Disease progression in Hutchinson-Gilford progeria syndrome: impact on growth and development.
OBJECTIVE
Hutchinson-Gilford progeria syndrome is a rare and uniformly fatal segmental "premature aging" disease that affects a variety of organ systems. We sought to more clearly define the bone and weight abnormalities in patients with progeria as potential outcome parameters for prospective clinical trials.


METHODS
We collected and analyzed longitudinal medical information, both retrospectively and prospectively, from a total of 41 children with Hutchinson-Gilford progeria syndrome spanning 14 countries, from the Progeria Research Foundation Medical and Research Database at the Brown University Center for Gerontology.


RESULTS
In addition to a number of previously well-defined phenotypic findings in children with progeria, this study identified abnormalities in the eruption of secondary incisors lingually and palatally in the mandible and maxilla, respectively. Although bony structures appeared normal in early infancy, clavicular resorption, coxa valga, avascular necrosis of the femoral head, modeling abnormalities of long bones with slender diaphyses, flared metaphyses, and overgrown epiphyses developed. Long bones showed normal cortical thickness centrally and progressive focal demineralization peripherally. The most striking finding identified in the retrospective data set of 35 children was an average weight increase of only 0.44 kg/year, beginning at approximately 24 months of age and persisting through life, with remarkable intrapatient linearity. This rate is >2 SD below normal weight gain for any corresponding age and sharply contrasts with the parabolic growth pattern for normal age- and gender-matched children. This finding was also confirmed prospectively.


CONCLUSIONS
Our analysis shows evidence of a newly identified abnormal growth pattern for children with Hutchinson-Gilford progeria syndrome. The skeletal and dental findings are suggestive of a developmental dysplasia rather than a classical aging process. The presence of decreased and linear weight gain, maintained in all of the patients after the age of 2 years, provides the ideal parameter on which altered disease status can be assessed in clinical trials.
Gordon
Leslie B
LB
Department of Pediatrics, Rhode Island Hospital, Providence, Rhode Island, USA. leslie_gordon@brown.edu
McCarten
Kathleen M
KM
Giobbie-Hurder
Anita
A
Machan
Jason T
JT
Campbell
Susan E
SE
Berns
Scott D
SD
Kieran
Mark W
MW
D000293:Adolescent; D001835:Body Weight; D018488:Bone Demineralization, Pathologic / Q000235:genetics; D001848:Bone Diseases, Developmental / Q000235:genetics*; D001862:Bone Resorption / Q000235:genetics; D001842:Bone and Bones / Q000002:abnormalities; D002648:Child; D002675:Child, Preschool; D003286:Contracture / Q000235:genetics; D002658:Developmental Disabilities / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005271:Femur Head Necrosis / Q000235:genetics; D006801:Humans; D007180:Incisor / Q000002:abnormalities; D007223:Infant; D007231:Infant, Newborn; D007592:Joint Diseases / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D011371:Progeria / Q000235:genetics*; D011446:Prospective Studies; D012189:Retrospective Studies; D014078:Tooth Eruption