Neuropediatrics
DOI: 10.1055/a-2780-2402

Videos and Images in Neuropediatrics

Authors Author Affiliations

Toru Nagata 

1   Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

Toshiki Takenouchi

1   Department of Pediatric Neurology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan

Funding Information This research was supported by the Japan Agency for Medical Research and Development under grant number JP25gn0110083.   Buy Article(opens in new window) Permissions and Reprints(opens in new window)

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]

Download VideoVideo 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 1 Straub J, Konrad EDH, Grüner J. et al; Deciphering Developmental Disorders Study. Missense variants in RHOBTB2 cause a developmental and epileptic encephalopathy in humans, and altered levels cause neurological defects in Drosophila. Am J Hum Genet 2018; 102 (01) 44-57 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