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Case Reports
. 2023 Jan 10:13:1113811.
doi: 10.3389/fneur.2022.1113811. eCollection 2022.

Case report: KPTN gene-related syndrome associated with a spectrum of neurodevelopmental anomalies including severe epilepsy

Svea Horn  1   2 , Magdalena Danyel  3   4 , Nina Erdmann  1   2 , Felix Boschann  3   4 , Cecilia Gunnarsson  5   6   7 , Saskia Biskup  8 , Jerome Juengling  8 , Cornelia Potratz  1   2 , Christine Prager  1   2 , Angela M Kaindl  1   2   9
Affiliations
Case Reports

Case report: KPTN gene-related syndrome associated with a spectrum of neurodevelopmental anomalies including severe epilepsy

Svea Horn et al. Front Neurol. .

Abstract

Biallelic variants in the kaptin gene KPTN were identified recently in individuals with a novel syndrome referred to as autosomal recessive intellectual developmental disorder 41 (MRT41). MRT41 is characterized by developmental delay, predominantly in language development, behavioral abnormalities, and epilepsy. Only about 15 affected individuals have been described in the literature, all with primary or secondary macrocephaly. Using exome sequencing, we identified three different biallelic variants in KPTN in five affected individuals from three unrelated families. In total, two KPTN variants were already reported as a loss of function variants. A novel splice site variant in KPTN was detected in two unrelated families of this study. The core phenotype with neurodevelopment delay was present in all patients. However, macrocephaly was not present in at least one patient. In total, two patients exhibited developmental and epileptic encephalopathies with generalized tonic-clonic seizures that were drug-resistant in one of them. Thus, we further delineate the KPTN-related syndrome, especially emphasizing the severity of epilepsy phenotypes and difficulties in treatment in patients of our cohort.

Keywords: KPTN gene; epilepsy; macrocephaly; neurodevelopment delay; splice site variant.

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Conflict of interest statement

SB and JJ were employed by Praxis für Humangenetik Tübingen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
(A) Facial aspect of patient 1 at the age of 6 years showing prominent forehead and hypertelorism. (B) Face of patient 2 at the age of 18 months. Prominent forehead, synophris, hypertelorism and mildly downward slanting palpebral fissures.
Figure 2
Figure 2
(A) Routine electrophalography (EEG) reveals focal sharp-waves (left, frontoparietal), rhythmic 6 Hz electrical activity and signs of focal cerebral dsfunction with a frontal theta-waves slow activity in the frontal area. (B) The EEG examination of patient 2. Frontotemporal sharp-wave complexes on the left side and rhythmical 4–5 Hz activity.
Figure 3
Figure 3
Position of KPTN (NM007059.4) variants identified in this study (top), with respect to the affected exon. (Bottom) Reported pathogenic variants according to the literature.
See this image and copyright information in PMC

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References

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Publication types

Grants and funding

MD is a participant in the BIH-Charité Clinician Scientist Program funded by the Charité–Universitätsmedizin Berlin and the Berlin Institute of Health (BIH). FB is a participant in the Clinician Scientist Program (CS4RARE) funded by the Alliance4Rare and associated with the BIH Charité Clinician Scientist Program. Our research work was supported by the grants from the German Research Foundation (DFG) (grant FOR3004), the Helmholtz Association (HIL-A03), and the Einstein Stiftung Fellowship through the Günter Endres Fond.