Inheritance of Febrile Seizures in Sudden Unexplained Death in Toddlers

• Published in: Pediatric neurology Vol. 46; no. 4; pp. 235 - 239
• Main Authors: Holm, Ingrid A., MD, MPH, Poduri, Annapurna, MD, MPH, Crandall, Laura, PT, MA, Haas, Elisabeth, MPH, Grafe, Marjorie R., MD, PhD, Kinney, Hannah C., MD, Krous, Henry F., MD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01-04-2012; Elsevier
• Subjects: Autopsy; Biological and medical sciences; Child; Child, Preschool; Children; Death, Sudden; Female; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Heredity; Hippocampus; Humans; Infant; Male; Medical sciences; Nervous system (semeiology, syndromes); Neurology; Pediatrics; Pedigree; Seizures; Seizures, Febrile - genetics; Seizures, Febrile - pathology; Sleep; Cardiovascular disease; Cardiocirculatory arrest; Nervous system diseases; Neurological disorder; Febrile convulsion; Sudden death
• ISSN: 0887-8994; 1873-5150
• DOI: 10.1016/j.pediatrneurol.2012.02.007

Abstract Sudden unexplained death in toddlers has been associated with febrile seizures, family history of febrile seizures, and hippocampal anomalies. We investigated the mode of inheritance for febrile seizures in these families. A three-generation pedigree was obtained from families enrolled in the San Diego Sudden Unexplained Death in Childhood Research Project, involving toddlers with sudden unexplained death, febrile seizures, and family history of febrile seizures. In our six cases, death was unwitnessed and related to sleep. The interval from last witnessed febrile seizure to death ranged from 3 weeks to 6 months. Hippocampal abnormalities were identified in one of three cases with available autopsy sections. Autosomal dominant inheritance of febrile seizures was observed in three families. A fourth demonstrated autosomal dominant inheritance with incomplete penetrance or variable expressivity. In two families, the maternal and paternal sides manifested febrile seizures. In this series, the major pattern of inheritance in toddlers with sudden unexplained death and febrile seizures was autosomal dominant. Future studies should develop markers (including genetic) to identify which patients with febrile seizures are at risk for sudden unexplained death in childhood, and to provide guidance for families and physicians.