ESPE Abstracts

Background: 1q21.1 microdeletion syndrome is a genetic disorder characterized by a spectrum of complex clinical manifestations, including neurodevelopmental abnormalities, short stature, and cardiac anomalies. However, the phenotypic heterogeneity of this condition poses a diagnostic challenge. We report a unique case of a patient who presented solely with short stature, which was later determined not to be caused by a 1q21.1 microdeletion after comprehensive evaluation.

Case Report: This report describes an 8-year and 11-month-old male patient who presented with "short stature," with a height 2.38 standard deviations (SD) below the mean for his age. No other typical clinical symptoms were observed. Comprehensive genetic evaluations, including high-resolution chromosomal microarray analysis and gene sequencing, revealed a pathogenic heterozygous deletion of approximately 1.89 Mb at the chr1:146026972-147913923 locus. Direct relatives (father, uncle, and grandfather) also carried the same 1q21.1 microdeletion and exhibited short stature with height SDs of -2.66, -2.87, and -3.20, respectively. Growth hormone stimulation test indicated a GH peak value of 0.04 μg/L, with no other significant abnormalities noted. The diagnosis of 1q21.1 microdeletion syndrome-related short stature was made, and treatment with recombinant human growth hormone (rhGH) was initiated. After one year of treatment, the patient's height increased to -1.59 SD. However, follow-up revealed that the grandfather’s sister and brother also exhibited similar short stature, but genetic testing did not indicate a similar deletion. Further family history studies suggested that despite the presence of the 1q21.1 microdeletion in the family and the patient, other factors might be the actual cause of the short stature in this family.

Conclusion: This case underscores the importance of thorough clinical and genetic evaluations for accurate diagnosis of hereditary rare diseases. Even with a family history suggesting a particular genetic disorder, individual patients may have different genetic backgrounds affecting disease manifestation and diagnosis. This case highlights that in families with complex genetic backgrounds, similar phenotypes may have entirely different genetic causes. Therefore, each patient should undergo individualized evaluation and management to ensure accurate diagnosis and appropriate treatment.