84 Progeria
Progeria 835
Hutchinson-Gilford progeria syndrome, HGPS
Premature senility of striking degree, short stature, peculiar facies
Frequency: 1 in 4–8 million live births (approxi- mately 80 cases recorded); 2:1 male/female ratio.
Genetics
Autosomal dominant (OMIM 176670), caused by mutation in the LMNA gene at 1q21.2; paternal age effect; rare familial cases probably due to germinal mosaicism.
Clinical Features
• Low birth weight, growth failure from 1st year onward
• Short stature, absence of sexual maturation
• Atrophy of subcutaneous tissue
• Alopecia, loss of body hair (during 2nd year of life)
• Frontal and parietal bossing, prominent scalp veins
• Small face, thin, beaked nose, micrognathia
• Delayed dentition, crowded teeth
• Absent/hypoplastic earlobes
• Flexion of knees
• Prominent joints
• Short, dystrophic nails
• Premature aging, premature arteriosclerosis, coronary artery disease (death in 2nd decade or earlier)
• High, squeaky voice
• Thin, atrophic, pigmented skin
• Normal intelligence Differential Diagnosis
• Hallermann-Streiff syndrome
• Acrogeria
• Werner syndrome
• Mandibuloacral dysplasia
• Cockayne syndrome
• Wiedemann-Rautenstrauch syndrome
Radiographic Features Skull
• Hypoplastic facial bones, absence of frontal sinus- es, hypoplasia of mastoids
• Bitemporal bossing
• Thin cranial vault, delay in closure of cranial sutures and fontanels, wormian bones
• Micrognathia
• Delayed eruption of teeth Limbs
• Slender long bones Pelvis
• Coxa valga
• Acetabular degeneration
• Progressive hip dislocation Hands and Feet
• Pointed distal phalanges
• Acro-osteolysis of the distal phalanges
• Thickened small joints (periarticular fibrosis) Chest
• Short and thin clavicles
• Progressive thinning and resorption of distal por- tions of clavicles and ribs
• Narrow thorax with thin ribs Generalized Bone Defects
• Fractures (mainly of humerus)
• Osteoporosis
Bibliography
Brown WT. Human mutations affecting aging – a review. Mech Aging Dev 1979; 9: 325–36
DeBusk FL. The Hutchinson-Gilford progeria syndrome.
Report of 4 cases and review of the literature. J Pediatr 1972; 80: 697–724
Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, Durkin S, Csoka AB, Boehnke M, Glover TW, Collins FS. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 2003; 423:
293–8
Gabr M, Hashem N, Hashem M, Fahmi A, Safouh M. Progeria, a pathologic study. J Pediatr 1960; 57: 70–7
Hogan PA, Krafchik BR. Hutchinson-Gilford syndrome.
Pediatr Dermatol 1990; 7: 317–9
Maciel AT. Evidence for autosomal recessive inheritance of progeria (Hutchinson Gilford). Am J Med Genet 1988; 31:
483–7
Mastroiacovo P, Dallapiccola B,Andria G, Camera G, Lungarot- ti MS. Difetti congeniti e sindromi malformative. McGraw- Hill, Milan, 1990
Rodriguez JI, Perez-Alonso P, Funes R, Perez-Rodriguez J.
Lethal neonatal Hutchinson-Gilford progeria syndrome.
Am J Med Genet 1999; 82: 242–8
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Progeria 836
Fig. 84.1.
aPatient 1, age 17 months.
bPatient 1, age 5 years. Short stature, reduced subcuta- neous fat, sparse hair, small face with prominent subcuta- neous veins, thin nose, micrognathia, premature aging.
(Reprinted, with permission, from Mastroiacovo et al. 1990)
a
b
Progeria 837
P P
Fig. 84.2. Patient 1, age 17 months.
Note osteolysis of the lateral ends of the clavicles. (Reprinted, with permission, from Mastroiacovo et al. 1990)
Fig. 84.3. Patient 1, age 17 months.
Note pointed distal phalanges, with terminal acro-osteolysis, and brachymesophalangy of the 5th finger. (Reprinted, with permis- sion, from Mastroiacovo et al.
1990)
