title: Unusual retrospective prenatal findings in a male newborn with Timothy syndrome type 1.
abstract: Timothy syndrome 1 (TS1) is a multisystem disorder characterized by severe QT prolongation and potentially lethal ventricular arrhythmias in the first years of life, plus other cardiac and extracardiac manifestations caused by mutation in the CACNA1C gene, a CaV1.2 L-type calcium channel. Here, we report retrospectively an unusual fetal presentation on a second patient with TS1 with fetal hydrops due to a congenital AV block and its postnatal diagnosis by a marked prolongation of the corrected QTc interval of 570 ms and a missense mutation, p.Gly406Arg, in exon 8A of CACNA1C gene. The observed manifestations in our patient during fetal period indicate a severe form and they were probably exacerbated by the maternal use of amitriptyline during the first 4 months of pregnancy. Unfortunately, he died at 3 months-old due a ventricular tachycardia and fibrillation related to a septic event. Although difficult to diagnose, possibly most fetuses with TS1 have symptoms of long QT syndrome. Despite the fatal outcome for our patient, an early diagnosis of TS may help to prevent life-threatening events or early death in future patients, especially in developing countries where availability of therapies such as cardioverter defibrillator are very limited, or require time for its funding.
authors.affiliation: Service of Pediatric Genetics and Cytogenetic Unit, Center for Registry and Research in Congenital Anomalies (CRIAC), "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Mexico; "Dr. Enrique Corona Rivera" Institute of Human Genetics, Department of Molecular Biology and Genomics, Health Sciences University Centre, University of Guadalajara, Guadalajara, Mexico. Electronic address: rocorona@cucs.udg.mx.
authors.forename: J Román
authors.initials: JR
authors.lastname: Corona-Rivera
authors.affiliation: Maternal-Fetal Medicine Unit, "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Mexico.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Barrios-Prieto
authors.affiliation: Service of Pediatric Cardiology, "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Mexico.
authors.forename: Rafael
authors.initials: R
authors.lastname: Nieto-García
authors.affiliation: Molecular Cardiology Laboratories, IRCCS Fondazione Maugeri, Pavia, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Bloise
authors.affiliation: Molecular Cardiology Laboratories, IRCCS Fondazione Maugeri, Pavia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Priori
authors.affiliation: Molecular Cardiology Laboratories, IRCCS Fondazione Maugeri, Pavia, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Napolitano
authors.affiliation: Service of Pediatric Genetics and Cytogenetic Unit, Center for Registry and Research in Congenital Anomalies (CRIAC), "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Mexico; "Dr. Enrique Corona Rivera" Institute of Human Genetics, Department of Molecular Biology and Genomics, Health Sciences University Centre, University of Guadalajara, Guadalajara, Mexico.
authors.forename: Lucina
authors.initials: L
authors.lastname: Bobadilla-Morales
authors.affiliation: Service of Pediatric Genetics and Cytogenetic Unit, Center for Registry and Research in Congenital Anomalies (CRIAC), "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Mexico; "Dr. Enrique Corona Rivera" Institute of Human Genetics, Department of Molecular Biology and Genomics, Health Sciences University Centre, University of Guadalajara, Guadalajara, Mexico.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Corona-Rivera
authors.affiliation: Service of Pediatric Genetics and Cytogenetic Unit, Center for Registry and Research in Congenital Anomalies (CRIAC), "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Mexico.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Zapata-Aldana
authors.affiliation: Service of Pediatric Genetics and Cytogenetic Unit, Center for Registry and Research in Congenital Anomalies (CRIAC), "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Mexico.
authors.forename: Christian
authors.initials: C
authors.lastname: Peña-Padilla
authors.affiliation: Service of Pediatric Genetics and Cytogenetic Unit, Center for Registry and Research in Congenital Anomalies (CRIAC), "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Mexico.
authors.forename: Jehú
authors.initials: J
authors.lastname: Rivera-Vargas
authors.affiliation: Service of Pediatric Genetics and Cytogenetic Unit, Center for Registry and Research in Congenital Anomalies (CRIAC), "Dr. Juan I. Menchaca" Civil Hospital of Guadalajara, Mexico.
authors.forename: Eva
authors.initials: E
authors.lastname: Chavana-Naranjo
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000009:adverse effects; D000639:Amitriptyline / Q000009:adverse effects; D001321:Autistic Disorder / Q000175:diagnosis* / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000235:genetics*; D005260:Female; D005318:Fetal Heart / Q000000981:diagnostic imaging / Q000187:drug effects; D006801:Humans; D007231:Infant, Newborn; D008133:Long QT Syndrome / Q000175:diagnosis* / Q000235:genetics; D008297:Male; D020125:Mutation, Missense; D011247:Pregnancy; D013576:Syndactyly / Q000175:diagnosis* / Q000235:genetics; D016216:Ultrasonography, Prenatal
chemical_list: D018759:Adrenergic Uptake Inhibitors; C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type; D000639:Amitriptyline
keywords: Amitriptyline; Atrioventricular block; CACNA1C; Fetal bradychardia; Fetal hydrops; Long QT; Syndactyly