Beckwith-Wiedemann syndrome (BWS) is an imprinting disorder characterized by overgrowth, tumor predisposition, and congenital malformations. It is associated with genetic or epigenetic abnormalities in a cluster of imprinted genes found within a genomic region of approximately one megabase on chromosome 11p15. The imprinted region 11p15 is separated into two domains, with each domain regulated by a functionally independent imprinting control regions (ICR). The centromeric ICR2 regulates the expression of CDKN1C, KCNQ1, and further genes. The majority of cases of BWS show hypomethylation in the ICR2 or mutations in the ICR2-regulated CDKN1C gene. In intron 10 of the KCNQ1 locus, the untranslated KCNQ1OT1 RNA is encoded. KCNQ10T1 is expressed by the paternal allele and probably represses realization of the CDKN1C gene. In the telomeric ICR1, hypermethylation of the H19 promoter and loss of imprinting of IGF2 have been reported in a small fraction of patients with BWS. A few BWS cases could be related to NSD1 deletions or mutations.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD2C Overgrowth syndromes
H00713 Beckwith-Wiedemann syndrome
Romano-Ward syndrome Jervell and Lange-Nielsen syndrome (JLNS) [DS:H02091] Timothy syndrome
Description
Long QT syndrome (LQTS) is a cardiovascular disorder resulting from mutations in cardiac ion channels. LQTS is characterized by prolongation of the QT interval in the electrocardiogram (ECG) and a propensity to torsades de pointes ventricular tachycardia frequently leading to syncope, cardiac arrest, or sudden death usually in young otherwise healthy individuals. Anesthesia in a patient with LQTS can trigger malignant arrhythmias and is therefore a high-risk procedure. There are two well-known syndromes with a long QT interval. The Romano-Ward syndrome is characterized by an autosomal-dominant inheritance without familial deafness. The Jervell and Lange-Nielsen syndrome (JLNS) has an autosomal-recessive pattern of inheritance and is associated with deafness.
Category
Cardiovascular disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
11 Diseases of the circulatory system
Cardiac arrhythmia
BC65 Cardiac arrhythmia associated with genetic disorder
H00720 Long QT syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06528 Calcium signaling
H00720 Long QT syndrome
Plaster NM, Tawil R, Tristani-Firouzi M, Canun S, Bendahhou S, Tsunoda A, Donaldson MR, Iannaccone ST, Brunt E, Barohn R, Clark J, Deymeer F, George AL Jr, Fish FA, Hahn A, Nitu A, Ozdemir C, Serdaroglu P, Subramony SH, Wolfe G, Fu YH, Ptacek LJ
Title
Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome.
Boczek NJ, Best JM, Tester DJ, Giudicessi JR, Middha S, Evans JM, Kamp TJ, Ackerman MJ
Title
Exome sequencing and systems biology converge to identify novel mutations in the L-type calcium channel, CACNA1C, linked to autosomal dominant long QT syndrome.
Yang Y, Yang Y, Liang B, Liu J, Li J, Grunnet M, Olesen SP, Rasmussen HB, Ellinor PT, Gao L, Lin X, Li L, Wang L, Xiao J, Liu Y, Liu Y, Zhang S, Liang D, Peng L, Jespersen T, Chen YH
Title
Identification of a Kir3.4 mutation in congenital long QT syndrome.
Crotti L, Johnson CN, Graf E, De Ferrari GM, Cuneo BF, Ovadia M, Papagiannis J, Feldkamp MD, Rathi SG, Kunic JD, Pedrazzini M, Wieland T, Lichtner P, Beckmann BM, Clark T, Shaffer C, Benson DW, Kaab S, Meitinger T, Strom TM, Chazin WJ, Schwartz PJ, George AL Jr
Title
Calmodulin mutations associated with recurrent cardiac arrest in infants.
Short QT syndrome (SQTS) is a cardiovascular disorder resulting from mutations in cardiac ion channels. The mutation of genes (KCNH2, KCNQ1, and KCNJ2) encoding for cardiac potassium channels plays a central role in SQTS. SQTS is characterized by constantly short QT interval associated with atrial fibrillation, syncopal episodes, and sudden cardiac death. The implantable cardioverter defibrillator (ICD) therapy in patients with a short QT syndrome has an increased risk due to possible T wave oversensing.
Category
Cardiovascular disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
11 Diseases of the circulatory system
Cardiac arrhythmia
BC65 Cardiac arrhythmia associated with genetic disorder
H00725 Short QT syndrome
Priori SG, Pandit SV, Rivolta I, Berenfeld O, Ronchetti E, Dhamoon A, Napolitano C, Anumonwo J, di Barletta MR, Gudapakkam S, Bosi G, Stramba-Badiale M, Jalife J
Title
A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene.
Atrial fibrillation (AF, ATFB) is the most common cardiac arrhythmia and is regarded generally as a sporadic, acquired disorder. Nevertheless, recent growing evidence points to an important heritable basis for AF. By linkage analysis, several loci have been mapped for monogenetic AF. Some of these loci encode for subunits of potassium channels.
Category
Cardiovascular disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
11 Diseases of the circulatory system
Cardiac arrhythmia
Supraventricular rhythm disturbance
BC81 Supraventricular tachyarrhythmia
H00731 Atrial fibrillation
Pathway-based classification of diseases [BR:br08402]
Cellular process
nt06539 Cytoskeleton in muscle cells
H00731 Atrial fibrillation
Endocrine system
nt06325 Hormone/cytokine signaling
H00731 Atrial fibrillation
Chen YH, Xu SJ, Bendahhou S, Wang XL, Wang Y, Xu WY, Jin HW, Sun H, Su XY, Zhuang QN, Yang YQ, Li YB, Liu Y, Xu HJ, Li XF, Ma N, Mou CP, Chen Z, Barhanin J, Huang W
Title
KCNQ1 gain-of-function mutation in familial atrial fibrillation.
Yang Y, Xia M, Jin Q, Bendahhou S, Shi J, Chen Y, Liang B, Lin J, Liu Y, Liu B, Zhou Q, Zhang D, Wang R, Ma N, Su X, Niu K, Pei Y, Xu W, Chen Z, Wan H, Cui J, Barhanin J, Chen Y
Title
Identification of a KCNE2 gain-of-function mutation in patients with familial atrial fibrillation.
Xia M, Jin Q, Bendahhou S, He Y, Larroque MM, Chen Y, Zhou Q, Yang Y, Liu Y, Liu B, Zhu Q, Zhou Y, Lin J, Liang B, Li L, Dong X, Pan Z, Wang R, Wan H, Qiu W, Xu W, Eurlings P, Barhanin J, Chen Y
Title
A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation.
Gollob MH, Jones DL, Krahn AD, Danis L, Gong XQ, Shao Q, Liu X, Veinot JP, Tang AS, Stewart AF, Tesson F, Klein GJ, Yee R, Skanes AC, Guiraudon GM, Ebihara L, Bai D
Title
Somatic mutations in the connexin 40 gene (GJA5) in atrial fibrillation.
Orr N, Arnaout R, Gula LJ, Spears DA, Leong-Sit P, Li Q, Tarhuni W, Reischauer S, Chauhan VS, Borkovich M, Uppal S, Adler A, Coughlin SR, Stainier DY, Gollob MH
Title
A mutation in the atrial-specific myosin light chain gene (MYL4) causes familial atrial fibrillation.
Jervell Lange-Nielsen syndrome (JLNS) is a rare autosomal recessive disorder with congenital deafness and long-QT syndrome. Mutations in the potassium-channel gene KVLQT1 have been identified in JLNS. Recently, mutations in KCNE1 also have been found to cause JLNS.
Category
Cardiovascular disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
11 Diseases of the circulatory system
Cardiac arrhythmia
BC65 Cardiac arrhythmia associated with genetic disorder
H02091 Jervell and Lange-Nielsen syndrome
