The diagnosis HGPS is mostly made on the basis of outward appearance: children with Progeria look strongly alike. There is a distinction between classic and non-classic forms of Progeria.
Classic and Non-classic Progeria
HGPS can often be diagnosed with certainty at an older age due to the similarity of the symptoms of children with classic Progeria. There is, however, also a group of patients with Progeria that show symptoms of mandibulo-acral dysplasia (MAD) beside the symptoms of Progeria.
The explanation for this is that MAD is, just as Progeria, caused by badly functioning lamin A. This is explained in further detail in Cause.
Because they do show premature ageing, and eventually show all the symptoms of Progeria but in a different tempo, these children are said to have Progeria. It is called non-classic Progeria. The differences with classic Progeria are:
- The lag in growth is less severe: children with non-classic Progeria grow 1.30 m to 1.45 m, while Progeria patients hardly grow taller than 1.15 m.
- The hair on the head is kept longer and does not disappear completely when they are older.
- Subcutaneous fat is not lost as quickly, and the cheeks and the skin under the chin retain their subcutaneous fat longer. This only disappears at an adult age.
- Bone loss is more visible than it is with Progeria, and occurs in many bones such as in the crown of the skull, jaw, collarbone, finger segments, and ribs. It also occurs in the facial bones (viscerocranium), but only later, at mature age. With much bone loss there is an elevated risk of bone fractures. These children tend to have many fractures as a result, often from the age of 3 or 4 years.
- A certain level of blood relation in the marriage of the parents appears to be more frequent (in the study by Dr. Hennekam, 4 of the 13 families).
- Chance of reaching adult age is higher than for Progeria.
The symptoms of classic Progeria are therefore also present in non-classic Progeria, but the symptoms vary in severity and duration. As a result, the diagnosis Progeria is also justified for the group with non-classic Progeria. Differences in descriptions are important, however, for the prospects of the patients concerned.
The nature and the severity of the symptoms vary. At young age a tight skin may give the child much discomfort.
Congenital (inherited) Progeria
There is a small number of children that show symptoms of Progeria already at birth.
The most important symptoms: low birth weight, absence of subcutaneous fat, very little hair, bone loss in toe- and finger segments, non-closure of the cranial sutures (visible as wide sutures and enlarged fontanelles), a narrow face with slightly bulging eyes and small chin, bone loss at the extremities of the collarbones. Less conspicuous features are: small nipples, absence of earlobes, small, wide nails, prominent joints, noticeably large veins on the head and a hardened, thin skin (scleroderma). All these features can be visible at birth with congenital Progeria. It is probable that there is a special cause for the malfunctioning lamin A in these children, but to date, that has not been studied.
