PPP1R12A Mutation Presenting With Congenital Jejunal Atresia and Short Stature: A Pediatric Endocrinology Case Report

Area of Science:

• Genetics and Molecular Biology
• Pediatric Endocrinology
• Developmental Biology

Background:

• PPP1R12A gene mutations are associated with urogenital and brain malformation syndrome (UBMS).
• Short stature in children warrants thorough genetic and endocrine evaluation.
• Congenital jejunal atresia can present with complex medical histories.

Purpose of the Study:

• To report a novel case expanding the phenotypic spectrum of PPP1R12A mutations.
• To highlight isolated growth hormone deficiency and jejunal atresia in a patient with a PPP1R12A variant.
• To emphasize the importance of multidisciplinary care and early endocrine referral in pediatric short stature.

Main Methods:

• Whole-exome trio sequencing was performed for genetic analysis.
• Comprehensive endocrine evaluation was conducted, including assessment for growth hormone deficiency.
• Clinical data including medical history, surgical interventions, and developmental milestones were reviewed.

Main Results:

• A de novo heterozygous likely pathogenic mutation in the PPP1R12A gene (c.38A>G, p.(Gln13Arg)) was identified.
• The patient presented with isolated growth hormone deficiency, ectopic posterior pituitary gland, interrupted pituitary stalk, and congenital jejunal atresia.
• Notably absent were genitourinary anomalies and neurodevelopmental deficits, broadening the known phenotype.

Conclusions:

• This case demonstrates that PPP1R12A mutations can cause isolated growth hormone deficiency and jejunal atresia without typical UBMS features.
• Early endocrine assessment is crucial for children with PPP1R12A variants presenting with short stature.
• Multidisciplinary management is essential for optimizing outcomes in patients with complex genetic conditions.