Clinical challenges of an Xp21 contiguous gene deletion syndrome in a newborn and 15 months of follow-up - case report

Abstract

Xp21 contiguous gene deletion syndrome is a rare X-linked disorder caused by interstitial deletions involving neighboring genes such as NR0B1, GK, DMD, and IL1RAPL1, and is clinically associated with primary adrenal insufficiency, glycerol kinase deficiency, Duchenne muscular dystrophy, and neurodevelopmental delay. The phenotype depends on deletion size and gene content. We report a male child with a 4.5 Mb hemizygous deletion at Xp21.3-p21.2 encompassing IL1RAPL1, NR0B1, GK, and exons 61 to 79 of DMD, confirmed by exome sequencing and shown to be maternally inherited. The presented patient was admitted at 8^th day of life due to concerns for primary muscular or metabolic disease. During the second week of life, the patient developed salt-wasting primary adrenal insufficiency with hyponatremia and hyperkalemia. Persistently elevated creatine kinase exceeding 3000 U/L and markedly elevated cardiac biomarkers were observed in the absence of structural and functional cardiac abnormalities. Urinary organic acid analysis demonstrated significant glyceroluria, and severe serum hypertriglyceridemia was attributed to pseudo-hypertriglyceridemia consistent with glycerol kinase deficiency. Early visual impairment with nystagmus and pale optic discs were noted, and by 15 months the child exhibited global developmental delay, most pronounced in gross motor and language domains. This case illustrates the diagnostic challenges and clinical complexity of Xp21 contiguous gene deletion syndromes. In patients with Xp21 deletion syndrome, early molecular diagnosis enables timely hormone replacement, metabolic surveillance, cardiologic follow-up, and structured neurodevelopmental care.

Keywords: Duchenne muscular dystrophy; Xp21 deletion syndrome; case report; contiguous gene deletion syndrome; glycerol kinase deficiency; neurodevelopmental delay; primary adrenal insufficiency.