Ring Chromosome 17 Syndrome—A Case Report and Discussion of Diagnostic Methods

Ring chromosome 17 and 17p13.3 deletion syndrome are phenotypically heterogeneous diseases with similar clinical features. The ring chromosome 17 phenotypic features range from the Miller–Dieker syndrome characterized by deletion of the PAFAH1B1 gene, lissencephaly, hypotonia, dysphagia, café au lait spots, and severe intellectual disability, to a milder phenotype characterized by microcephaly, seizures, delayed development, minor facial dysmorphic features, clinodactyly, short stature, café au lait spots, retinal flecking, and deletion of the YWHAE and CRK genes. Similarly, the phenotypic features of the 17p13.3 deletion syndrome range from the Miller–Dieker syndrome caused by loss of function of the PAFAH1B1 gene and characterized by lissencephaly, microcephaly, seizures, hypotonia, and severe intellectual disability to a milder phenotype characterized by nonspecific white matter changes, microcephaly, seizures, delayed development, short stature, and deletion of the YWHAE and CRK genes. Café au lait spots and retinal or axillary freckling have been noted in the ring chromosome 17 syndrome but not in 17p13.3 deletion syndrome. We report a 5-year-old girl with a history of intrauterine growth retardation, short stature, intractable epilepsy, expressive language disorder, clinodactyly, multiple café au lait spots, and retinal freckling who was initially diagnosed with 17p13.3 deletion syndrome involving YWHAE and CRK but not PAFAH1B1 on CGH array. However, cytogenetic analysis of G-banded chromosomes revealed mosaic ring chromosome 17. Optical genome mapping simultaneously identified the 17p13.3 deletion and the mosaic ring chromosome 17. This case report highlights the limitations of the arrays and sequencing methods for identifying structural variants, the need to investigate further deletions and duplications identified by arrays, mainly considering atypical phenotypic features, and suggests that OGM could be used as a first-tier test with exome sequencing for the diagnosis of patients with dysmorphic features, intellectual disability, and seizure disorder.