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DOI: 10.1055/a-2780-2402
Excessive Laughter in RHOBTB2-Related Neurodevelopmental Disorder
Authors
Funding Information This research was supported by the Japan Agency for Medical Research and Development under grant number JP25gn0110083.
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]
Video 1 The patient exhibited excessive laughter at 6 months of age.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.
Publication History
Received: 25 September 2025
Accepted: 11 November 2025
Article published online:
19 January 2026
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References
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- 2 Angelman H. ‘Puppet’ children: a report on three cases. Dev Med Child Neurol 1965; 7 (06) 681-688
- 3 Giurgea I, Missirian C, Cacciagli P. et al. TCF4 deletions in Pitt-Hopkins syndrome. Hum Mutat 2008; 29 (11) E242-E251
- 4 Mowat DR, Croaker GD, Cass DT. et al. Hirschsprung disease, microcephaly, mental retardation, and characteristic facial features: delineation of a new syndrome and identification of a locus at chromosome 2q22-q23. J Med Genet 1998; 35 (08) 617-623