Hutchinson‐Gilford progeria syndrome: oral and craniofacial phenotypes

Abstract

OBJECTIVE-Hutchinson-Gilford progeria syndrome (HGPS) is a rare early-onset accelerated senescence syndrome. In HGPS, a recently identified de novo dominant mutation of the lamin A gene (LMNA) produces abnormal lamin A, resulting in compromised nuclear membrane integrity. Clinical features include sclerotic skin, cardiovascular and bone abnormalities, and marked growth retardation. Craniofacial features include "bird-like" facies, alopecia, craniofacial disproportion and dental crowding. Our prospective study describes dental, oral soft tissue, and craniofacial bone features in HGPS.METHODS-Fifteen patients with confirmed p.G608G LMNA mutation (1-17 years, 7 males, 8 females) received comprehensive oral evaluations. Anomalies of oral soft tissue, gnathic bones and dentition were identified.RESULTS-Radiographic findings included hypodontia (n=7), dysmorphic teeth (n=5), steep mandibular angles (n=11), and thin basal bone (n=11). Soft tissue findings included ogival palatal arch (n=8), median sagittal palatal fissure (n=7), and ankyloglossia (n=7). Calculated dental ages (9months-11y2m) were significantly lower than chronological ages (1y6m-17y8m) (p=0.002). Eleven children manifested a shorter mandibular body, anterior/posterior cranial base and ramus, but a larger gonial angle, compared to age/gender/race norms.CONCLUSION-Novel oral-craniofacial phenotypes and quantification of previously reported features are presented. Our findings expand the HGPS phenotype and provide additional insight into the complex pathogenesis of HGPS.

Craniofacial Abnormalities in Hutchinson-Gilford Progeria Syndrome

“…Mandible, Maxilla, TMJ, Zygomatic Arches, and Parotid Glands Our findings confirm and expand on the factors affecting oral maxillary function. 11,27 We observed temporomandibular abnormalities and thin gracile zygomatic arches, which have not been previously reported. A mixed dentition of the teeth of the mandible and maxilla has been described, giving rise to a "double row" appearance 12 and reflects our common observation of a V-shaped palate and a disorganized dentition.…”

“…Hypoplastic mandibles have been described, more prominently affecting the mandibular rami, steep mandibular angles, aberrantly positioned condylar processes, and loss of basal bone height. 27 We identified short mandibular rami in combination with flattened mandibular condyles, shallow glenoid fossae, and hypoplastic or absent articular eminences. The flattened appearance of the condylar head bears a similarity to the abnormal remodeled metaphyses seen elsewhere in the appendicular skeleton in HGPS.…”

Microstomia: A Rare but Serious Oral Manifestation of Inherited Disorders

“…According to Domingo et al, Progerin accumulation in cells has been associated with instability of the nuclear membrane, progressive nuclear damage, and premature cell death. Polex and Hegele have shown structural nuclear abnormalities in 48% of Hutchinson-Gilford progeria syndrome fibroblast nuclei compared with less than 6% of normal control cells (Domingo et al, 2009). Furthermore, they stated that, HutchinsonGilford progeria syndrome fibroblasts undergo hyperproliferation followed by rapid apoptosis.…”

“…Lamin A contributes to nuclear structural integrity and chromatin regulatory mechanisms (Martin, 2005). Progerin is the mutant form of lamin A and while progerin is expressed at very low levels normally, it is expressed at much greater levels in Hutchinson-Gilford progeria syndrome (Domingo et al, 2009). According to Domingo et al, Progerin accumulation in cells has been associated with instability of the nuclear membrane, progressive nuclear damage, and premature cell death.…”

“…From the Greek geras, meaning _old age,' progeria is a human disease model of accelerated senescence (Domingo et al, 2009). Affected individuals typically appear normal at birth but begin to demonstrate features of accelerated aging within the first year of life.…”