A de novo 1.62 Mb deletion at 2q34 with nonpenetrant neurodevelopmental phenotype at 12 months.

BACKGROUND: Interstitial deletions at chromosome 2q34 are rare and have been associated with a spectrum of neurodevelopmental disorders including intellectual disability, epilepsy, autism spectrum disorder, and behavioral abnormalities. The minimal critical region and penetrance of these deletions remain poorly defined. We report a de novo 1.62 Mb 2q34 deletion diagnosed prenatally, with a favorable short-term neurodevelopmental outcome, providing a counter example to the established pathogenic view. MATERIALS AND METHODS: A 41-year-old primigravida woman underwent amniocentesis at 19 weeks of gestation. Copy number variation sequencing (CNV-seq) was performed on fetal amniotic fluid and parental peripheral blood samples. Serial prenatal ultrasounds and postnatal follow-up to 12 months of age were conducted. RESULTS: CNV-seq revealed a de novo 1.62 Mb deletion at 2q34, encompassing three protein-coding genes: LANCL1, CPS1, and ERBB4. Parental validation confirmed the deletion as de novo. Prenatal ultrasounds were largely normal except for a mild, transient deceleration of head growth. The patient was delivered at term with no dysmorphic features. At 12 months of age, the infant showed no significant abnormalities in physical growth, motor milestones, or cognitive development. Head circumference had normalized to within the normal range. CONCLUSION: This report describes a de novo 2q34 deletion involving ERBB4, a gene strongly linked to intellectual disability and epilepsy. However, the absence of any neurodevelopmental abnormalities at 12 months suggests that this deletion may exhibit incomplete penetrance and variable expressivity. This case highlights the complexity of genotype-phenotype correlation for ERBB4 haploinsufficiency and underscores the value of long-term follow-up.