A Novel Syndrome of Mandibular Hypoplasia, Deafness, and Progeroid Features Associated with Lipodystrophy, Undescended Testes, and Male Hypogonadism

Abstract

Patients with MDP syndrome have a few overlapping but some distinct clinical features as compared with MAD, suggesting that it is a novel syndrome. The molecular basis of MDP syndrome remains to be elucidated.

Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent <i>de novo</i> mutation in the <i>POLD1</i> gene

“…Therefore, the characteristics of our patient support the view that the primary role of sustained hyperinsulinemia may be as a cause of secondary PCOS, acanthosis nigricans, and hirsutism [35,38,39]. In contrast, undescended testes and hypogonadism have been reported in males [14,16,26].…”

“…To date, 21 patients with POLD1-related MDPL syndrome [11][12][13][14][15][16][17]26] have been reported in English publications, most frequently from European countries ( Table 2). The male-to-female ratio is 7:15.…”

“…Recently, Weedon et al [11] described six cases, two of which were previously reported by Shastry et al [26], as a novel syndrome of mandibular hypoplasia, deafness and progeroid features featuring subcutaneous fat loss and severe insulin resistance (MDPL syndrome). They identified an in-frame heterozygous deletion at the polymerase-active site in exon 15 of POLD1, c.1812 1814delCTC (p.Ser605del) as the cause of the MDPL syndrome [11].…”

Lipodystrophies and Dyslipidemias

“…Mutations in PSMB8 have since also been reported in chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE) syndrome [44,45]. Another novel syndrome reported by us is characterized by mandibular hypoplasia, deafness, progeroid features (MDP)-associated lipodystrophy [46]. All males with MDP had undescended testes and hypogonadism.…”

Congenital generalized lipodystrophies—new insights into metabolic dysfunction

“…[12][13][14][15] By contrast, the other types of lipodystrophy-mandibuloacral dysplasia, autoinflammatory lipodystrophy, progeroid syndromes associated lipodystrophy, SHORT syndrome associated lipodystrophy and Keppen-Lubinsky syndrome associ ated lipodystrophy-are extremely rare and in total each subtype has been reported in no more than 30 patients (Box 1). 10,11,[16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] However, FPLD has autosomal dominant inheritance and some patients with subtle loss of fat from the extremities might not receive an accurate diagnosis; therefore, the prevalence of this lipodystrophy might be higher than is reported. CGL has the most extreme pheno type with loss of nearly all the body fat at birth ( Figure 1) and early development of metabolic complications in childhood.…”