Distal 22q11.2 microdeletion with mild DiGeorge-spectrum features in a preterm infant: A case report
Shadi Sadeghian, Michael Sgro, Karen Carlyle, Carolyn Jarman, Douglas M. CampbellBackground:
In preterm infants, hypotonia and feeding difficulty are common and often attributed to physiologic immaturity. When these findings persist to term-corrected age, or occur alongside even minor congenital anomalies, a genetic etiology should be reconsidered. 22q11.2 deletions at the distal end of the broader DiGeorge/velocardiofacial region can present with an attenuated phenotype and may be missed without genomic testing.
Case:
A female infant at 31 + 5 weeks gestational age was born via cesarean section for fetal bradycardia. Non‑invasive prenatal testing was low risk for chromosomal anomalies, and the obstetric history was relatively unremarkable, aside from a left‑sided multicystic dysplastic kidney. At birth, she was non‑dysmorphic and required brief positive‑pressure ventilation and short‑term nasal respiratory support. Despite comprehensive feeding support, she demonstrated persistent low tone, poor feeding cues, and ineffective suck at term‑corrected age. Physical exam was unremarkable, except for mild generalized hypotonia. Given ongoing oromotor dysfunction with unilateral renal anomaly, a chromosomal microarray was performed. It demonstrated a likely pathogenic 737 kb deletion at 22q11.2, overlapping the distal region of the recurrent 3 Mb DiGeorge/velocardiofacial deletion, not the proximal 1.5 Mb critical region. Postnatal evaluation revealed decreased T‑lymphocyte lines with B‑cell hyperplasia, normal echocardiogram and parathyroid function, and unremarkable brain MRI.
Management and Outcome:
Management included cue‑based oral trials with occupational/feeding therapy, nasogastric nutrition at home, renal prophylaxis with antibiotics, immunology follow‑up, and genetics counselling. The diagnosis clarified the prognosis and structured multidisciplinary surveillance.
Conclusion:
Distal 22q11.2 deletions can present in the newborn period with subtle hypotonia and feeding dysfunction and may lack the classic cardiac or endocrine findings of proximal (classic) DiGeorge/velocardiofacial syndrome. In preterm infants whose feeding and tone do not improve as expected, particularly when minor anomalies are present, early chromosomal microarray should be considered to identify atypical 22q11.2 deletions and guide syndrome-specific care.