Geroderma Osteodysplastica: Causes, Symptoms & Treatment

Geroderma osteodysplastica is one of the rare genetic diseases. It is characterized by premature aging of the skin and decalcification of the bones. However, life expectancy is not limited.

What is geroderma osteodysplastica?

Geroderma osteodysplastica is a disease of connective tissue and bone. It is hereditary and occurs with a very rare prevalence. Thus, only about one in a million people is affected. The connective tissue ages prematurely. At least it appears aged by its wrinkled and wrinkled appearance due to a malformation. In addition, high grade osteoporosis with frequent bone fractures already occurs in childhood. The leading symptoms of the disease are already indicated in its name. Thus “geroderma” means old skin and “osteodysplastica” bone malformation. The term Bamatter-Franceschetti-Klein-Sierro syndrome is still used as synonyms for these diseases. This name refers to the first discoverers of this disease. Together with the ophthalmologist Adolphe Franceschetti from Geneva, the physician A. Sierro and the human geneticist David Klein, this syndrome was already described in 1950 by the Swiss pediatrician Frédéric Bamatter. Scientists at the Max Planck Institute for Molecular Genetics in Berlin, under the direction of Stefan Mundlos, studied 13 families in which this disorder occurred. Members of these families were particularly common among the Mennonite denomination.

Causes

The cause of geroderma osteodysplastica may be a genetic defect. In many cases, the GORAB gene of chromosome 1 is affected by a mutation. Strangely, however, this mutation is not found in every affected person. The mode of inheritance is autosomal recessive. Recently, patients have also been discovered who have a mutation on the PYCR1 gene of chromosome 17. In this form of the disease, there is a particularly strong clinical overlap of symptoms with Cutis-Laxa syndrome and Wrinkly-skin syndrome. Therefore, it must be assumed that Geroderma osteodysplastica is not a uniform disease, but represents a collective syndrome of several clinically similar diseases. Approximately 13 families were studied in which several cases of the disease occurred in the relatives. Thus, this disease does not occur spontaneously.

Symptoms, complaints, and signs

Geroderma osteodysplastica is characterized by the fact that even newborns have sagging, old-looking skin. This is caused by a defective structure of the connective tissue. The joints are hyperextensible. In addition, growth disorders occur in children. Those affected suffer from short stature. Osteoporosis is particularly pronounced. It occurs generalized over the entire body and causes constant bone fractures. In addition, there is hip dysplasia. The cause of osteoporosis is generalized decalcification processes within the bones. The head exhibits brachycephaly with a protruding forehead. Brachycephaly is manifested by a deformation of the skull, which leads to a so-called short-headedness. The eyes are also affected. Occasionally, microcornea (cornea that is too small) occurs. The cornea is also clouded and glaucoma (glaucoma) may also occur. Furthermore, general developmental disorders are observed. Mental development is usually normal. At times, a mild intellectual deficit may occur. The greatest indication of geroderma osteodysplastica is marked osteoporosis with spontaneously occurring fractures and a lack of open fontanel in the newborn. The life expectancy of affected individuals is not limited. In the course of life, even the frequency of fractures decreases. There is also improvement in other symptoms.

Diagnosis

Geroderma osteodysplastica is not easily differentiated from cutis laxa syndrome, wrinkly skin syndrome (WSS), and de-Barsy syndrome in terms of differential diagnosis. However, the unique feature of geroderma osteodysplastica is the combination of generalized osteoporosis together with the absence of open fontanel. In contrast to the other syndromes in this group of forms, the physical limitations are not as great. Furthermore, the mental development is usually completely normal.

Complications

As a rule, geroderma osteodysplastica does not result in a reduction in life expectancy. However, the patient suffers from premature aging of the skin, although the bones are also decalcified. Due to an incorrect structure in the connective tissue, it is possible for the affected person to overstroke and thus damage the joints. This increases the risk of accidents, especially in children. It is not uncommon for patients to also suffer from short stature. The skull is deformed and usually relatively short. Due to the deformities, children may suffer from bullying and teasing, resulting in psychological complaints and depression. Developmental disorders also continue to occur, with intellectual dysfunction also occurring. In some cases, the affected person is then dependent on the help of other people or caregivers in everyday life. Due to the discomfort of the bones, spontaneous fractures can also occur, which are associated with very severe pain. Treatment of geroderma osteodysplastica is only symptomatic. Complaints to the eyes can be corrected relatively well, so that no further complications occur. The patient is also dependent on psychological therapies in many cases.

When should one go to the doctor?

In case of growth disorders, changes in bone structure or short stature, a visit to the doctor is necessary. If the child shows developmental disorders in direct comparison with peers, a doctor should be consulted. In case of a learning disability, comprehension problems, a reduction in intelligence, concentration or attention deficits, it is advisable to consult a doctor. If bone fractures of any kind occur more frequently, discussion with a medical professional should be sought. If the joints can be overextended or if pain sets in during locomotion, a visit to the doctor is necessary. Deformities of the skull are considered a concern. If there is a bulging forehead, shortness of the head or visual changes around the eyes, a doctor should be consulted for clarification. If irregularities of the connective tissue can be detected at an early age, the observation should be discussed with a physician. If the child shows behavioral abnormalities, is particularly restless or aggressive, a visit to the doctor is necessary. In case of social withdrawal, tearful or melancholic behavioral traits as well as depressive mood, a doctor is needed. If the child shows contact difficulties, has increased anxiety due to the symptoms, and refuses to participate in sports activities, a doctor’s visit is needed to alleviate the symptoms. If sleep disturbances occur or there are digestive problems or headaches, psychosomatic complaints may be present and need to be investigated.

Treatment and therapy

Treatment of geroderma osteodysplastica is symptomatic. Causative therapy is not possible because it is a genetic defect. However, the limitations are not as great as in many similar cutis laxa syndromes. Only generalized osteoporosis requires constant monitoring and therapy. Here, the administration of biphosphates has been very successful. Of course, the frequently occurring bone fractures must be treated at all times. In the course of life, however, the bone fractures gradually decrease. The bone metabolism normalizes. Eye complaints also require constant control. Here, clouding of the cornea and even the development of glaucoma can occur. Of course, the ophthalmologist must monitor the further development. However, the eye symptoms are not obligatory. The affected person does have progeroid features. However, the aging process does not progress as rapidly as in the case of classic progeria. The wrinkled and wrinkled skin is also not an expression of true aging, but is caused by the malformation of the connective tissue.

Outlook and prognosis

Geroderma osteodysplastica is a disease that is not considered curable. Therefore, the prognosis is not very optimistic. The genetic defect cannot be altered or corrected. Legal requirements prevented any intervention in the genetics of humans according to the current status. For this reason, the treatment of patients is based on the individual symptoms, and not all of them can experience relief. The existing symptoms can also lead to further secondary diseases and trigger emotional problems.Due to the visual aging as well as the limitations of the disease, many patients suffer from mental disorders. These are treatable but usually characterized by a long healing process. Developmental disorders as well as reduced intelligence are possible in geroderma osteodysplastica. Although support programs are created and used, these usually only provide support in coping with everyday life. A cure is not given. The goal is to improve the general well-being and to enable a good lifestyle with the disease. Nevertheless, in many cases daily care by caregivers or relatives is necessary, since no independent lifestyle can be completed. Despite the numerous impairments of the disease and the fact that it cannot be cured, the general life expectancy of those affected is not reduced. Likewise, there is a good prospect of improvement in vision once it has been limited.

Prevention

Human genetic counseling should be sought to prevent geroderma osteodysplastica. Geroderma osteodysplastica is hereditary with an autosomal recessive mode of inheritance. However, the mutated gene is very rare with a prevalence of one in a million. The probability of inheritance of this disease is increased only within consanguineous marriages in affected families. In a recessive inheritance, for marriages in which both partners are gene carriers, the probability for the offspring to be born with this disease is 50 percent.

Follow-up

In most cases of geroderma osteodysplastica, there are no special options for follow-up care. However, these are also not necessary, since the disease cannot be treated completely. If the patient wishes to have children, genetic counseling can also be performed to ensure that the disease is not inherited by potential offspring. Causal treatment is not possible in this case due to the genetic nature of the disease, so that affected individuals are dependent on purely symptomatic therapy for the rest of their lives. In most cases, patients are dependent on taking medication. It is important to ensure that the medication is taken correctly and regularly in order to prevent further complications. The eyes should also be checked regularly to prevent clouding. In the worst case, geroderma osteodysplastica can cause complete blindness of the affected person. However, the life expectancy of the patient is not limited or reduced by the disease. Furthermore, contact with other patients of Geroderma osteodysplastica can be useful. This often leads to an exchange of valuable information, which can make everyday life easier. The support of one’s own family can also significantly alleviate the symptoms.

What you can do yourself

Although patients with geroderma osteodysplastica are visually conspicuous, social withdrawal out of shame is counterproductive. To keep the quality of life as high as possible, sufferers maintain social contacts and engage in normal activities in public spaces. Contacts with other people with geroderma osteodysplastica or similar diseases are particularly helpful in order to share experiences and provide mutual social support. However, it is useful not to spend time exclusively with other sufferers, but also with people without such diseases. With regard to susceptibility to fractures, patients place particular emphasis on accident prevention in everyday life and refrain from risky activities and movements. If fractures do occur, it is important to get enough rest to promote recovery. Physiotherapy exercises to strengthen tendons and muscles are also important, possibly to prevent certain accidents and improve general mobility. Usually, patients with geroderma osteodysplastica are undergoing physiotherapy treatment and are therefore familiar with individually useful exercise options. The strengthening effects of these exercises increase even more if the patient additionally performs them at home on his or her own responsibility. Regular consultation with the physician and physiotherapist is essential.