Cardiogene: an innovative multidisciplinary consultation for genetic arrhythmias

Introduction: Over the past decade clinically relevant progress has been made regarding the genetic origin of sudden cardiac death due to arrhythmic syndromes such as congenital long QT syndrome (LQTS), Brugada syndrome (BrS), catecholinergic polymorphic ventricular tachycardia (CPVT) and short QT (SQTS). An increased number of patients are diagnosed and their offspring sent for screening. In order to optimize care of these families we have set up a multidisciplinary consultation, "Cardiogene", consisting of a pediatric and an adult cardiologist and a clinical geneticist. All families are seen at a common consult in order to take the family history, genetic background and to explain the disease to patients and their families. Appropriate cardiac investigations and genetic testing are then performed and the families seen again in a multidisciplinary fashion for the results. We have reviewed all our cases over the past 5 years. Methods: retrospective review of all cases seen at Cardiogene Clinic for suspicion of arrhythmic syndromes since 2007. Results: 23 families were seen at the Cardiogene Clinic with a total of 41 children. The suspected arrhythmic syndrome was LQTS in 14 families (26 children), BrS in 7 families (14 children), SQTS in1 family (2 children) and CPVT in 1 family (3 children). Of the 41 children 17 were genetically positive for an arrhythmic syndrome: 14 were for LQTS, 3 for BrS. 24 children were genetically negative however 4 of those were phenotypically positive: 2 LQTS, 1 BrS and 1 CPVT. In 3 families the diagnosis was initially made in a child and then found in the parent. In 2 families the diagnosis was made after a sudden death of one of their children, 1 LQTS (3 week old child), 1 BrS (20 year old). Discussion: Genetic testing is an essential part of diagnosis and permits an improved targeting of patients needing follow-up and treatment. In our series, a mutation has been found in most families with LQTS. In all other genetic arrhythmias, the yield of genetic testing is less but nevertheless helpful for medical care of these pts. Conclusion: A multidisciplinary approach to genetic arrhythmias permits a better and more efficient screening and therapy in affected families. It helps families to better understand their disease and improves follow-up in the affected individuals.

Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism-pathogenesis, diagnosis and treatment.

Congenital hypogonadotropic hypogonadism (CHH) is a rare disorder caused by the deficient production, secretion or action of gonadotropin-releasing hormone (GnRH), which is the master hormone regulating the reproductive axis. CHH is clinically and genetically heterogeneous, with >25 different causal genes identified to date. Clinically, the disorder is characterized by an absence of puberty and infertility. The association of CHH with a defective sense of smell (anosmia or hyposmia), which is found in ∼50% of patients with CHH is termed Kallmann syndrome and results from incomplete embryonic migration of GnRH-synthesizing neurons. CHH can be challenging to diagnose, particularly when attempting to differentiate it from constitutional delay of puberty. A timely diagnosis and treatment to induce puberty can be beneficial for sexual, bone and metabolic health, and might help minimize some of the psychological effects of CHH. In most cases, fertility can be induced using specialized treatment regimens and several predictors of outcome have been identified. Patients typically require lifelong treatment, yet ∼10-20% of patients exhibit a spontaneous recovery of reproductive function. This Consensus Statement summarizes approaches for the diagnosis and treatment of CHH and discusses important unanswered questions in the field.