Recent studies have further expanded the diagnostic potential of genomic testing in neurodevelopmental disorders. When CMA is combined with trio-based exome sequencing, diagnostic yield can be improved by identifying both copy-number and sequence variants within a single analytical workflow [4]. In addition, advances in CMA interpretation underscore the challenges of classifying rare or novel copy-number variants, emphasizing the need for updated guidelines and standardized reanalysis strategies [5]. Unbalanced chromosomal translocations are a rare cause of developmental delay and congenital anomalies and often result from a clinically silent balanced translocation in a parent [6,7]. We present the case of a Korean infant with an unbalanced rearrangement inherited from her father’s balanced translocation, t(2;20)(p24;p13), resulting in a duplication of 2p25.3–p24.2 and a deletion of 20p13.

This case was reviewed and approved by the Institutional Review Board (IRB) of Keimyung University Dongsan Hospital (IRB No. 2025-10-026), which waived the requirement for informed consent.

A term female infant was referred for genetic evaluation at 1 month of age. The perinatal history was unremarkable. Physical examination revealed a large anterior fontanelle and a sacral dimple. Newborn hearing screening using automated auditory brainstem response (AABR) indicated a ‘refer’ result in the left ear, with no other distinct dysmorphic features identified.

Conventional karyotyping revealed 46,XX,add(20)(p13) (Fig. 1A). CMA identified arr[GRCh37] 2p25.3p24.2(12,770,188–18,905,174)x3 and 20p13(61,568–1,700,861)x1, corresponding to an approximately 6 Mb gain on distal 2p and a 1.6 Mb loss on 20p (Fig. 1D). Parental chromosomal testing was subsequently performed after the proband’s CMA results were obtained, at approximately 2 months of age. Parental studies revealed a normal maternal karyotype and a paternal balanced translocation, 46,XY,t(2;20)(p24;p13), confirming paternally derived unbalanced segregation (Fig. 1B and C). The family was counseled that carriers of balanced translocations face an increased risk of having offspring with unbalanced chromosomal complements, and reproductive options—including prenatal diagnosis and preimplantation genetic testing for structural rearrangements—were discussed.

Although the proband’s initial findings were subtle, the coexistence of a large anterior fontanelle, an abnormal AABR result, and a sacral dimple raised concern for an underlying syndromic process. In neonates, even mild multisystem abnormalities can serve as early indicators of clinically significant genomic rearrangements, supporting the need for timely molecular testing. Interstitial duplication of distal 2p, particularly in the 2p25.3–p24.2 region, has been associated with variable degrees of neurodevelopmental impairment and behavioral problems, largely attributed to dosage effects of the myelin transcription factor 1-like (MYT1L) gene [8]. Distal 2p duplications are generally linked to developmental delays, intellectual disabilities, and craniofacial anomalies, while deletions at 20p13 have been associated with developmental delays, hearing impairments, and neurological disorders [9]. The duplicated 2p25.3–p24.2 interval contains several genes; however, current evidence suggests that MYT1L is the most dosage-sensitive gene in this region. Other genes within the interval, such as syntrophin gamma 2 (SNTG2), acid phosphatase 1 (ACP1), and transmembrane protein 18 (TMEM18), have been described, although their dosage pathogenicity is less well established. Balanced reciprocal translocations in a parent may result in unbalanced chromosomal complements in offspring through abnormal meiotic segregation. In this case, the paternal t(2;20)(p24;p13) most likely underwent adjacent-1 segregation, leading to the transmission of a derivative chromosome containing both the 2p25.3–p24.2 duplication and the 20p13 deletion.

Co-occurrence of these two chromosomal abnormalities is exceedingly rare. A Korean infant with a similar 2p24.2–p25.3 duplication and 20p13 deletion was previously reported by Lee and Shin [5]. However, parental chromosomal studies were not performed in that case; therefore, the underlying mechanism remained unclear. Compared with this previously reported infant, who exhibited facial dysmorphism and postaxial polydactyly and whose chromosomal mechanism could not be determined due to the absence of parental testing, our proband exhibited only subtle neonatal findings and represents the first confirmed case in Korea caused by a paternal balanced translocation t(2;20). Additionally, another Korean family with an unbalanced translocation between chromosomes 2 and 20 at q21 and p13 has been documented [10]. To our knowledge, the present report represents the first Korean case in which the underlying mechanism has been confirmed as the paternal balanced translocation t(2;20)(p24;p13). The clinical findings of this case, compared with previously reported cases of distal 2p duplication and 20p13 deletion, are summarized in Table 1.

The clinical significance of detecting such genomic rearrangements extends beyond diagnosis. CMA can precisely delineate breakpoints and provide genomic resolution that traditional cytogenetic methods cannot achieve [1,2]. Even in seemingly balanced translocations, CMA and sequencing-based breakpoint mapping often reveal cryptic deletions or duplications [6,7]. Thus, combining parental cytogenetic testing with molecular techniques is crucial for elucidating the underlying mechanisms and for accurate recurrence-risk counseling, including prenatal or preimplantation genetic testing.

Population-based studies indicate that CMA increases diagnostic yield by up to 15% in cohorts with developmental delay, supporting its routine implementation in Korean tertiary hospitals [3]. This experience highlights the role of CMA as a standard evaluation tool and underscores the importance of sharing rare structural variants to strengthen genotype–phenotype correlations.

Moreover, even subtle neonatal signs—such as an unusually large anterior fontanelle, abnormal hearing screens, or cutaneous stigmata like a sacral dimple—should prompt thorough neurologic follow-up when pathogenic copy-number changes are identified. Early integration of CMA testing in infants with mild but concerning findings may enable timely diagnosis and earlier developmental intervention.

In summary, CMA identified the proband’s pathogenic copy-number changes; however, parental cytogenetic testing was necessary to define the mechanism and inheritance, enabling accurate recurrence-risk counseling and establishing the first Korean case of a paternally derived unbalanced translocation involving partial trisomy 2p25.3–p24.2 and monosomy 20p13.