HGPS (Hutchinson-Gilford Progeria syndrome) is a rare, autosomal dominant inherited disease with an estimated incidence of 1:4 million live births. It was first discovered by Jonathan Hutchinson in 1886. In 1904, Hastings Gilford coined the term progeria, derived from the Greek pro=early and geras=old.
Symptoms and Prognosis for People with Hutchinson-Gilford Progeria
In most cases, clinical manifestations are evident after the first year of life, with an average age at diagnosis of 2.9 years. The appearance of infants with Hutchinson-Gilford Progeria at birth is normal. However, a major decrease in growth occurs during the first year. They present craniofacial dysmorphism with prominent eyes, hooked nose, thin lips, abnormal dentition, micrognathia, prominent ears with absence of earlobes, alopecia, prominent cranial veins, loss of subcutaneous fat, joint stiffness, bone changes and skin changes, which are apparent during the second to third year of life. Death usually occurs in adolescence, secondary to cardiovascular complications. In 2003, Ericksson et al identified mutations in the lamina A gene in 20 of 23 patients with HGPS. Sandre-Giovannoli et al identified mutations in the same gene in 2 patients with Hutchinson-Gilford Progeria.
A 2-year old male patient of mixed race and urban origin was sent to pediatric endocrinology because of short stature, alopecia and dry skin.
He is the product of a second pregnancy complicated by threatened abortion in the first trimester and polyhydramnios without fetal morphological alterations in the second trimester. Delivery was by cesarean section at 39 weeks of gestational age. Birth weight and height were 3,400g and 52cm, respectively. The Apgar test score was 7/7 and the physical examination was normal. It was clear at a later date that he had Hutchinson-Gilford Progeria.
A few days after birth, dry, stiff skin with lesions on the trunk and extremities was observed, and from 2 months onwards, growth retardation (weight and height) and mild hypotonia.
In the physical examination at 2 years the following characteristics were observed in the infant later diagnosed with Hutchinson-Gilford Progeria: weight of 8kg (T (p. Gly608Gly) in exon 11 of the LMNA gene.
Here is the phenotype of a toddler with Hutchinson-Gilford Progeria at 2 years of age. A) Low size at 24 months of age. B, C and D) Prominent alopecia and cranial vasculature, absence of ear lobes. E) Sclerotic skin. F) Drummer stick fingers. G) Prominent knees.
Understanding the Progression of Hutchinson-Gilford Progeria
Phenotype at 2 years of age. A) Low size at 24 months of age. B, C and D) Prominent alopecia and cranial vasculature, absence of ear lobes. E) Sclerotic skin. F) Drummer stick fingers. G) Prominent knees.
Phenotype progression. A) 2 months. B) 4 months. C) 9 months. D) 15 months. E) 24 months F) 29 months.
HGPS belongs to a group of disorders associated to mutations in the LMNA gene or “laminopathies”, including Emery-Dreyfuss muscular dystrophy, dilated cardiomyopathy, Charcot-Marie-Tooth disease type 2B, waist muscular dystrophy type 1B and Dunnigan type partial family lipodystrophy.