A rare homozygous PPP1R15B variant in a child with diabetes, microcephaly, and growth failure.

Diabetes mellitus can occur in patients who present with neurodevelopmental and systemic abnormalities, potentially indicating underlying syndromic monogenic forms. Autosomal dominant forms of monogenic diabetes are relatively well characterized compared with recessively inherited forms. Here, we present a case of a 17-year-old male patient with postnatal growth failure, microcephaly, motor and intellectual disability, bilateral sensorineural hearing loss, and insulin-dependent diabetes diagnosed at the age of 9 years, in whom a new homozygous variant in the PPP1R15B gene was identified. This gene plays a regulatory role in the cellular response to endoplasmic reticulum (ER) stress. Variants in PPP1R15B can lead to prolonged ER stress, cellular dysfunction, and apoptosis, particularly in pancreatic β cells. To date, only three families with PPP1R15B variants have been reported. Our patient showed unique clinical features, including postnatal growth retardation and early-onset diabetes. This case highlights the importance of investigating monogenic causes in patients with syndromic diabetes and contributes to our understanding of the pathogenic role of ER stress-related mechanisms in such presentations.