk) |
Familial hypercholesterolaemia | LDLR, APOB, PCSK9 | Mid-20s to late adulthood | 1:1000 | Diet/lifestyle changes, statins | Statins | Predictive test for first-degree relative (50:50 risk) |
Dilated cardiomyopathy | TPM1, MYL3, ACTC1, PRKAG2, GLA, MYL2, LMNA | Highly variable | 1:2500 | Pharmacological, surgical, pacemakers, implantable defibrillators | Echocardiogram | Predictive test for first-degree relative (50:50 risk) |
Marfan syndrome, Loeys-Dietz syndrome, familial thoracic aortic Aneurysms and Dissections | FBN1, TGFBR1, TGFBR2, SMAD3, ACTA2, MYLK, MYH11 | Highly variable | 1:10 000 | Surgery, chemoprevention, screening | Echocardiogram | Predictive test for first-degree relative (50:50 risk) |
retinoblastoma | RB1 | <5 | 1:30 000 | Ophthalmology, paediatric oncology, pathology and radiation oncology | Minimal––possibly eye exam | Predictive test for first-degree relative (50:50 risk) |
Hypertrophic cardiomyopathy | MYBPC3, MYH7, TNNT2, TNNI3 | Adolescence to 70+ | <1:50 000 | Pharmacological, surgical, pacemakers, implantable defibrillators | Echocardiogram | Predictive test for first-degree relative (50:50 risk) |
Li-Fraumeni syndrome (heritable cancer) | TP53 (and CHEK2) | Children and young adults, before 45 | <1:50 000 | Standard cancer treatment, avoiding radiation therapy | Avoid irradiation, surveillance | Predictive test for first-degree relative (50:50 risk) |
Peutz-Jeghers syndrome (polyps) | STK11 | Young adulthood | <1:50 000 | Endoscopic surveillance with polypectomy, family testing | Endoscopy surveillance | Predictive test for first-degree relative (50:50 risk) |
Familial adenomatous polyposis of the colon (APC, Gardner syndrome) | APC (and MUTYH) | 20 | <1:100 000 | Colectomy | Colonoscopy | Predictive test for first-degree relative (50:50 risk) |
Tuberous sclerosis complex (TSC) | TSC1, TSC2 | Childhood–30 | 1:100 000 | Mechanistic target of rapamycin (mTOR) inhibitors, neurosurgery, antiepileptic drugs | Renal scans | Predictive test for first-degree relative (50:50 risk) |
Neurofibromatosis type 2 | NF2 | 18–24 | 1:100 000 | Surgical, MRI screens | MRI | Predictive test for first-degree relative (50:50 risk) |
Catecholaminergic polymorphic ventricular tachycardia | RYR2 (and CALM1) | 7–12; rare cases >30 | 1:100 000 | Antiarrhythmic medication | Echocardiogram | Predictive test for first-degree relative (50:50 risk) |
Arrythmogenic right ventricular dysplasia/cardiomyopathy | PKP2, DSP, DSC2, TMEM43, DSG2 | 32–40 | 1:100 000 | Antiarrhythmic medication, implantable cardioverter-defibrillators | Echocardiogram, MRI | Predictive test for first-degree relative (50:50 risk) |
Malignant hyperthermia susceptibility | RYR1, CACNA1S | Only after anaesthetic | 1:100 000 | Ventilation, dantrolene, cooling | Anaesthetic advice | Predictive test for first-degree relative (50:50 risk) |
Von Hippel Lindau syndrome | VHL | Young adulthood | 1 in 36 000; high penetrance; so estimate <1:100 000 | Screening | Surveillance evidence based- renal scans, plasma metanephrine | Predictive test for first-degree relative (50:50 risk) |
Multiple endocrine neoplasia type 1 (MEN1) | MEN1 | 20–25 | <1:300 000 | Parathyroidectomy, biochemical screening | Surveillance | Predictive test for first-degree relative (50:50 risk) |
Hereditary paraganglioma- pheochromocytoma syndrome | SDHD, SDHAF2, SDHC, SDHB | 30 | <1:300 000 | Early surveillance, followed by pharmacological adrenergic receptor blockade and surgery | Surveillance | Predictive test for first-degree relative (50:50 risk) |
Multiple endocrine neoplasia type 2: | RET | 50–70 | <1:350 000 | Parathyroidectomy, biochemical screening | Surgery––thyroidectomy | Predictive test for first-degree relative (50:50 risk); surgery––thyroidectomy in childhood—consider grandchildren |
Familial medullary thyroid cancer | RET (and NTRK1) | 0–70 | <1:350 000 | Parathyroidectomy, biochemical screening | Surgery––thyroidectomy | Predictive test for first-degree relative (50:50 risk); surgery––thyroidectomy in childhood—consider grandchildren |
PTEN hamartoma tumour syndrome | PTEN | 20–30 | <1:400 000 | Screening | Imaging | Predictive test for first-degree relative (50:50 risk) |
Ehlers-Danlos syndrome––vascular type | COL3A1 | 30–40 | 1:500 000 | Medical, surgical management of pain | Clinical assessment | Predictive test for first-degree relative (50:50 risk) |
ACMG, American College of Medical Genetics.