Expanding the Phenotype of TLK2-Related Neurodevelopmental Disorder: Longitudinal Presentation in Two Young Adult Females.
Alina Ivaniuk, Eva Kahn, Brendan Lanpher et al.
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Case in brief
Two unrelated young adult females with truncating heterozygous TLK2 variants had developmental delay, neurobehavioral abnormalities, and constipation beginning in infancy. One, aged 26, had autism and developed persistent threatening auditory hallucinations at 24; video-EEG showed no correlate, and the hallucinations were refractory to medical and electroconvulsive therapy. Trio whole-genome sequencing identified a de novo pathogenic variant. The other, aged 19, had developmental delay and intellectual disability, with obesity, metrorrhagia, and hypersomnia suggesting hypothalamic involvement. Sequencing identified a likely pathogenic variant inherited from an asymptomatic mosaic father.
What made this case unusual
The adult presentations included persistent, treatment-refractory auditory hallucinations in one patient and possible hypothalamic features in the other. The authors note that these findings may be independent of TLK2-related neurodevelopmental disorder; their relationship to the disorder remains uncertain.
Diagnostic / clinical pearl
In patients with developmental delay, behavioral abnormalities, and longstanding constipation, TLK2-related neurodevelopmental disorder may be relevant; adult-onset psychosis or possible hypothalamic features may also warrant consideration, although their association is uncertain.
Why it matters
Longitudinal follow-up is needed to clarify whether these adult features belong to the TLK2-related phenotype and to inform understanding of prognosis and management.