Marfanoid phenotype with intellectual disability associated with NKAP mutation: a case report.

backgroundHackman-Di Donato syndrome (Online Mendelian Inheritance in Man no. 301,039), caused by mutations of the NKAP gene, located in Xq24, is a rare genetic disorder characterized by a Marfanoid phenotype, intellectual disability, and abnormalities of the musculoskeletal system. This condition has only been described in ten patients and two fetuses, who were identified owing to severe heart defects. All previously reported patients had mutations located in exons 8 and 9 of NKAP. CASE PRESENTATION: The proband, a 12-year-old Slavic male individual, presented with a Marfanoid habitus, tall stature, dolichostenomelia, scoliosis of the lumbar spine, moderate pectoral deformity, plano-valgus position of the feet, joint hypermobility, habitual dislocation of the right shoulder joint, arachnodactyly of the hands and feet, elongated face, muscle hypotonia, absence epilepsy, and borderline intelligence. Whole-genome sequencing revealed a missense variant NM_024528.4 chrX:119936358-T > G ENST00000371410.5:c.612A > C ENST00000371410.5 (ENSP00000360464.3):p.Arg204Ser in exon 4 of NKAP, classified as a variant of unknown significance. On the basis of clinical and genomic data, the child was diagnosed with X-linked syndromic intellectual developmental disorder, Hackman-Di Donato type. The pathogenicity of the nucleotide variant of exon 4 of NKAP requires further analysis.

conclusionThe observed case may indicate greater genetic heterogeneity of Hackman-Di Donato syndrome, linking it to mutations not only in exons 8 and 9 but also in other exons of NKAP, though more data on the variant effect, as well as the significance of exon 4 of NKAP functioning is needed. Additionally, the case illustrates the need to test male patients with a Marfanoid phenotype and intellectual disability for mutations in NKAP.