Mandibular hypoplasia, Deafness, Progeroid Features Associated Lipodystrophy Syndrome (MDPL)
MDPL is an  autosomal dominant systemic disorder with about 22 patients reported worldwide till 2018. Classical phenotypic features consist of loss of subcutaneous fat, small mandible resulting in lower teeth overcrowding, premature aging, sensorineural hearing loss, prominent eyes, and a beaked nose. Despite having a low BMI, metabolic abnormalities like diabetes mellitus and hypertriglyceridemia are commonly observed. Males display cryptorchidism and hypogonadism, with certain females presenting with menstrual irregularities like amenorrhea and dysmenorrhea.
Mutations in the Polymerase delta gene (POLD 1) gene that performs DNA synthesis in the lagging strand during DNA replication is responsible for MDPL presentation6.Heterozygous de novo mutations in the POLD 1 gene with most cases involving single codon deletion (p.S605del) lead to the decreased catalytic activity of POLD 1 enzyme with a partially altered proofreading activity, making it the deletion hot spot for MDPL. Some cases have been reported to have a missense mutation (p.R507C) replacing arginine with cytosine.