Congenital hyperinsulinemic hypoglycaemia in an infant with 9p deletion syndrome

To the editor, Constitutional monosomy of part of the short arm of chromosome 9 (chromosome 9p deletion syndrome, OMIM #158170) results in a rare, complex syndromic condition characterized by developmental delay, craniofacial dysmorphism, and multiple congenital anomalies [1][2][3].Variability in clinical features may be due to differences in the extent of deletion and haploinsufficiency of specific genes.The genotype-phenotype correlation is unclear due to frequent additional chromosomal rearrangements and inconsistent molecular characterization.Gene disruption within the affected region may reveal recessive traits, contributing to the complex presentation [2].Congenital hyperinsulinism (CHI) occurs in less than 10% of patients with chromosome 9p deletion syndrome.Its course can be variable, it may require several years of treatment, and the genetic mechanism underlying dysregulated insulin secretion remains unidentified [4][5][6].Distal duplication of 14q is rare and is characterized by variable clinical features, including developmental delay, growth retardation, low birth weight, hypotonia, short stature, microcephaly, facial dysmorphism, spasticity, and hyperreflexia; brain, cardiac, digital, and skeletal abnormalities are also likely [7][8][9].We present a rare case of CHI in an infant with a karyotype of 46,XX,der(9)t(9p;14q) (p23;q32.2).An 8-month-old female patient was referred to our department for hypoglycemia evaluation.She was the first child born to a 40-year-old mother via cesarean section at 41 weeks of gestation.Her mother had no history of gestational diabetes or other medical conditions, nor did she take any medications during pregnancy.There was no history of diabetes in her father or in three generations of her family.The patient's birth weight, length, and head circumference were 2,990 g (10th-25th percentile), 48 cm (10th-25th percentile), and 35 cm (25th percentile), respectively.After birth, she was admitted to the neonatal intensive care unit because of respiratory failure, hypotonia, cleft palate, and dysmorphic features.Intermittent nasal positive-pressure ventilation was administered immediately after admission because of tachypnea and mild chest retraction.On the first day of life (DOL 1), initial blood glucose level was less than 20 mg/dL.She developed pneumomediastinum with persistent pulmonary hypertension (PPHN).Continuous glucose infusion (glucose infusion rate [GIR], 11 mg/kg/min) dopamine, dobutamine, milrinone, inhaled prostacyclin for PPHN, and intravenous hydrocortisone (5 mg/kg/day) were administered due to PPHN and the possibility of relative adrenal insufficiency.On DOL 2, glucose level reached 29 mg/dL, and a detectable serum insulin level of 93.6 U/mL, undetectable ketone bodies (0.3 mmol/L), and a normal ammonia level of 51 mol/L were observed.Echocardiography revealed a mild atrial septum defect, nearly closing the patent ductus arteriosus, and mild septal hypertrophy.Brain magnetic resonance imaging showed a thinning of the corpus callosum, and small T1 hyperintensity in the left frontal deep white matter, suggesting a small hemorrhagic lesion.Karyotyping revealed 46,XX,add(9)(p23).Chromosome microarray analysis (Affymetrix CytoScan 750K Array, Thermo Fisher Scientific, Santa Clara, CA, USA) with human genomic reference sequence GRCh37/hg19 revealed an approximately 10-Mbp deletion at 9p24.3p23, classified as a pathogenic copy number variant (CNV), an 860-kbp duplication at 14q32.2, considered a variant of uncertain significance, and a 9.8-Mbp duplication at 14q32.2q32.33,also classified as a pathogenic CNV (Fig. 1).The patient's karyotype was considered