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.