Abstract
OBJECTIVES: Tuberous sclerosis complex (TSC) is a neurocutaneous genetic disorder with a high prevalence of epilepsy and neurodevelopmental disorders. TSC can be challenging to diagnose in infants because they often do not show many clinical signs early in life. In this study, we describe the timing and pattern of presenting and diagnostic features in a prospective longitudinal study of infants with TSC. METHODS: Two multicenter, prospective studies enrolled 130 infants with definite TSC by clinical or genetic criteria and followed them longitudinally up to 36 months of age. Periodic study visits included medical and seizure histories, physical and neurologic examinations, and developmental assessments. Ages at which major and minor features of TSC and seizures were first identified were analyzed. RESULTS: The most common initial presenting features of TSC were cardiac rhabdomyomas (59%) and hypomelanotic macules or other skin findings (39%), and 85% of infants presented with either or both. Ultimately, the most prevalent diagnostic TSC features were hypomelanotic macules (94%), tubers or other cortical dysplasias (94%), subependymal nodules (90%), and cardiac rhabdomyomas (82%). Thirty-five percent of infants presented prenatally, 41% presented at birth or within the first month of life, and 74% met criteria for TSC diagnosis at or within 30 days of presentation. Seizure onset occurred before or at initial presentation in only 15% of infants, but 73% developed epilepsy within the first year of life. CONCLUSIONS: Infants with TSC can often be identified early, before the onset of neurologic sequelae, enabling earlier diagnosis, surveillance, and possibly disease-modifying treatment.
| Original language | English (US) |
|---|---|
| Article number | e20164040 |
| Journal | Pediatrics |
| Volume | 140 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 2017 |
Funding
funding from the US Department of Defense and the Congressionally Directed Medical Research Program and the National Institutes of Health (P20NS080199, U01NS082320, R01NS082649, and U01NS092595); Dr Krueger has received research funding from the National Institutes of Health (U01NS082320 and U01NS092595); and Dr Sahin has received research funding from the National Institutes of Health (U01NS082320, U01NS092595, and U54HD090255) and the US Department of Defense (W81XWH-15-1-0189). Other than the items listed under Potential Conflicts of Interest, the other authors have indicated they have no financial relationships relevant to this article to disclose. and Stroke of the National Institutes of Health under award numbers U01NS082320 and P20NS080199, and by the Tuberous Sclerosis Alliance. Dr Davis is supported by the Neurology Resident Research Education Program of the National Institute of Neurological Disorders and Stroke (R25NS070682), the Boston Children’s Hospital Office of Faculty Development, and the Tuberous Sclerosis Alliance. Dr Wu is supported by the University of California, Los Angeles Clinical and Translational Research Center National Institutes of Health grant UL1TR0000124. Drs Au, Bebin, Wu, Krueger, and Sahin are supported by the Developmental Synaptopathies Consortium (U54NS092090), which is a part of the National Center for Advancing Translational Sciences Rare Diseases Clinical Research Network. The Rare Diseases Clinical Research Network is an initiative of the Office of Rare Diseases Research of the National Center for Advancing Translational Sciences and is funded through collaboration between the National Center for Advancing Translational Sciences, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Funded by the National Institutes of Health (NIH).
ASJC Scopus subject areas
- Pediatrics, Perinatology, and Child Health