Epilepsy in a cohort of children with Noonan syndrome and related disorders.

Noonan syndrome (NS) and related disorders encompass a phenotypically heterogeneous group of conditions due to mutations in the Ras/Mitogen-activated protein kinase pathway. The main objective of this study was to assess the presence and characteristics of epilepsy in children and adolescents affected by NS and related disorders. The study included all the patients aged 5-21 years who had been diagnosed with NS or of one of three Noonan-like syndromes (i.e., cardio-facio-cutaneous syndrome, Noonan syndrome with multiple lentigines, and Noonan-like syndrome with loose anagen hair) at a university pediatric hospital. Clinical, EEGs, brain MRIs, and genotype data were extracted from the medical records, and follow-up telephone interviews were conducted to obtain updated information about epilepsy and its course. Out of a total of 75 patients (38 [50.7%] males, median age at assessment 12.0 years [q1 9.0-q3 17.0]; 61 [81.3%] with NS; and 14 [18.7%] with a Noonan-like syndrome), 13 (17.3%) had epilepsy, with median age at onset of 4.0 years (q1 2.0-q3 8.0, min 0.1-max 17.0). Epilepsy was more common among Noonan-like patients (50.0%) than in NS (9.8%, p < 0.001), and its presence was associated with neurodevelopmental delay (p < 0.001, OR 14.6 95% CI 3.6-59.4), cognitive impairment (p = 0.002, OR 11.2 95% CI 2.5-51.0), need for educational support (p < 0.001, OR 21.8, 95% CI 2.6-179.1), and lower adaptive functioning (median [q1-q3]: 54.0 [q1 40.0-q3 77.5] vs 97.0 [q1 76.5-q3 107.0] of the non-epileptic subgroup, p = 0.004). In 10 out of 13 cases (76.9%), the epilepsy outcome was good (i.e., seizure-free for more than 12 months with or without anti-seizure medication). CONCLUSION: Epilepsy was more common in NS than reported in the general population, with a significantly higher rate in Noonan-like syndromes. Epilepsy was associated with neurodevelopmental delay, cognitive impairment, and lower adaptive functioning. WHAT IS KNOWN: • Neurological abnormalities have been reported in NS and related disorders. • There is evidence of a phenotype-genotype relationship for neurological abnormalities. WHAT IS NEW: • Epilepsy was found to be more common in NS and related disorders than typically reported in the general population and associated with neurodevelopmental delay, cognitive, and functional impairment. • The Noonan-like phenotype had a higher frequency of epilepsy than typical NS.

Lidocaine treatment in refractory status epilepticus resulting from febrile infection-related epilepsy syndrome: a case report and follow-up.

We report the management of refractory status epilepticus (SE) by using continuous intravenous infusions of lidocaine in a previously healthy 15-year-old girl with a "catastrophic encephalopathy" in whom a diagnosis of febrile infection-related epilepsy syndrome was supposed. One week after a banal pharyngitis and fever, the patient presented confusion and intractable clusters of seizures. Although she underwent multiple examinations investigating all possible etiologies (intracranial infection, autoimmune disease, or toxic and metabolic illness), all results were negative except a feeble positivity to Mycoplasma pneumoniae serum antibodies. SE was initially treated with benzodiazepine followed by administration of barbiturates and subsequent induction of coma because of refractory SE; different antiepileptic drugs (AEDs) were given at different times in a period of 6 weeks but clinical and electroencephalographic improvements were achieved only after continuous infusion of lidocaine. When she recovered from SE, the patient developed severe psychomotor and cognitive impairment associated with cerebral atrophy. Treatment with lidocaine or other alternative drugs in cases of prolonged SE should be taken into account as soon as it becomes clear that the clinical condition is refractory to common AEDs included in available guidelines for SE treatment, to improve the bad outcome of this severe condition, at least limiting the negative effects of prolonged high metabolic demand due to continuous epileptiform activity and/or the possible negative effects of prolonged burst-suppression coma.