Johanson-Blizzard syndrome is the name given to a hereditary disease that is rare. Affected individuals suffer from developmental abnormalities of the pancreas, scalp and nose.
What is Johanson-Blizzard syndrome?
Johanson-Blizzard Syndrome (JBS) is a rare inherited disorder that can sometimes be fatal. The syndrome is also considered ectodermal dysplasia and is classified as a pancreatic disorder. In addition to developmental abnormalities of the pancreas, head and nose, hearing problems, short stature and reduced intelligence also occur. The syndrome was named after the American pediatricians Ann J. Johanson and Robert M. Blizzard. The two physicians described the disease for the first time in 1971. The Johanson-Blizzard syndrome is considered a very rare disease. Thus, only about 30 cases are known to date.
Causes
Inheritance of Johanson-Blizzard syndrome is autosomal recessive. In most patients, a mutation at the UBR-1 gene, located on chromosome 15, is the cause of the onset of the disease. UBR 1 encodes a ubiquitin ligase. Ubiquitins are proteins expressed in eukaryotic organisms. They are important for the post-translational modifications of other proteins, the labeling of which occurs during their degradation. Furthermore, UBR 1 plays an important role in cell growth regulation of the pancreas. If a mutation of the UBR 1 gene leads to Johanson-Blizzard syndrome, this results in disturbances or interruptions in the synthesis of ubiquitin ligase. In healthy individuals, a greater amount of UBR 1 is produced within the pancreatic ducts than is produced in other cells of the body. Reduced production of ubiquitin ligase causes dysfunction of the ubiquitin-proteasome complex, which in turn results in chronic inflammation of the pancreas. In this process, the organ stroma is replaced by connective tissue and fat. At the same time, defects occur in the supply of the acini as well as the islets of Langerhans. Furthermore, a failure of apotosis in damaged cells and a defective production of proteins take place. This process may also occur in tissues considered susceptible to improper UBR-1 expression. These primarily include the central nervous system, tooth formation, skeletal muscle innervation, and the cranial region.
Symptoms, complaints, and signs
Johanson-Blizzard syndrome includes a variety of complaints and disorders. The main symptom is considered to be exocrine pancreatic insufficiency. This is associated with a deficiency of trypsin, trypsinogen, lipase as well as other components of the pancreatic secretion, which in turn results in malassimilation. This means that the patient is not able to use the substrates that he/she absorbs from food. In some cases, complete fatty degeneration of the pancreas occurs, the progression of which can sometimes even mean death. Not infrequently, Johanson-Blizzard syndrome also causes diabetes mellitus. Other endocrine disorders that may be considered are pituitary insufficiency, growth hormone deficiency, and hypothyroidism of the thyroid gland. Due to the growth disorders, affected individuals suffer from short stature. Also among the typical features of Johanson-Blizzard syndrome are malformed nostrils. Thus, in some patients, the muscles as well as connective tissue and cartilage on the nose are completely missing. As a result, the patient’s nose takes on an unusual appearance. In addition, many JBS patients are affected by underdevelopment, which varies from individual to individual. There are also individual cases of normal intelligence. Often, affected individuals with JBS also suffer from sensorineural hearing loss in both ears. This is due to cystic changes in the cochlea as well as in the organ of balance. Changes in the temporal bone further promote hearing loss. Craniofacial dysmorphia is also typical of Johanson-Blizzard syndrome. These include a thin scalp, defects in the scalp ridge, and irregular hair growth. The absence of eyebrows and eyelashes, flattened auricles, a domed forehead, an undersized lower jaw, and the absence of permanent teeth are also known external features. In some cases, other organ systems also suffer from Johanson-Blizzard syndrome.The most common disorders include low birth weight, failure to thrive, anal atresia, duplication of the vagina and uterus in females, muscle hypotonia, congenital cataracts, and neonatal jaundice.
Diagnosis and course of the disease
Malabsorption syndrome associated with fatty and bulky stools is considered an important clue for the diagnosis of Johanson-Blizzard syndrome. Similarly, short stature is classified as a characteristic symptom of JBS. Thus, diagnosis usually takes place clinically as well as by certain laboratory parameters. A differential diagnosis to Shwachman-Bodian-Diamond-Syndrome (SBDS) as well as to cystic fibrosis can be of importance. Due to a now possible therapy with pancreatic enzymes, the life expectancy of children with the disease has improved. However, this increases the incidence of diabetes mellitus.
Complications
Due to Johanson-Blizzard syndrome, patients mainly suffer from developmental disorders, and internal organs are also affected by this disorder. Usually, the affected person cannot absorb nitrates from food, which leads to deficiency symptoms and often to being underweight. Likewise, diabetes and short stature may occur. It is not uncommon for affected individuals to also suffer from absent nostrils and thus reduced aesthetics. The Johanson-Blizzard syndrome also leads to a reduced intelligence and to a reduced aptitude. It is not uncommon for hearing impairment or eye complaints to occur. Likewise, eyelashes or eyebrows may be missing and there are severe malformations or damage to the teeth. Due to the malformations, children may become victims of teasing and bullying. The patient’s quality of life is significantly reduced by Johanson-Blizzard syndrome. It is not possible to treat Johanson-Blizzard syndrome causally, so for this reason treatment is purely symptomatic. The reduced intelligence can be relatively well limited with the help of therapies. Further complications do not occur. However, life expectancy is usually limited by Johanson-Blizzard syndrome.
When should you see a doctor?
If physical or mental development disorders can be perceived in children, a pediatrician should be consulted. In the case of short stature, deformities or general growth disorders, the signs should be examined by a doctor. Various tests must be performed to clarify the cause. A particular feature of the disease is a malformation of the face. The area of the nostrils is mutated due to the genetic defect and is considered an indication of an irregularity present. Often, tissue, cartilage or muscles are missing from the nasal area, resulting in the visual abnormality. A visit to the doctor is necessary so that treatment can be initiated. If an impairment of hearing or balance is noticed, a visit to the doctor is necessary. If there is any unsteadiness in gait, abnormality in phonation or hearing loss, a doctor must be consulted. If the affected person is missing permanently attached teeth, if inconsistencies of the jaw are noticeable or if eyebrows as well as eyelashes are missing, a doctor is needed to clarify the symptoms. If peculiarities of the female sex are noticed in girls, a doctor should also be consulted. Since Johanson-Blizzard syndrome can lead to premature death of the affected person in severe cases, it is recommended to consult a doctor already at the first indications of irregularities. Only individualized treatment and targeted therapies can improve quality of life as well as prolong life.
Treatment and therapy
Causal treatment of Johanson blizzard syndrome is not possible. For this reason, therapy is limited to alleviating symptoms. The type of symptoms as well as their severity play an important role. For the treatment of pancreatic insufficiency, the enzymatically active substance pancreatin is administered, the extraction of which takes place from the pancreas of pigs. In the case of deformities of craniofacial body regions or on the skeleton, surgical intervention for correction can provide relief. If hearing impairment is present, the use of hearing aids and special training are considered useful. In the case of a deficiency, adapted occupational therapy measures are available, which are specifically aimed at people suffering from Johanson-Blizzard syndrome.
Outlook and prognosis
Johanson-Blizzard syndrome is one of the rarest diseases of all, with only 30 known cases worldwide to date. Johanson-Blizzard syndrome formerly represented a death sentence because it occurred in infants. The numerous consequences of the disease usually made survival impossible. Today, the situation for those affected is somewhat better. However, it is not yet known whether it is actually a hereditary disease of the pancreas. Modern medicine now treats sufferers with pancreatic enzymes. This has improved the outlook. Nevertheless, given the severity and variety of disease symptoms, long survival is unlikely. A problem is that children affected by Johanson-Blizzard syndrome develop diabetes as their life expectancy increases. This usually leads to damage of the pancreatic tissue, similar to cystic fibrosis of the pancreas. Finally, endocrine pancreatic insufficiency occurs. In cases of severe disease sequelae, the prognosis for some of those affected is poor, despite certain treatment options and despite a prolonged life. However, in some cases, symptomatic treatment of Johanson-Blizzard syndrome may be more successful. Depending on the severity, pancreatic insufficiency can be substituted with pancreatin. Surgical correction of head and skeletal deformities is possible today. Hearing aids and hearing schools can provide improvement for hearing loss. Occupational therapy may also be helpful and improve prognosis.
Prevention
Prevention of Johanson blizzard syndrome is not considered possible. Thus, it is a disease that is already congenital.
Follow-up
For the aftercare of Johanson blizzard syndrome, there are no special measures in the context of self-help. Long-term medical treatment is therefore inevitable. Close monitoring is required so that any complications, such as pancreatic insufficiency, are detected quickly. The treatment of such complaints is carried out by means of special medications. Patients must take the drugs according to the specialist’s recommendation. Since the disease is often accompanied by retardation, they often need the support of their parents. If the hereditary disease leads to deformities or malformations, surgical intervention may be required. In everyday life, patients need the support of their family, as they usually have limited intelligence. The doctors are familiar with the possibilities and inform the affected parents about special support for these children. Loving care costs a lot of effort, but provides a better quality of life. There are many learning exercises that can be done at home that train cognitive skills. Occupational therapy applications are available for physical health. Patients and their families also benefit from contact and information exchange with others affected by the disease. Meanwhile, the life expectancy of patients has lengthened: then parents have to expect diabetes mellitus later.
What you can do yourself
Since Johanson-Blizzard syndrome is a hereditary disease, it cannot be treated causally. Likewise, no special self-help measures are available to the affected person in this case, so that this person is dependent on medical treatment in any case. If an insufficiency of the pancreas occurs, it is usually treated with the help of medication. In this case, the affected person must ensure that these medications are taken regularly in order to avoid complications and other complaints. Parents must also ensure that their children take their medication regularly. Deformities and malformations of the skeleton can only be treated by surgical intervention. Since most patients also suffer from reduced intelligence, they are dependent on help from other people and special support in their daily lives. The care of the affected persons must be done lovingly. Parents can also carry out various learning exercises with their children at home in order to promote the development of the affected person. Occupational therapy measures can also be very helpful here. Furthermore, the contact to other affected persons has a very positive effect on the Johanson-Blizzard Syndrome, because it comes to an exchange of information.
