Ring Chromosome 4

We describe the cytogenomic and clinical characteristics of 47 individuals of ring chromosome 4 (RC4) published in the literature. In nine cases, mosaicism for a normal cell line was observed, but no other forms of constitutional mosaicism involving different stable anomalies of chromosome 4 were reported. All published RC4 were large with distal breakpoints most often in p15-p16 and q34-q35. Given the variability of genomic imbalance related to the different sizes of RC4, there is clinical variability. Individuals with a near complete RC4 often present with normal neurodevelopment, but demonstrate poor growth likely related to the “ring syndrome”. Patients with larger deletions that encompass the 4p Wolf–Hirschhorn critical region present with features of this syndrome. Those with a larger 4q deletion present with variable anomalies. Of note, none of these cases have the characteristic features of the 4q deletion syndrome since the majority had breakpoints that were distal to the typical 4q31-q35 region. Based on this review, it is recommended to obtain imaging for heart and renal anomalies, as well as assessment of vision, hearing, and neurodevelopment. Genetic counseling for the possibility of gonadal mosaicism is also recommended as recurrence in a family has been reported.