Novel PIK3R1 gene mutation associated with SHORT syndrome: a case report of a 15-year-old female.

OBJECTIVES: To present the clinical journey and management of a 15-year-old female with SHORT syndrome, highlighting the diagnostic challenges and the novel genetic mutation identified.

CASE PRESENTATION: A 15-year-old Filipino female was initially seen in a dermatology clinic at 9 years old for axillary skin darkening, indicative of acanthosis nigricans. Early evaluations revealed elevated blood glucose levels, resulting in a pediatric diabetes diagnosis without the usual hyperglycemic symptoms. Her medical history was notable for premature birth, intrauterine growth restriction, a cardiac murmur from patent ductus arteriosus and a bicuspid aortic valve, delayed teething, and distinct dysmorphic features. Genetic testing identified a novel PIK3R1 gene mutation. Treatment with Metformin significantly improved her glycemic control and lipid profiles. The patient also displayed delayed puberty and polycystic ovary syndrome-like symptoms, but growth hormone deficiency was excluded. Endocrine evaluation for her short stature and lipodystrophy confirmed the presence of the PIK3R1 mutation.

CONCLUSIONS: This case highlights the importance of thorough endocrine and genetic evaluations in patients with complex clinical presentations like SHORT syndrome. The identification of a novel PIK3R1 gene mutation expands the understanding of the genetic basis of this syndrome and underscores the need for individualized treatment approaches.