A 2-month-old boy presented with clusters of clonic seizures affecting his left upper and lower extremities. Good seizure control was obtained using carbamazepine. From around the age of 4 months, the patient exhibited episodes of unprovoked and inappropriate laughter without any apparent triggers. Each episode lasted approximately 2 to 3 minutes and occurred several times a day ([Video 1]). He exhibited developmental delay; neither responsive laughter was observed nor was head control achieved by 9 months of age. Trio-based exome sequencing revealed a recurrent heterozygous de novo variant in RHOBTB2 (c.1448G > A, p(Arg483His)), which is known to cause developmental epileptic encephalopathy in early infancy.[1]

Pathological laughter is classically exemplified by gelastic seizures in patients with hypothalamic hamartomas. In genetic disorders, inappropriate and/or paroxysmal laughter is known as a behavioral feature of Angelman syndrome,[2] Pitt–Hopkins syndrome,[3] and Mowat–Wilson syndrome.[4] Patients with RHOBTB2 variants can manifest a happy demeanor and paroxysmal laughter as a behavioral feature.[1] RHOBTB2-related neurodevelopmental disorder should be added to the list of differential diagnoses for abnormal and excessive laughter.

Received: 25 September 2025

Accepted: 11 November 2025

Article published online:
19 January 2026

© 2026. Thieme. All rights reserved.

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany