A patient with constitutional ring 1 chromosome characterized by SNP array CGH.

Constitutional ring chromosomes are a rare cytogenetic abnormality found in humans believed to form by deletion and subsequent fusion at the telomeres. In addition to deleted genomic material, the instability of the ring structure itself may contribute to an abnormal phenotype, specifically growth failure 1. It has also been suggested that larger ring structures are more labile and result in more severe growth retardation than smaller rings 2. While ring structures have been reported in various autosomes, only six patients with constitutional ring 1 chromosome have been reported to date 1, 3, 4, 5, 6, 7. The oldest reported individual lived to be at least 12 years of age 3. Consistently overlapping features in ring 1 chromosome include: microcephaly, low birth weight with severe postnatal growth retardation and dwarfism, intellectual disability, and mild dysmorphic features 4. However, the paucity of reported individuals with ring 1 chromosome limits delineation of a distinct syndrome and provides few opportunities to perform additional cytogenetic investigations. The relatively recent advent of array comparative genomic hybridization allows for further characterization of various microdeletion syndromes. Of particular interest to patients with ring chromosome structures are telomeric deletions (1q44 and 1p36 for chromosome 1). Chromosome 1q43q44 deletion syndrome (OMIM 612337) has been reported in over 70 individuals 8 and has a recognizable phenotype, including: “intellectual disability, prenatal growth retardation, severe microcephaly, hypospadias, corpus callosum abnormalities, cardiac anomalies, gastroesophageal reflux, and characteristic facies” 9. The facial features associated with 1q43q44 deletion include: round face, flat nasal bridge, epicanthal folds, hypertelorism, and low‐set ears; however, various other features have also been reported 8, 9, 10. Several candidate genes have been identified by analyzing the smallest regions of overlap in affected individuals. For example, seizures are thought to be associated with deletion of FAM36A, HNRNPU, and C10RF199 genes, agenesis of the corpus callosum due to deletions of ZNF238 and AKT3, and microcephaly due to deletion of AKT3 8, 9, 10. Based on the clinical overlap between patients with 1q43q44 deletion and those with ring 1 chromosome, it seems reasonable to suggest that the deletion of this region during formation of the ring structure is at least partially responsible for the abnormal phenotype. However, the characterization of deleted regions in reported patients with constitutional ring 1 chromosome has been cytogenetically limited to traditional banding techniques. Additionally, the ring structure further complicates interpretation of genotype‐phenotype correlations in these patients, as mitotic instability may contribute to a “ring syndrome” that is not entirely explained by microdeletions alone. Here, we present a 36‐month‐old male with a constitutional ring 1 chromosome. To our knowledge, this is the first patient with a ring 1 chromosome that has been characterized by comparative genomic hybridization. His confirmed 1q43q44 deletion encompasses the FAM36A, HNRNPU, C10RF199, ZNF238, and AKT3 candidate genes, among many others. He displays a number of clinical signs consistent with the previously described phenotypes of ring 1 chromosome and chromosome 1q43q44 deletion syndrome. Our patient also shows novel clinical features, which may represent incidental findings or an expanded clinical phenotype of this chromosomal abnormality. This patient report provides additional data on ring 1 chromosome and potential genotype‐phenotype correlations.