P2.L222: Diagnosing Failure to Thrive: A Case of 22q11.2 Deletion Syndrome in Identical Twins

Introduction: 22q11.2 deletion syndrome (22q11.2DS) can present with a wide range of clinical manifestations, thereby posing a diagnostic challenge. Especially in cases when cardinal characteristics of the disease are absent, such as conotruncal cardiac anomalies or immunodeficiency, there may be a delay in diagnosis and interventions for timely growth and development. Failure to thrive is a lesser-known manifestation of 22q11.2DS. However, given that nearly 86% of FTT cases are due to inadequate caloric intake from inorganic causes, a genetic cause as the underlying pathology is often not considered unless other atypical manifestations are present.

Case Description: We present a case of dichorionic diamniotic identical twins diagnosed with de novo 22q11.2DS around 3 months of life who lacked major characteristics, such as congenital heart defects or immunodeficiency. Both infants were admitted and discharged multiple times throughout early life for various reasons, although a consistent concern was failure to thrive and aspiration. Twin B was incidentally found to have asymptomatic hypocalcemia, later confirmed to be primary hypoparathyroidism (low PTH) that persisted beyond the neonatal period. Between outpatient visits and hospital admissions, genetic testing was ultimately sent and confirmed the patient had 22q11.2DS. Twin A did not have any symptoms apart from failure to thrive and aspiration; his calcium, phosphorus, and PTH levels were appropriate for age. Genetic testing was sent due to his brother’s results, and he was ultimately confirmed to have the same mutation.

Discussion: As most cases of DiGeorge syndrome—a phenotypic presentation of 22q11.2DS —are de novo mutations, a negative family history should not remove it from consideration in a failure to thrive evaluation. Similarly, the patients had the most common genetic variant for 22q11.2DS yet still had no landmark features. Two of the most well described genes impacted by this deletion are the T-Box 1 Transcription factor (TBX1) and the DiGeorge Critical Region 6 (DGCR6). TBX1 and DGCR6 are involved in the development of the pharyngeal apparatus as well as cardiac progenitor cells which correlates to the classic presentations seen. This case emphasizes not only how complex the ultimate phenotype of 22q11.2DS is but the importance of maintaining a broad differential even when evaluating common problems as they may have an uncommon source.

Conclusion: This case encourages consideration for 22q11.2DS when creating a differential for failure to thrive, even though the classic symptoms may be absent or delayed in presentation. Early recognition allows for early intervention which leads to favorable outcomes in affected individuals. In this specific case of failure to thrive, in the setting of 22q11.2DS, G tube placement was found to be effective in eliminating malnutrition and preventing further delays in growth and development.