NEWBORN T-CELL RECOMBINATION EXCISION CIRCLE SCREENING REVEALS NON-ARCHETYPAL DIGEORGE PATIENT

Abstract

Introduction DiGeorge Syndrome (DGS) is a spectrum of disorders with variable manifestations including congenital heart malformations, immunodeficiency, facial dysmorphism, hypocalcemia, and developmental delay, leading to diagnosis at a wide age range.1 Patients without classic cardiac malformations frequently remain undiagnosed longer, diagnosed only after developing recurrent infections, learning difficulties, or mental health problems. 2 Case Description We report a patient with no family history or physical examination findings suggestive of DGS who had a positive newborn screen (T-cell Recombination excision circle [TREC] level below reference range), concerning for severe combined immunodeficiency (SCID). Subsequent evaluation demonstrated T-cell lymphopenia, confirmed by flow cytometry. Genetic testing identified the typical 22q11.2 microdeletion of DGS. Discussion Although DGS has variable expressivity, prior diagnosis has always been reliant on clinically prominent manifestations (such as structural heart anomalies, facial dysmorphism, recurrent infections or developmental problems). This patient had an uncommon path to diagnosing DGS, solely via newborn TREC without any additional physical manifestations or problems. This case demonstrates immunologist to consider DGS in patients without characteristic facial features, cardiac defects, or family history, especially as DGS is common cause of low TRECs. 4 Developmental issues affect most if not all DGS children, including those without the typical physical features.5 A patient without overt physical or commonly checked laboratory findings of DGS would have likely presented much later, thus missing opportunities for early developmental interventions. Early intervention programs achieve their best results when initiated as soon after birth as possible, and early diagnosis of DGS allows for such interventions. DiGeorge Syndrome (DGS) is a spectrum of disorders with variable manifestations including congenital heart malformations, immunodeficiency, facial dysmorphism, hypocalcemia, and developmental delay, leading to diagnosis at a wide age range.1 Patients without classic cardiac malformations frequently remain undiagnosed longer, diagnosed only after developing recurrent infections, learning difficulties, or mental health problems. 2 We report a patient with no family history or physical examination findings suggestive of DGS who had a positive newborn screen (T-cell Recombination excision circle [TREC] level below reference range), concerning for severe combined immunodeficiency (SCID). Subsequent evaluation demonstrated T-cell lymphopenia, confirmed by flow cytometry. Genetic testing identified the typical 22q11.2 microdeletion of DGS. Although DGS has variable expressivity, prior diagnosis has always been reliant on clinically prominent manifestations (such as structural heart anomalies, facial dysmorphism, recurrent infections or developmental problems). This patient had an uncommon path to diagnosing DGS, solely via newborn TREC without any additional physical manifestations or problems. This case demonstrates immunologist to consider DGS in patients without characteristic facial features, cardiac defects, or family history, especially as DGS is common cause of low TRECs. 4 Developmental issues affect most if not all DGS children, including those without the typical physical features.5 A patient without overt physical or commonly checked laboratory findings of DGS would have likely presented much later, thus missing opportunities for early developmental interventions. Early intervention programs achieve their best results when initiated as soon after birth as possible, and early diagnosis of DGS allows for such interventions.