What is Acrogeria?
If we were to understand the literal meaning of the word it would mean- aging of the tips and that’s exactly what happens in Acrogeria. Acrogeria is one of the very few premature aging diseases that are present in the patients congenitally and it affects the skin on the hands and legs. The other two known premature aging conditions are Werner’s Syndrome and Progeria. This occurs at very early ages of the patient’s life. Acrogeria is otherwise known as Mategeria and Acrometageria. Acrogeria is a non-progressive condition and isn’t one that’s fatal. The rapid aging is seen not only in the skin, but affects other tissues as well.
What Causes Acrogeria?
As with most of these extremely rare disorders, the exact cause of Acrogeria is unknown but from the studies, the disease is shown to have genetic causes but not familial ones.
The first recorded case was present in two siblings which indicate that there could be inheritance factor involved, however subsequently most of the noted cases of Acrogeria have been constantly sporadic in nature; with no vertical transmission involved.
The rarest among these that did involve inheritance showed that the inheritance was both of autosomal dominant type and autosomal recessive type.
Consanguinity (marrying within the family-such as among cousins) has been noted to have a role in the occurrence of Acrogeria.
What Happens in Acrogeria?
Acrogeria- the quick ageing of tissues- is said to occur due to mutations (random alterations of the structure and functions of the affected genes which then multiply and spread the mutation; this is a completely random event that may or may not be triggered by factors such as environmental causes (exposure to toxins), etc.) of the COL3A1 gene that determines the strength and elasticity- firmness of the skin tissue. Each cell present in the human body has 23 pairs of chromosomes-contribution to each pair is from the mother and the father. This mutation then may or may not be inherited by the following generations. These mutations when observed under culture show that there are a reduced number of messenger RNA (Ribonuclease) that are supposed to control the aging in the fibers that the skin is made of- Type I and II collagen fibers.
So now that these mutations are present, the elasticity and integrity of the skin tissues are lost- which is usually maintained by collagen fibers. But due to triggers for early aging, the skin present especially on the legs and hands become fragile and break down. This happens since the fat tissue beneath the skin in these areas- known as the adipose layer- gets atrophied and is lost. So now there’s no base to keep the skin firm and intact. This occurrence is called subcutaneous atrophy- atrophy under the skin.
Incidence of Acrogeria
Only forty known cases have been noted down in medical literature. From the very few available data, it can be assumed that females are affected at a higher rate than males but the lack of extensive research makes this information inconclusive.
Signs and Symptoms of Acrogeria
As in most diseases, it must be noted that not every patient shall display every sign and symptom of the Acrogeria. It varies from patient to patient and that it’s very rare to have a typical presentation featuring all the said symptoms.
General Appearance: The young humans affected by Acrogeria are generally seen to have an aged appearance. Imagine a small child having fine lines on the skin and wrinkles just like an old person. Apart from this exterior, a very notable feature is how small their hands and feet are- which is very apparently disproportionate to the growth and development of the rest of their bodies. The cheeks are hollow and look like they’ve sunken. The eyes are big and protruding like that of an owl. The lips are very thin and evidently atrophying.
Skin Lesions: The most common symptom of Acrogeria and the most prevalent one is the advanced aging that’s present on the tips of the fingers and toes.
Characteristically withered and wrinkles skin resemblant of old age is seen. The skin is said to be like that of the texture of a parchment. It is thin and extremely fragile. Veins are prominent and distinctive under the skin of the affected children because of the lack of fat tissue. Skin all over the body can also be affected in some cases- like the chest, etc.
Rarely, ulcers can be formed on the skin.
A reddish purple cluster of small blood vessels- capillaries- can be seen under the skin in some cases- a phenomenon known as Telangiectasia.
There is hyperpigmentation present irregularly which is the increased color of the skin which is probably present as patches of hyper-colored skin. Along with this fine hair is seen to be present on the skin in almost all the cases of Acrogeria.
Symptoms Of Acrogeria That Affect The Skeletal Structure: The Kids who have been affected by Acrogeria have extremely flexible joints- and this symptom is called Hyper-flexibility. If a closer look is taken at the ridges of their nose, it’s seen to have assumed a convex shape- which shows some sort of bending has happened. This causes the patient to have what is called a beaked nose. These kids have undersized jaws that are usually common in children below 2 years of age but resolves naturally with development but not in this disease. Why this is of concern is because it causes overcrowding of the teeth in the oral cavity which in the early ages can cause poor feeding of the children- which leads to malnutrition and stunted growth. This feature is called micrognathism.
Another skeletal feature that’s seen in Acrogeria is scoliosis, which is the abnormal bending of the spine which causes it to be curved to the side. Some cases may have skeletal dysplasia, which is a condition where there is a presence of some abnormal cells that are present- in this case of the osteocytes ie bone cells.
Mental Abnormalities: it is due to stunted growth and development, frequently Acrigeria kids are seen to have stunted mental development and have a lesser intelligence quotient, memory, and problem-solving skills that are expected from the children their age.
Diagnosis of Acrogeria
Since there are no molecular workups that can aid in the diagnoses of Acrogeria, it’s mainly and exclusively just a clinical diagnosis- a proper history including family history and clinical examination. Sometimes X-rays may be done but only to look for bone and cartilage involvements along with the skin lesions, but this isn’t diagnostically valuable to the physician.
Biopsy of the skin shows that the fat under the skin- subcutaneous tissue has been completely replaced. In its place connective tissue is present.
Treatment of Acrogeria
As of now, there is no known treatment for Acrogeria. However, this isn’t a major problem considering that Acrogeria has an excellent prognosis. Families need to be supportive and counseling is provided for the affected before they plan on having children or to those parents who have affected children.
Differential Diagnosis & Prognosis of Acrogeria
Acrogeria can be misdiagnosed as any of the following conditions characterized by premature aging.
- Hutchinson- Gilford Progeria Syndrome- similar symptoms but with normal intelligence but reduced life spans.
- Werner Syndrome- the noticeable difference is that this disease is only identified by the 30s or 40s age in the patients showing greying of hair or alopecia.
Both the above syndromes have many symptoms in common with Acrogeria including the loss of subcutaneous tissue which is subsequently replaced with connective tissue- thus causing prominent veins to be visible in all areas of the body. The beaked nose, owls like eyes and small jaws are also seen in all three cases. All of these conditions show signs of stunted growth and development such as short stature and the growth is stopped as soon as they enter puberty.
Since they have many similar features present, and the other two are relatively common compared to Acrogeria, the only way to reach a diagnosis of Gottron Syndrome is by watching out for the prognosis of the disease. Prognosis is a term used to explain the positive progress of a disease- such as how a disease responds to the treatment used. Since no treatments work on this disease, a good prognosis would mean that there is very less worsening or progression of the disease- and that after a certain stage no new symptoms occur and that the ones present are manageable.
In case of Acrogeria, the prognosis is seen to be far better when compared to both Werner’s Syndrome and Hutchinson- Gilford Syndrome.
While there are no known ways to prevent the occurrence of this very rare disease, genetic counseling can be seen to help prevent voluntary transmissions of the disease to the future generations.