Premature aging syndrome, Pentinnen type E34.8

Penttinen M. 1997

Penttinen syndrome, a premature aging syndrome (progeria) is caused by a heterozygous mutation in the PDGFRB gene on chromosome 5q32.

Penttinen syndrome is characterized by a prematurely aged appearance with lipoatrophy, skin atrophy, and keloid hypertrophic scars, thin hair, proptosis, underdeveloped cheekbones, and marked acroosteolysis (Johnston et al. 2015).

Penttinen et al. (1997) reported a 10-year-old Finnish boy with prematurely aged appearance, delayed bone maturation and tooth development, marked acroosteolysis with brachydactyly, and striking skin findings, including hard, confluent skin lesions with some clinical and histological similarity to those of juvenile hyaline fibromatosis . He also had hyperopia, sensorineural hearing loss, and elevated levels of TSH. Length growth and intellectual functions were normal.

Zufferey et al (2013) reported two unrelated patients, a 15-year-old girl of North Vietnamese and Chinese descent and a 20-year-old Frenchman, who had Penttinen-type progeroid syndrome. Although they lacked the classic progeroid facial shape, the patients presented a prematurely aged appearance with premaxillary and maxillary retraction, pseudoprognathism, proptosis, and a flat occiput their thumbs and hallucinations were large, broad, and spatulate. Her hair was sparse but without alopecia. The permanent teeth were normal, although the deciduous teeth were still present. They exhibited ocular pterygia, diffuse keloid-like skin lesions, and acroosteolysis. Length growth was increased despite restricted stature due to kyphoscoliosis. Skin retractions and joint contractures developed in adolescence, and the French patient died of restrictive respiratory failure and cachexia at age 20 years.

Johnston et al. (2015) conducted a follow-up of the Finnish boy originally described by Penttinen et al. (1997) and reported on two other similarly affected individuals. The Finnish patient, who was reexamined at age 29, reported multiple fractures, scoliosis requiring surgical treatment, and osteoporosis. His anterior and posterior fontanelles were still open and each measured approximately 5 cm x 3 cm. He had sparse hair, prognathism, closely spaced eyes, a long nose with a convex ridge, an extremely narrow philtrum and palate, partial eruption of four maxillary teeth, and retrognathia. He had severe contractures and shortening of the fingers and toes, with small, broad, and thick toenails. Ophthalmological examination revealed bilateral temporal and nasal corneal edema, occludable angles in the anterior segment of the eye, simple microphthalmos (nanophthalmos) and retinal striations with shallow orbits. The previously observed nodules and scarring lesions had regressed, although he had thin skin with marked venous patterning and hyperkeratotic palms and soles, with significant corneal formation on the soles.

In a boy of Indonesian and Chinese ancestry with penttine-type premature aging syndrome, Johnston et al. (2015) performed exome sequencing and identified heterozygosity for a de novo defective mutation in the PDGFRB gene (V665A; 173410.0006). This gene defect could be detected in all patients known so far.

1. Johnston J et al (2015) A point mutation in PDGFRB causes autosomal-dominant penttinen syndrome. Am J Hum Genet 97: 465-474.
2. Penttinen M et al (1997) New progeroid disorder. Am J Med Genet 69: 182-187.
3. Zufferey F et al (2013) Acro-osteolysis, keloid-like lesions, distinctive facial features, and overgrowth: two newly recognized patients with premature aging syndrome, Penttinen type. Am J Med Genet 161A: 1786-1791.