A newborn is found to have a small ring chromosome 15 detected by standard karyotype. Microarray analysis reveals absence of 15q11-q13 sequences on this ring chromosome. The phenotype most likely to result from this finding is:

• A Ring chromosome 15 syndrome with features unrelated to PWS/AS imprinting
• B Features of Prader-Willi or Angelman syndrome depending on parental origin of ring chromosome ✓
• C Normal phenotype as ring chromosomes are always supernumerary and non-essential
• D Universal phenotype of short stature and microcephaly from telomeric gene loss

Explanation

When a ring chromosome 15 (r15) is formed and lacks 15q11-q13 sequences (confirmed by FISH or microarray showing deletion of this region), the clinical phenotype depends on whether the ring chromosome is of paternal or maternal origin and whether the intact homologous chromosome 15 compensates. If the r15 is paternal and lacks SNRPN/NDN, the remaining maternal chromosome provides only maternal imprinting pattern — resulting in a Prader-Willi syndrome phenotype. Conversely, if the r15 is maternal and lacks UBE3A, Angelman syndrome features result. This situation can also be complicated by uniparental disomy of the intact chromosome 15 if the ring is derived from one parent. Microarray and methylation studies of 15q11-q13 are essential to determine the molecular basis and predict phenotype.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.