KPTN gene homozygous variant‐related syndrome in the northeast of Brazil: A case report

Abstract

Alteration of the KPTN gene, responsible for the coding of kaptin (a protein involved in actin cytoskeletal dynamics), causes a syndrome characterized by macrocephaly, neurodevelopmental delay and epileptic seizures. We report the first Brazilian case of KPTN gene variation, previously described in nine subjects from four interlinked families from an Amish community in Ohio, two Estonian siblings and a 9‐year‐old boy from Kansas City. We report a case of KPTN‐related syndrome in a 5‐year‐old child which presented macrocephaly, muscular hypotonia, and global development delay. The neurological examination revealed below‐expected performance in coordination and balance tests, dyspraxia, and hand‐mouth synkinesia. Expressive language was characterized by phono‐articulatory imprecision, abundance of phonological processes and morphosyntactic immaturity. Neuropsychological assessment revealed intellectual disability with impairment of verbal and executive functions. Exome sequencing was performed. Analysis revealed a homozygous 2‐nucleotide duplication c.597_598dup p.(Ser200Ilefs*55) in the KPTN gene, which is predicted to lead to a translational frameshift and formation of a premature stop codon. The phenotypic profile is similar to the cases described in the other families. Presence of macrocephaly and delayed development indicate the possibility of KPTN gene variation. Genetic testing should be carried out at an early stage in order to reach a timely diagnosis.

Pathogenic variants in KPTN, a rare cause of macrocephaly and intellectual disability

“…We report two female Spanish siblings, homozygous for a dinucleotide duplication at Chr19:47984018_47984019dup (hg19): NM_007059.3: c.597_598dup p.(Ser200Ilefs*55) in the KPTN gene. The same variant has already been described by Lucena et al (2020) in a Brazilian girl.…”

“…Interestingly, both siblings in the present report showed delayed anterior fontanel closure. The younger sister also showed brain anomalies, as did patient 5 reported by Baple et al (2014) and two additional patients reported by Thiffault et al 2020 (Baple et al, 2014;Pajusalu et al, 2015;Thiffault et al, 2020;Lucena et al, 2020), but no information was provided regarding the age of onset of the metabolic or endocrine problems. Although our patients did not present behavioral, endocrinological or metabolic alterations, or seizures at the time of this study, they are still fairly young and these aspects need to be followed up closely.…”

“…They are the only children of a healthy nonconsanguineous couple with no family history of note. Similarly to the patient described by Lucena et al (2020), the paternal and maternal families come from different parts of Spain and do not share any family names. Both sisters were born at term, following uneventful pregnancies.…”

“…tinct condition characterized by macrocephaly, neurodevelopmental delay, and seizures (Baple et al, 2014). So far, 13 patients from families harboring either homozygous or compound heterozygous pathogenic variants in KPTN have been reported (Baple et al, 2014;Lucena et al, 2020;Pajusalu et al, 2015;Thiffault et al, 2019).…”

“…While the first nine patients described by Baple et al (2014) belonged to four related families from an Anabaptist community of Ohio, there was no evidence of consanguinity in the family history of T A B L E 1 Comparison of clinical manifestations in affected individuals reported to date with pathogenic variants in KPTN gene Baple et al, 2014Pajusalu et al, 2015Thiffault et al, 2020Lucena et al, 2020…”