symptoms

symptoms and diagnosis 

Children with Progeria go through normal intellectual and emotional development. During their first years of life, however, it becomes increasingly clear that their physical development does not run its normal course. Growth stagnates, the hair starts to fall out, and they lose subcutaneous fat.

Most children with Progeria show no distinctive signs or defects at birth. On average, they have a slightly lighter birth weight. The first symptoms become visible after a few months. The typical features of Progeria become visible later, during the course of the first years. As a result, the diagnoses are often late and sometimes also inaccurate. In a study [1], the average age of 72 children when they were diagnosed was 2.9 years.

Professor Raoul Hennekam conducted a study of the literature on Progeria and included also the data of 132 patients documented in medical literature. Additionally, he monitored eight Progeria patients during the major part of their life, and examined the medical history of another 16 European Progeria children. Many of his research findings can be found here.

In order to diagnose correctly a child that possibly has Progeria, it is important to be able to make a comparison with other Progeria patients of the same age. Progeria children of the same age have a strikingly similar appearance. Many doctors can establish a diagnosis because they recognise the characteristics of the appearance of the child. The importance the diagnosis has for parents can be illustrated by the fact that virtually all of them remember the exact date at which their child was diagnosed.

development and course of Classic Progeria 

The development of Progeria is very similar in all patients. There are no complications during pregnancy or at childbirth: the children are 200 to 300 grams lighter than average, but otherwise appear to develop well in the beginning. A first symptom is a distinctively visible vein across the nose bridge. During the second half of the first year, or during the second year, physical growth starts to fall behind, which is often accompanied by loss of hair and subcutaneous fat.

The first suspicions that the child may have Progeria mostly arise around the time when the child is between two and three years old. At that time slowly but surely the typical facial features of Progeria start to show: the loss of almost all head hair, save some small, fine downy hair; dilated visible veins on the head, seemingly bulging eyes, a narrow nose, thin skin with wrinkles around the mouth, too little room for the teeth, a small chin, and the ears hardly have an earlobe.

Eventually the face and the body change more and more. The chin becomes smaller; the nose changes shape; the facial bones become smaller; the subcutaneous fat in the face disappears.

The body shows more signs of loss of subcutaneous fat and muscle; the joints are more pronounced and shortened muscles or cramps become worse. It becomes difficult for the children to move their joints, especially their ankles, knees, and fingers.

Meanwhile, the children’s psychosocial and intellectual developments proceed normally. Their speaking ability is generally good, but they have a high shrill voice. Their behaviour is also normal for their age. But they hardly grow; especially their weight increase falls behind. They start to look more and more like a small old person.

The most important health problems that follow concern the heart- and blood vessels. Progeria children can suffer a cerebral infarction at the age of 4 to 5 years old, with consequences for their mobility and speaking ability. Fortunately this does not occur very often.

The heart problems are frequent, however, and occur mostly between the 8th and 12th year, and slowly become worse. Sometimes the heart conditions can be acute.

The decreased mobility and the vascular complaints cost the child a lot of energy. Because of this Progeria children can behave as a normal child only short periods of the day: they are quickly tired.

The average life expectancy is 13 years. The cause of death is often failure of the blood vessels, where a heart attack is the most common.

synonyms for Progeria: 
Hutchinson-Gilford Progeria Syndrome
HGPS
Premature Aging Syndrome
Progeria of Childhood
Progeria Infantiles

Reasons that parents seek medical help for their children in the first year of life:
                  Growth problems (55%)
                  Loss of head hair
                  Skin problems (28%) (often the most striking)
                  Loss of subcutaneous fat (20%)
                  Other symptoms such as a narrow face, a small sharp nose, small cheekbones, and nutrition problems.

symptoms

the first year of life
- The average weight at birth of Progeria children is approximately 3 kg., but the child does not gain sufficient weight and grows too slowly.
- onset of hair loss
- A small blue vein is visible on the bridge of the nose, sometimes also on the (fore)head.
-  of the skin on the chest and stomach: a leather-like skin develops, dry and sometimes with a red colour, build up of excessive subcutaneous fat tissue (lipoedema) (scleroderma).
- motor: a reduced mobility.
- the children develop a small face with large, and slightly bulging eyes.

from the second year of life onwards 

length and weight 
In the second year of life they are lively but fragile children that now hardly grow in length. The growth of the child slows down severely. The average length of Progeria patients of 12 years old can vary between 96 cm to 128 cm; they rarely grow taller than 115 cm.
The weight at 12 years of age ranges from 9.3 kg to 20.7 kg.

growth 
Progeria children grow too slowly. Often, the child will not eat well. Both the increase in weight as in length stay behind, but the weight increases the least. The weight curve of the children from two years onwards is practically horizontal. Also, there is no growth spurt during pre-puberty or puberty. Boys usually grow slighter bigger than girls, but there is greater diversity in the growth pattern of boys than in that of girls.

skin and hair 
- very little, thin, and downy head hair 
- thin, tight, and translucent skin. The skin is hardly elastic, and is extra vulnerable as a result 
- clearly visible veins, especially on the head 
- circles under the eyes 
- noticeably short nails and shortened finger segments (acro-osteolysis). This process starts in the 2nd and 5th finger, and slowly spreads. The fourth finger is often least affected. The skin on the finger segments becomes red and swollen, the nails calcify. 

skin
A tight and hard skin (scleroderma) is one of the symptoms of Progeria that is visible first, but in most cases this symptom is of a temporary nature. In some Progeria children scleroderma was observed already at the first day of their life, but with most it is discovered at an age between six months and one-and-a-half years. This can also be later, at two years of age. The skin is thick, lightly swollen and shows a pressure-point oedema (when pressed with a finger, a ‘dent’ remains that disappears slowly). Sometimes the skin is reddish. This phenomenon is seen mainly on the abdomen, above the buttocks, on the hips and genitalia, but can also appear widespread. Sometimes the area where the skin changes from normal to scleroderma affected skin is marked by a darkly-coloured zone. Scleroderma disappears within six to twenty-four months. Then the skin becomes thin, dry, atrophic, less elastic and sometimes flaky. The neck and the upper part of the chest show extra pigmentation: small, light brown spots. Later, these spots will also appear on the head and limbs.

hair 
Save for a few exceptions, Progeria children are born with normal hair and normal hair colour. However, the hair of the children hardly grows, and usually at an age between six months and two years, the hair starts falling out. Between two and three years, the hair will have virtually disappeared. Often a little bit of hair remains that is fine, dry, and downy. Only very rarely will a Progeria child of 12 to 15 years old still have hair. Also the hair of the eyebrows and eyelashes disappears for the most part, except for a few eyelashes on the side. The hair turns light in colour.

loss of subcutaneous fat and clearly visible veins
Loss of subcutaneous fat can begin from the age of six months, but generally becomes visible around the age of three to four years. It is first visible in the limbs, then the chest and skull, and finally the face. Until that time the children often have round, blushing cheeks. On the belly and hips the subcutaneous fat disappears last. The fat in the belly itself does not disappear, however, and Progeria children may therefore often have a swollen belly.

As a result of the loss of subcutaneous fat and the skin becoming thinner, the veins become more visible. A prominently visible vein over the bridge of the nose is often one of the first symptoms of classic Progeria. Later, the veins on the head become more pronounced and finally over the entire body. Because the fat in the face also disappears, the eyes seem round and somewhat bulging. But, when measured, the eyes are found to be of normal size.

skeleton and joints
- An increasing stiffness in the joints (arthritis) that mostly begins in the finger joints and the knees. Also rheumatic complaints can arise. 
- A deviating position of the legs: somewhat stiff with lightly bent knees. On X-rays it can be seen that the position of the upper leg is turned outward (coxa valga). 
- The chin grows smaller during 1-2 years. The child has a relatively small jaw in which the teeth have too little room. 
- The stagnated growth in Progeria patients can in part be determined by X-rays of the collarbones. Already at young age, X-rays show that the collarbones are seriously shortened. The outer part of the collarbone seems to dissolve, as it were. 


dissolution of bone tissue (Osteolysis)
Bone dissolution is caused by the bone partially dissolving. It especially arises in the following bones:

hands and feet
Usually, bone dissolution is first seen in the finger segments, the segments grow thin. Also the toes are usually affected, but this is less visible. The skin over the affected area becomes red and swollen, causing the fingertips not to seem thin, but thickened. The nails have an irregular, rough surface, and are thin, small, and short.

collarbones 
Apart from bone dissolution in the collarbone (that affects mainly the tips and the outsides of the collarbone), in some children the upper ribs are also affected by bone dissolution. Because of the bone that dissolves in the collarbone and ribs, the upper part of the chest slowly becomes smaller and narrower as bone dissolution continues.

lower jaw
At birth, the chin still has normal dimensions and a normal shape, but the chin diminishes in size after one or two years. In appearance, the face of the child seems to have a withdrawn chin. As a result of the jaw becoming smaller, there is too little room for the teeth, and this causes the teeth to grow crooked.

face 
As the children grow older, the facial bones become smaller and thinner. The nose becomes sharp. Sometimes the nasal septum (the bony and cartilaginous partition between the nasal passages) partly overlaps, causing the tip of the nose to become flattened.

skull 
One of the first symptoms of Progeria is late, or absent, closure of the sutures (the ‘seams’) in the skull. This especially concerns the first fontanel, which can remain open until puberty. The crown of the skull is largely dependent on the growth of the brain, and because the brain keeps growing the crown of the skull is normal sized, or large. This, together with the bone dissolution in the facial bones and the small jaw, causes the skull to be relatively large compared to the face.

hip joint
Older patients often experience complaints in the hip joint (dislocation).

mobility 
The movement of the joints is normal at birth. The knees are usually the first joints to experience stiffness, followed by elbows and fingers. This happens around the second or third year. The position of the legs is distinctive because the upper leg is turned outwards. As a result, the children tend to walk stiffly, with difficulty, and with their legs apart and with bent knees (horse riding stance). In the beginning the muscles are clearly visible because of the loss of subcutaneous fat: the legs look muscular. Later, also the muscle mass will diminish. The shoulder blades are prominently visible: they stick out. Due to arthritis the movement of the joints becomes more difficult, also in the ankles, wrists, shoulders and hips. The joints tend to become painful as a result. A shortening of (one of) the neck muscles may occur, and many children develop a slightly hollow back.

In the final stages children may experience arthritis complaints as a secondary symptom.

atherosclerosis 
Changes in arterial blood vessels and in all other organs occur due to the progressing atherosclerosis, resulting in problems of blood circulation and hardening of connective tissue in the body.

heart and blood vessels 
Initially, Progeria patients do not experience problems with the heart or blood vessels. Blood pressure is also normal during the first years. As from the fourth year, usually between the sixth and eighth year, a heart murmur may be detected. Between the sixth and eighth year children can develop shortness of breath, with increased blood pressure. In some cases, X-rays may show a slight enlargement of the heart. Angina pectoris often occurs, as does atherosclerosis. The vascular problems can arise anywhere in the body: tightness of the chest and respiratory difficulties occur, and also cerebral infarctions may be caused by the arteries silting up. Some patients restore completely, but others have lasting complaints after a cerebral infarction.

To lower the risk of blood circulation problems, some doctors find it advisable to prescribe a low daily dosage of aspirin.

other symptoms 
- Nearly all Progeria patients have a high, shrill voice 
- Another symptom is irregular teeth. The teeth and molars do not have sufficient room in the jaw to grow neatly aligned. Teeth and molars are late in breaking through: in most patients the first teeth break through somewhere between 8 and 24 months. Tooth decay is very common. Brushing teeth is difficult in such a small mouth, but even children that brush their teeth well generally experience more tooth decay than average. To date there is no convincing explanation for this phenomenon. 
- Hearing problems are not found in Progeria children. Even at an older age their hearing functions adequately. Also cataract is found only very seldom in Progeria patients. 
- Though some Progeria children have regularly recurring bronchial infections and ear infections, research does not show any deviations in these parts of the body. 
- The genitals of Progeria boys are described in the literature to be normal. The testicles descend into the scrotum normally. There are no male Progeria patients known that have fathered a child. Female Progeria patients likewise have normal sexual organs. Development of the breasts, however, is absent. Additionally, there is no armpit- or pubic hair. Menstruation only rarely starts for older Progeria girls. In research literature, one girl is mentioned that experienced her first period at the age of 14. In addition, there is also mention of a 32 year-old woman with a non-classical case of Progeria, who started menstruating at the age of 12, and gave birth to a healthy child at the age of 23. These, however, are exceptions: generally Progeria children never go through puberty. 
In the medical literature, of all the Progeria children, only two children have gotten cancer.


In 62 scientific reports, the mental development of Progeria patients is explicitly mentioned. The intelligence of Progeria patients can be considered normal. There is no indication of specific behavioural problems. The children are often remarkably alert, active, optimistic and cheerful.

[1] Prof.Dr.R.C.M. Hennekam –Hutchinson-Gilford Progeria Syndrome; Review of the Phenotype. American Journal of Medical Genetics PartA 140A:2603-2624. May 2006