ClinVar

In a 2-year-old boy (patient 6) with intellectual developmental disorder with language impairment and early-onset dopa-responsive dystonia-parkinsonism (IDLDP; 619911), Singh et al. (2020) identified a de novo heterozygous 1-bp duplication (c.325dupC, NM_006186.3) in exon 3 of the NR4A2 gene, predicted to result in a frameshift and premature termination (Gln109ProfsTer3). The mutation, which was found by exome sequencing, was not present in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed, but it was predicted to lead to nonsense-mediated mRNA decay and a loss of function with haploinsufficiency. The patient had a severe disorder with poor growth, global developmental delay, and abnormal eye movements apparent in early infancy. He developed focal seizures at age 6 months that progressed to infantile spasms and evolved to Lennox-Gastaut syndrome with refractory tonic and myoclonic seizures. Other features included hypotonia, disordered sleep, and feeding difficulties requiring tube feeding. Brain imaging showed pontine hypoplasia, enlarged ventricles, and delayed myelination.