Acrodysostosis is a rare genetic disorder characterized by skeletal malformations, growth delays, short stature, and distinctive facial features caused, in part, by underdeveloped (hypoplastic) certain facial bones, particularly those in the middle portion of the face. A characteristic symptom is abnormally small hands and feet with short, stubby fingers and toes that may affect all or some of the fingers and toes. Some affected children have varying degrees of intellectual disability; in other children intelligence is unaffected. Some children experience resistance to certain hormones, which means that the tissues of the body do not respond to the hormone in question despite normal or high activity levels of the hormone. Acrodysostosis may be caused by mutations in the PRKAR1A gene (type 1) or the PDE4D gene (type 2). These mutations usually occur sporadically without a positive family history; mutations in PDE4D can be inherited in an autosomal dominant manner. Additional forms of acrodysostosis likely exist; caused by as-yet-unidentified gene mutations.
Acrodysostosis is an extremely rare disorder that is present at birth (congenital). It leads to problems with the bones of the hands, feet, and nose, and intellectual disability. The skeleton is made up of 206 bones in the adult and contributes to the form and shape of the body.
Causes
Acrodysostosis is caused by a mutation in either the PRKAR1A gene or the PDE4D gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain.
In many cases, these gene mutations are believed to occur as new (sporadic or de novo) mutations, which means that a gene mutation has occurred at the time of the formation of the egg or sperm for that child only, and no other family member will be affected. The disorder is usually not inherited from or “carried” by a healthy parent. However, dominant inheritance (where a trait is transmitted from either an affected mother or father to their child) has been documented in acrodysostosis type 2.
Genetic diseases are determined by the combination of genes for a particular trait that is on the chromosomes received from the father and the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the gender of the resulting child.
Investigators have determined that the PRKAR1A gene is located on the long arm (q) of chromosome 17 (17q24.2) and that the PDE4D gene is located on the long arm of chromosome 5 (5q11.2-q12.1). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”.
The PRKAR1A and PDE4D genes both create (encode) proteins that play a key role in the cAMP signaling pathway. A signaling pathway is the series of chemical processes by which certain cell activities are controlled and managed. The cAMP signaling pathway is essential for the proper formation of bone (skeletogenesis) and the action of many hormones including the parathyroid hormone and the thyroid-stimulating hormone. Mutations in these genes modify the function of the specific protein product, which ultimately leads to the symptoms of acrodysostosis.
Diagnosis
A diagnosis of acrodysostosis is based upon the identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation, and a variety of specialized tests including X-rays.
Clinical Testing and Workup
Prenatal fetal ultrasonography, an exam in which reflected sound waves create an image of the developing fetus, may potentially reveal intrauterine growth retardation and short long bones that are compatible with the diagnosis of acrodysostosis. However, no specific antenatal signs have been isolated.
Some symptoms of acrodysostosis may be obvious at birth such as characteristic facial features and growth retardation. Traditional x-ray studies may reveal abnormally short bones in the hands and feet and premature fusion of the end portions (epiphyses) of certain bones of the hands, feet, and elbows. The appearance of spots on the epiphyses (stippling) may also be detected by traditional x-ray.
In some cases, molecular genetic testing can confirm a diagnosis of acrodysostosis. Molecular genetic testing can detect mutations in one of the two specific genes known to cause the disorder but is available only as a diagnostic service at specialized laboratories.
Treatment
It is initiated in a well-coordinated manner by the team in the following ways:
- Pediatricians: They are child specialists and take care of the overall health problems of the child.
- Orthopedician: Skeletal deformities and malformations are taken into consideration by orthopedics.
- Pediatric endocrinologists: Hormonal imbalance is diagnosed and treated accordingly under their supervision.
- Orthopedic surgeons: They perform bone-related surgeries which can be a part of the treatment of Acrodysostosis.
- Orthodontists: They take care of the teeth and related abnormalities such as malocclusion and malalignment.
- Neurologists: Any abnormality or disorder related to the child’s nervous system is taken into consideration.
- Ophthalmologists: Visual abnormalities are treated by ophthalmologists.
The treatment of acrodysostosis is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, specialists who diagnose and treat skeletal abnormalities (orthopedists), specialists who diagnose and treat hormonal imbalance (pediatric endocrinologists), orthopedic surgeons, specialists who diagnose, prevent, and/or treat abnormalities of the teeth (orthodontists), neurologists, ophthalmologists, physical therapists, and other health care professionals may need to systematically and comprehensively plan an affected child’s long-term treatment.
There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with acrodysostosis.
Specific therapies for the treatment of acrodysostosis are symptomatic and supportive. Surgery may be performed to correct specific abnormalities such as underdeveloped (hypoplastic) and/or abnormally prominent jaws (prognathism). In some cases, dental braces may be required to correct misaligned teeth (malocclusion). In addition, in some cases, physical therapy may also be required. Thyroid hormone supplementation and vitamin D supplements may contribute to improving growth and preventing obesity.
Early intervention is important to ensure that children with acrodysostosis reach their full potential. Special services that may be beneficial to affected children may include special remedial education, social support, and/or other medical, social, and/or vocational services.
FAQ
How to prevent Acrodysostosis?
Acrodysostosis is a genetic disease that has an autosomal mode of transmission. It is present in an individual congenitally and is a lifelong disease. It can occur in any individual be it male or female. No external factors are involved in the occurrence of this disorder in any individual. These are the genes only that are responsible for such conditions. Hence, the prevention of Acrodysostosis is not possible.
Acrodysostosis is a rare disease that is present in an individual from birth. The prevention of this disease is not possible since the cause is related to genetic mutations.
What to do when Acrodysostosis?
Acrodysostosis occurs usually in the sporadic form. It is present in any individual since birth. The disease is related to the mutation of genes and is linked to the autosomal dominant mode of transmission. When an individual develops this rare condition, the first important thing that should be done is to approach a well-specialized team of doctors who can do the treatment in a coordinated way. Such a team of specialists should include a pediatrician, orthopedic surgeon, neurologist, orthodontist, ophthalmologist, and physical therapist. A combined effort of the whole team can treat the disease effectively.
Since Acrodysostosis is a genetic disorder, its prevention is not possible. However, it is important to consult a well-specialized neurologist for a pro[er diagnosis and an adequate treatment plan.
Can Acrodysostosis go away on its own?
Acrodysostosis is related to the genetics of an individual and is inherited through an autosomal dominant mode of transmission. It is present congenitally and its development remains unaffected by any other factors. This disorder cannot get resolved spontaneously and needs to undergo treatment under the supervision of well-coordinated efforts of a specialized team of doctors. It is a lifelong condition and cannot be cured. Control and management of the related symptoms can be done only.
What to eat in Acrodysostosis?
Diet is always linked to all health issues directly or indirectly. In the case of Acrodysostosis, the diet has been known to play a key role in the control and management of the condition. Some of the food items which need to be consumed while suffering from Acrodysostosis include the following:
- Sources of healthy carbohydrates: These include staples including whole grains, cereals, maize, rye, or starchy carbohydrates like potato, yam, etc.
- Sources of proteins: Meat, fish, eggs, milk, etc. are some sources of protein that need to be incorporated into our daily diet.
- Lean proteins: These include chicken, legumes, beans, lentils, etc.
- Sources of Vitamins, minerals, and antioxidants: These include fresh fruits and vegetables which are rich in fiber too.
- Healthy fats: Some important sources are olive oil, sunflower or corn oil, soy, etc.
One should take care of his/her dietary intake when suffering from Acrodysostosis. The disease may be directly or indirectly linked to the diet. Food items such as low fat containing eatables, fresh fruits, and vegetables, whole grains, soy milk, dried fruits, etc. are preferred.
What not to eat in Acrodysostosis?
Certain kinds of food items that need to be avoided in conditions like acrodysostosis include the following:
- Sources of saturated fatty acids: These are the unhealthy fats that provoke risks of obesity and related disease. Examples are butter, ghee, lard, etc.
- Foods having salt content: Salt levels in the regular diet of an affected individual should be kept up to a normal level. Any increase in salt intake may cause risks of several health problems.
- High sodium content food items: These include sauces like soy sauce or fish sauce.
- Food containing high levels of sugar: Certain food items need to be avoided in this category. These include candies, cookies, cakes, chocolates, etc.
proper intake of diet may play an important role in the control and management of the disease, not directly but in an indirect way. Hence, it is important to know about certain food items to be avoided in this condition and those include unhealthy fats, excessive salt intake, foods rich in high sodium levels, high sugar food items, etc.
What are the side effects of Acrodysostosis treatments?
The treatment of Acrodysostosis mainly involves the symptomatic and supportive way based on the symptoms being shown in the affected individual. However, some side effects may be observed during the treatment of Acrodysostosis. These include the following:
- Nausea
- Feeling sick
- Fevers and chills
- A severe form of headaches
- Bad taste in the mouth
- Infection in the ear
- Visual disturbances
The treatment of Acrodysostosis is mainly based upon symptomatic and clinical evaluation. However, there are some side effects commonly associated with the condition. Those include nausea, headaches, bad taste in the mouth, etc.
Should I go to urgent care for Acrodysostosis?
Acrodysostosis is a rare genetic abnormality that develops in an individual as a result of mutations in the specific genes and shows the autosomal dominant mode of transmission. It shows symptoms like skeletal malformations, facial dysplastic abnormalities, short stature, small limbs with small extremities, mental disabilities, and hormonal imbalance.
These symptoms are not self resolvable and hence need medical attention and care on an urgent basis. The treatment cannot cure the disease but enables the affected individual to lead to a normal and good quality of life.
Acrodysostosis is present congenitally and its development remains unaffected by any other factors. Hence, it needs to undergo urgent medical care and treatment under the supervision of well-coordinated efforts of a specialized team of doctors and cannot resolve itself.
How long does it take to recover from Acrodysostosis?
Acrodysostosis is a lifelong abnormality that is present in the individual since birth. The disease cannot be cured and the affected individual remains with the symptoms till the end of his life. Symptomatic and supportive treatment is possible which ensures a better quality of life for the patient.
Acrodysostosis is a lifelong abnormality that cannot be cured. The treatment only ensures a better quality of life for the patient and enables him to lead a normal healthy life.
What is the price of Acrodysostosis treatments in India?
The treatment of Acrodysostosis is based upon symptomatic and supportive treatment therapies. It does not involve a single specialty but it is a combined and coordinated effort of multiple specialties. The treatment is lifelong and so is the expense related to it. Hence, the price for the overall treatment modalities sums up to a bigger amount. In other words, it can be said that Acrodysostosis treatment is quite expensive in India.
Acrodysostosis is associated with a treatment that is continued throughout the life of an affected individual. The overall treatment modalities consist of multiple specialties treatments and are quite expensive.
Physical Exercises for the people suffering from Acrodysostosis
Physical exercises are necessary for people suffering from Acrodysostosis. Lack of activities and movement in such patients may even worsen the symptoms by causing obesity or weight gain. These are not favorable for conditions of short stature, skeletal malformations, facial deformities, etc. Hence, it is important to implement exercises regularly to prevent such complications. Some of them include:
- Low or moderate-intensity cardiovascular exercises: These Are important to maintain healthy body weight as abnormal weight may induce several health risks. Swimming, cycling, and running are commonly preferred.
- Walking: This is important as regular walking improves blood circulation and the overall health of the affected individual. One should walk for at least 30 minutes to get proper health benefits.
- Various yoga poses: Several yogas including pranayam can effectively help in maintaining a healthy state of mind as well as body.
- Regular exercises: These include the normal form of exercises which we can do ourselves in our home.
It is important for an individual suffering from Acrodysostosis to implement regular physical activities and mild exercises on a daily basis. However, severe forms of exercise should not be preferred as they may increase fatigue, weakness, and lethargy.
Which is the best medicine for Acrodysostosis?
Acrodysostosis is not a single disease abnormality but is a combination of multiple abnormalities. Hence, the treatment methods preferred in such conditions involve symptomatic and supportive therapies based upon the symptoms being shown in the affected individual. Hence, there is no concept of the single best medicine for Acrodysostosis.
Treatment methods of Acrodysostosis involve symptomatic and supportive therapies based upon the symptoms being shown in the affected individual. However, there is no concept of the single best medicine for Acrodysostosis as the treatment is a combined multispeciality treatment.
Are the results of the Acrodysostosis treatment permanent?
The treatment of Acrodysostosis is based on the symptoms being shown up in the individual. It is a multiple specialty treatment. The results of the treatment are not permanent since the disease is incurable. The outcome that we get out of the combined form of treatment ensures the individual leads a better quality of life.
The results of the treatment of Acrodysostosis are not permanent since the disease is non-curable. The outcome that we get out of the combined form of treatment ensures the individual leads a better quality of life.
What are the alternatives to the Acrodysostosis treatment?
Acrodysostosis is an incurable disease. Symptomatic and supportive treatment are the only possible ways to survive this abnormality. Hence, no alternatives are known so far, as far as the condition of Acrodysostosis is concerned.
Acrodysostosis can only be treated by an application of symptomatic and supportive treatment. This is important so as to ensure a better quality of life. However, no alternatives have been known so far.
Who is eligible for the Acrodysostosis treatment?
Acrodysostosis is a congenital hereditary disorder that can develop in any individual of any age group or sex. The symptoms of the disease cannot be resolved spontaneously and the disease itself is incurable. Hence, it is necessary for every individual suffering from the abnormality to undergo symptomatic and supportive treatment. Hence, every affected individual is eligible for treatment.
Who is not eligible for the Acrodysostosis treatment?
Since Acrodysostosis is incurable, every individual suffering from this rare disorder has to undergo proper treatment under the supervision of a specialized team of doctors of multi-specialty. Hence, anyone who is affected has to undergo the treatment and be eligible for the same.
What are the post-treatment guidelines?
Some of the post-treatment guidelines need to be followed by the individuals suffering from Acrodysostosis. These guidelines include:
- Undergoing regular health checkups to avoid any risks of probable infections.
- Maintaining a healthy well-balanced diet in daily routine including essential nutrients in a required ratio.
- Regular physical activities and low or moderate-intensity exercise forms.
- Keeping consistency in a healthy diet, lifestyle changes, etc.
Acrodysostosis is a congenital hereditary disorder that can develop in any individual of any age group or sex. It is a lifelong abnormality. It cannot be cured and the affected individual remains with the symptoms till the end of his life. Only symptomatic and supportive treatment is possible which ensures a better quality of life for the patient.
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