Hutchinson-Gilford progeria syndrome (HGPS) is a rare but well known entity 
characterized by extreme short stature, low body weight, early loss of hair, 
lipodystrophy, scleroderma, decreased joint mobility, osteolysis, and facial 
features that resemble aged persons. Cardiovascular compromise leads to early 
demise. Cognitive development is normal. Data on 10 of our own cases and 132 
cases from literature are presented. The incidence in the last century in the 
Netherlands was 1:4,000,000. Sex ratio was 1.2:1. Main first symptoms were 
failure to thrive (55%), hair loss (40%), skin problems (28%), and lipodystrophy 
(20%). Mean age at diagnosis was 2.9 years. Growth in weight was more disturbed 
than growth in height, and growth delay started already prenatally. Mean height 
> 13 years was 109.0 cm, mean weight was 14.5 kg. Osteolysis was wide-spread but 
not expressed, except in the viscerocranium, and remained limited to membranous 
formed bone. Lipodystrophy is generalized, only intra-abdominal fat depositions 
remain present. Cardiovascular problems are extremely variable, both in age of 
onset and nature. Stroke and coronary dysfunctioning are most frequent. 
Pathologic findings in coronaries and aorta resemble sometimes the findings in 
elderly persons, but can also be much more limited. Loss of smooth muscle cells 
seems the most important finding. Mean age of demise was 12.6 years. Patients 
can be subdivided in patients with classical HGPS, which follows an autosomal 
dominant pattern of inheritance, (almost) all cases representing spontaneous 
mutations, and in non-classical progeria, in whom growth can be less retarded, 
scalp hair remains present for a longer time, lipodystrophy is more slowly 
progressive, osteolysis is more expressed except in the face, and survival well 
into adulthood is not uncommon. Pattern of inheritance of non-classical progeria 
is most probably autosomal recessive. The cause of HGPS is an abnormally formed 
Lamin A, either directly by a mutated LMNA gene, or through abnormal 
posttranslational processing (ZMPSTE24 gene mutations). Of 34 LMNA mutations 
found in progeria patients, there were 26 classical p.G608G mutations (76%). 
Pathogenesis is most likely to follow several different pathways. Potential 
therapeutic strategies are developed along these lines and include RNA 
interference techniques and inhibition of the dominant-negative influence of 
abnormally formed Lamin A on polymerization with normally formed Lamin A.