Refining the clinical phenotype of Okur-Chung neurodevelopmental syndrome

Abstract

We describe an 8-year-old Japanese boy with a de novo recurrent missense mutation in CSNK2A1, c.593A>G, that is causative of Okur-Chung neurodevelopmental syndrome. He exhibited distinctive facial features, severe growth retardation with relative macrocephaly, and friendly, hyperactive behavior. His dysmorphic features might suggest a congenital histone modification defect syndrome, such as Kleefstra, Coffin-Siris, or Rubinstein-Taybi syndromes, which are indicative of functional interactions between the casein kinase II, alpha 1 gene and histone modification factors.

Figure 1

The proband and cranial magnetic resonance imaging (MRI). The patient at 3 years and 7 months (a) and 7 years and 10 months of age (b), revealing synophrys, hypertrichosis, down-slanting palpebral fissures, and a bulbous nose. Axial T2-weighted view (c) and saggital T1-weighted view (d) of cranial MRI revealing a reduced anterior pituitary gland and delayed myelination.

Figure 2

CSNK2A1 mutation. (a) Electropherogram of the patient and his parents. (b) The mutation occurred at an amino acid residue that is evolutionarily conserved in nine different species. The altered nucleotide is highlighted in the gray box. (c) De novo mutation (c.593A>G, p.K198R) identified in the patient. The CSNK2A1 protein contains four domains: the ATP/GTP binding loop, basic cluster, active site, and activation segment.