Infantile progeria E34.8

Autosomal recessive (?) inherited or spontaneous mutations of the Hutchinson-Gilford progeria syndrome gene (HGPS gene; gene locus: 1q21.2) and a GGC to GGT mutation in codon 608 of the lamin A gene (LMNA gene; gene locus: 1q21.2) with consecutive disruption of lamin A. This lamin A mutant, also called progerin, leads to a disruption of the normal organization of the nuclear membrane and to genomic instability (Kwak D et al. 2025).

The clinical picture can be summarized purely descriptively under the term "senile dwarfism". Patients appear normal at birth, but they grow 7 times faster than usual.

Failure to thrive is common in the first year of life. In the 1st year of life, symptoms of senility become apparent very quickly.

Integument: parchment-like atrophic skin with translucent veins. Sparse, early graying and falling out scalp hair, underdevelopment of eyelashes and eyebrows. Nail dystrophies.

Extracutaneous manifestations: birth weight usually around 2500 g. Short stature from the 1st year of life. Delayed closure of fontanelles. Teething anomalies. Flexion contractures of large joints and finger joints. Osteolysis of terminal phalanges. Osteoporosis with spontaneous fractures, double-sided coxa valga, deforming arthritis. Atrophy of the subcutaneous fat and muscles; protruding abdomen. Final length barely over 115 cm, final weight barely over 15 kg. Lack of or incomplete sexual maturation. High, squeaky voice. Hypogenitalism. High degree of senility with premature arteriosclerosis, apoplectic insults, coronary insufficiency.

Death mostly before the age of 20 due to consequences of arteriosclerosis (cerebral insults, myocardial infarction)

1. Cao H et al. (2003) LMNA is mutated in Hutchinson-Gilford progeria (MIM 176670) but not in Wiedemann-Rautenstrauch progeroid syndrome (MIM 264090). J Hum Genet 48: 271-274
2. Chigira S et al. (2003) Increased expression of the huntingtin interacting protein-1 gene in cells from hutchinson Gilford syndrome (progeria) patients and aged donors. J Gerontol A Biol Sci Med Sci 58: B873-878
3. DeBusk F (1972) The Hutchinson-Gilford syndrome. J Pediatr 80: 697-742
4. Delgado Luengo W et al. (2002) Del(1)(q23) in a patient with Hutchinson-Gilford progeria. Am J Med Genet 113: 298-301
5. Eriksson M et al. (2003) Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423: 293-298
6. Gilford H (1897) On a condition of mixed premature and immature development. Med Chir Transact (London) 80: 17-45
7. Gilford H (1904) Progeria: a form of senilism. Practitioner (London) 73: 188-217
8. Gilford H (1904) Ateleiosis and progeria: continuous youth and premature old age. BMJ 2: 914-918
9. Gilkes JJH et al (1974) The premature ageing syndromes. Br J Dermatol. 91: 243-262
10. Hutchinson J (1886) Congenital absence of hair and mammary glands with atrophic condition of the skin and its appendages in a boy. Trans Med Chir Soc (Edinburgh) 69: 473-477
11. Hutchinson J (1886) A case of congenital absence of hair with atrophic condition of the skin and its appendages.Lancet 1: 923
12. Kwak D et al. (2025) Sclerotic skin in Hutchinson-Gilford progeria syndrome: Reversible senescent phenotype. J Dtsch Dermatol Ges 23:878-880.
13. Wollina U et al (1992) Hutchinson-Gilford syndrome. Dermatologist 43: 453-457