Abstract
Background: Ring chromosome 13 is a rare genetic disorder in which the two ends of chromosome 13 are fused together to form a ring shape. Ring formation subsequently leads to gene deletions on both the long and short arms of the chromosome. Observed phenotypes among these patients are variable due to differences in the number of genetic deletions that occur with fusion. Common clinical features seen in ring chromosome 13 include micro- or anencephaly, severe mental retardation (MR), ambiguous genitalia, growth retardation, and facial dysmorphism. To our knowledge, diabetes mellitus (DM) has only been reported in two published case reports of patients with ring chromosome 13. It has been proposed that development of DM in this syndrome may be due to deletion of the IRS2 gene on the long arm of chromosome 13. This hypothesis is based on evidence from knockout mice studies and genetic comparisons of ring chromosome 13 patients with and without DM.
Clinical Case: We present a case of a 23-year-old woman with a known history of mosaic ring chromosome 13 abnormality who was diagnosed with DM at age 21. Diagnosis was made incidentally based on laboratory data obtained at a routine outpatient visit. Hemoglobin A1c at that time was 13.1%. Glutamic acid decarboxylase and insulin antibodies were negative. She has been on a basal-bolus insulin regimen since diagnosis with overall good glycemic control (average hemoglobin A1c 6.5%). She has no known micro- or macrovascular complications of DM. She has no family history of chromosome 13 syndrome or DM. Other notable clinical features associated with her ring chromosome 13 disorder include MR, spastic encephalopathy, delayed puberty (menarche at age 18), scoliosis, facial dysmorphism, and deficiencies in clotting factors 7 and 10.
Conclusion: DM is a common disorder that is typically multifactorial in etiology. In rare cases, DM can be the result of monogenic mutations or deletions. We present a case of a young woman with early-onset antibody-negative DM thought to be related to gene deletions resulting from her underlying ring chromosome 13 abnormality. There is some evidence from prior case reports and rodent studies to suggest that DM in patients with this disorder may be the result of IRS2 deletion from the long arm of chromosome 13. Although DM is a rare complication of ring chromosome 13 disorder, early screening should be considered in these patients to prevent development of downstream complications.
References:
1. Babaya N, Noso S, Hiromine Y, Ito H, Taketomo Y, Yamamoto T, Kawabata Y, Ikegami H. Early-Onset Diabetes Mellitus in a Patient With a Chromosome 13q34qter Microdeletion Including IRS2. J Endocr Soc. 2018 Sep 11;2(10):1207-1213.
2. Lagergren M, Börjeson M, Mitelman F. Prophase analysis of ring chromosome 13--an attempt at phenotype-karyotype correlation. Hereditas. 1980;93(2):231-3.
Ring Chromosome 13 in an Infant Girl
