A 15-month-old boy is brought to the emergency department by ambulance after an episode of "jerking movements" at home. The patient was sitting in the living room with his toys when he suddenly developed uncontrollable rhythmic jerking of his extremities that lasted approximately 2 minutes. His eyes deviated leftward, and he was nonresponsive during this event. The patient did not hit his head before or after the incident. He creeps but has not begun crawling or pulling to stand. The patient says "mama" but speaks no other words. Growth parameters are at the 50th percentile for age and sex. His vital signs are within normal limits. Physical examination shows hypopigmented lesions on the patient's back. Cardiopulmonary examination is unremarkable. Genetic testing in the patient shows a mutation in the tuberous sclerosis complex 1 (TSC1) gene. Which of the following comorbidities is the predominant cause of death in patients with tuberous sclerosis?

Question

A 15-month-old boy is brought to the emergency department by ambulance after an episode of "jerking movements" at home.  The patient was sitting in the living room with his toys when he suddenly developed uncontrollable rhythmic jerking of his extremities that lasted approximately 2 minutes.  His eyes deviated leftward, and he was nonresponsive during this event.  The patient did not hit his head before or after the incident.  He creeps but has not begun crawling or pulling to stand.  The patient says "mama" but speaks no other words.  Growth parameters are at the 50th percentile for age and sex.  His vital signs are within normal limits.  Physical examination shows hypopigmented lesions on the patient's back.  Cardiopulmonary examination is unremarkable. Genetic testing in the patient shows a mutation in the tuberous sclerosis complex 1 (TSC1) gene.  Which of the following comorbidities is the predominant cause of death in patients with tuberous sclerosis?

Quizplus · Accepted Answer

Explanation: The natural history of tuberous sclerosis complex (TSC) is progressive, and neurologic impairment is the leading cause of death in patients with TSC. Patients usually have significant developmental delays and uncontrollable seizures. Death may be due directly to tumors (mass effect from subependymal tumors) or from impairment caused by tumors (eg, status epilepticus, aspiration pneumonia). Optimal seizure control is strongly associated with prolonged life span. For these reasons, a brain MRI and electroencephalogram should be obtained when TSC is initially diagnosed. (Choice A) Cardiac rhabdomyomas can cause impaired ventricular filling, outflow tract obstruction, or dysrhythmia (eg, atrial flutter). Most cardiac rhabdomyomas are asymptomatic and regress spontaneously during infancy; therefore, they are not a common cause of death in TSC. (Choice C) Although tumors in TSC may cause significant morbidity and mortality due to mass effect on surrounding structures, they are benign. Malignant transformation is a rare occurrence in TSC. (Choice D) At baseline, patients with TSC are at no higher risk for meningitis than is the general population. Mass effect from central nervous system tumors may lead to hydrocephalus requiring shunt placement, which would increase the risk for hardware-associated meningitis. This outcome remains a rare cause of death in patients with TSC. (Choice E) Renal involvement (obstructive renal angiomyolipoma, renal failure) is the second most common cause of death after neurologic involvement. For this reason, abdominal imaging is part of the initial evaluation for suspected TSC. Educational objective: Neurologic impairment is the leading cause of death in patients with tuberous sclerosis complex. Uncontrollable seizures, aspiration pneumonia, and obstructive hydrocephalus can result from progressive central nervous system involvement. References: Cortical tubers, cognition, and epilepsy in tuberous sclerosis. (http://www.ncbi.nlm.nih.gov/pubmed/21481739) Long-term neurological outcome in children with early-onset epilepsy associated with tuberous sclerosis. (http://www.ncbi.nlm.nih.gov/pubmed/22142783) The Tuberous Sclerosis 2000 Study: presentation, initial assessments and implications for diagnosis and management. (http://www.ncbi.nlm.nih.gov/pubmed/21813552)

A 15-Month-Old Boy Is Brought to the Emergency Department by Ambulance