Hajdu-Cheney Syndrome: Causes, Symptoms & Treatment

Hajdu-Cheney syndrome is a rare bone disorder. It appears to be caused by a genetic mutation that is inherited in an autosomal dominant manner. Standardized treatment measures have been scarce because of the limited number of cases.

What is Hajdu-Cheney syndrome?

Osteolysis is the medical term for an active dissolution of bone tissue. Human bones are a living organism that undergoes changes and remodeling processes throughout life. Osteolysis is thus, in moderation, a physiological process within the framework of normal bone remodeling that reduces bone tissue that is no longer under stress and thus adapts it to its functional requirements. In the context of various diseases, however, osteolysis also has pathological significance. This is the case with Hajdu-Cheney syndrome. This is an autosomal-dominant inherited acroosteolysis, also known as familial idiopathic acroosteolysis or hereditary idiopathic osteolysis type VI. The rare hereditary disease locally degenerates bone tissue. Worldwide, only about 50 cases have been reported since its initial description. Due to the small number of cases, the syndrome has not yet been conclusively researched. This is especially true for the etiology. The U.S. radiologist William Cheney first described the syndrome in the 20th century in a Michigan family. The Hungarian-British radiologist Hajdu described the syndrome shortly thereafter and, along with Cheney, became the namesake of the disorder.

Causes

The cause of Hajdu-Cheney syndrome is thought to be in the genetic material. Scientists hypothesize a mutation that affects bone resorption activity. Which genes mutate as part of the syndrome remains unclear. In addition to the symptom of progressive bone loss, patients with Hajdu-Cheney syndrome usually present with severe short stature. The mutated gene thus not only causes misdirected bone resorption, but apparently a fundamentally defective bone structure. Familial clustering has been observed in the cases documented so far. The family history suggests an autosomal dominant inheritance for the disease. In the family of first description, the mother showed acroosteolysis symptoms, Worm’s bones in the majority, and hypoplasia of the mandible, as did four of her children. Despite the clear family connections of the initial description, cases of spontaneous new mutation were also documented. Thus, in addition to endogenous factors, exogenous factors are probably relevant to pathogenesis. Which exogenous factors could cause new mutations is so far in the dark.

Symptoms, complaints, and signs

Hajdu-Cheney syndrome manifests as short stature associated with progressive degeneration of the phalanges and crowded metacarpals. The cranial sutures show no ossification. The frontal sinus is not created. In addition, there is an elongation of the saddle of the Turk. As the disease progresses, the basilar artery becomes more compressed. This compression can result in a life-threatening condition. The ears of affected individuals usually show abnormally large ear lobes. Furthermore, the ears are one level lower than usual. In addition, a particularly broad nose catches the eye. In the course of the disease, the alveolar processes degenerate bit by bit, which explains the early tooth loss of the patients. In the course of the disease, osteopenia causes scoliosis in the sense of a bending of the spine. These main symptoms are usually associated with accompanying symptoms. For example, some affected persons show kidney symptoms such as cystic kidney in addition to the bone symptoms. In addition, other organ systems may be affected by the disease. In addition to congenital heart defects, hydrocephalus in the sense of hydrocephalus may be present. In addition, the liver and spleen may be enlarged. Cleft palate has also been documented in some cases. The general condition of the patients is characterized by feelings of weakness. Bone fractures are common.

Diagnosis and course

The first signs of Hajdu-Cheney syndrome usually do not manifest in childhood. Thus, in many cases, the diagnosis is not made until adolescence. Early symptoms include primarily pain in the hands. In the course of diagnosis, the family history plays an overriding role, since in most cases an autosomal dominant inheritance forms the background of the disease.If Hajdu-Cheney syndrome is suspected, the physician usually orders a bone density measurement in the form of osteodensitometry. This procedure provides evidence of extreme bone loss. Since no causative gene has yet been identified, molecular genetic tests to detect the disease make little sense. Nevertheless, they can be ordered for research purposes. The prognosis for patients with Hajdu-Cheney syndrome depends partly on the time of diagnosis and partly on the accompanying symptoms.

Complications

Due to Hajdu-Cheney syndrome, the affected person suffers from various conditions that usually affect the growth of the bones and thus the entire body. In most cases, there is a short stature. This field formation can lead to teasing or bullying, especially in children. Furthermore, compression of various bones occurs, which can lead to life-threatening conditions. The position of the ears is also unusual, although this does not lead to hearing problems. Furthermore, it is not uncommon for patients to suffer from kidney problems and heart defects. Due to the heart defect, the affected person can suffer cardiac death in the worst case and die as a result. The spleen and liver are also enlarged and can displace or squeeze other organs inside the body. It is also not uncommon for a cleft palate to occur, making the affected person’s daily life more difficult. Fractures continue to occur very rapidly. There is no causal treatment for Hajdu-Cheney syndrome. For this reason, mainly the pain is treated, with no further complications. The life expectancy of the patient is reduced due to Hajdu-Cheney syndrome. It is not uncommon for the child’s parents or relatives to also suffer from psychological symptoms and require appropriate care.

When should you see a doctor?

Hajdu-Cheney syndrome cannot be completely treated because it is a genetic disorder, so causal therapy is not possible. However, a doctor should still be visited regularly to avoid further complications in the patient. The visit to the doctor is necessary if the patient suffers from short stature and various deformities on the body. Also, degeneration on the finger bones may indicate Hajdu-Cheney syndrome and should be examined. Furthermore, very large ear lobes also indicate the syndrome. In some cases, the disease is associated with skin complaints, which should also be examined by a physician. It is also advisable to examine the internal organs, as kidney problems or a heart defect can often occur. The spleen and liver should also be examined regularly. Since Hajdu-Cheney syndrome can also cause severe psychological distress in the relatives or in the parents, a visit to a psychologist is also advisable.

Treatment and therapy

To date, Hajdu-Cheney syndrome has only been superficially studied. Because only 50 cases have been documented to date, the overall research situation is substandard. Because of the severely limited number of cases, no standardized treatment options exist to date. On an experimental basis, incipient osteoporosis can be treated with bisphosphonates. Causative treatment options do not exist, as the cause of the disease corresponds to a genetic mutation. Such a mutation cannot be reversed. Moreover, because the causative gene has not even been identified, no causal treatment could be developed even with the approval of gene therapy approaches. Against this background, patients are treated purely symptomatically. This treatment may encompass the supportive administration of analgesics in cases of severe bone pain. Special therapeutic measures must be taken, especially in patients with additional cardiac or renal symptoms. In these cases, invasive treatment steps are required. In addition, patients must be examined regularly for vascular compression to identify life-threatening conditions in a timely manner. Surgical interventions to relieve compressed vessels are mandatory.

Outlook and prognosis

The long-term prognosis of Hajdu-Cheney syndrome in terms of life expectancy is not entirely clear because not much empirical data are available. It is an extremely rare genetic disorder that is usually inherited in an autosomal dominant manner.In total, only 50 cases have been reported worldwide. The underlying genetic defect is unknown. It is also suspected that many cases are due to new mutations and therefore occur sporadically. The disease is rarely diagnosed in childhood. The first signs are often severe pain in the hands caused by severe bone loss (osteoporosis). Early-onset osteoporosis can be treated well with biphosphonates. However, the cranial sutures do not ossify, the frontal sinus is absent, and the sella turcica (Turkish saddle) is elongated. Overall, as the disease progresses, this can lead to compression of an artery in the brain (basilar artery), which is often fatal. In a few cases, cystic kidneys, congenital heart defects, cleft palate, hydrocephalus, or enlargement of the liver and spleen have also been observed. These additional symptoms also have a significant impact on the life expectancy of affected individuals. Eventually lethal renal failure or heart failure may develop during life. Prenatal and early infant deaths are also likely due to the occasional occurrence of hydrocephalus. Most importantly, patients’ quality of life is severely limited because of their physical weakness and frequent bone fractures.

Prevention

Prevention measures for Hajdu-Cheney syndrome do not yet exist because of limited research.

Follow-up

Because there are no standardized treatment options for Hajdu-Cheney syndrome to date and all affected individuals are treated purely symptomatically, there is also no standardized plan for follow-up care. This is therefore also based on the symptoms present and the therapies prescribed by the physician. However, regular check-ups of the vessels with regard to possible compression are enormously important for all patients. Thanks to these checks, life-threatening conditions can be detected and compressed vessels can be treated surgically. Unfortunately, as the disease progresses, heart failure or even renal insufficiency may develop. Early symptoms of the latter are excessive thirst and frequent urination. Tiredness, loss of appetite, reduced performance, shortness of breath or even water retention, on the other hand, would be an indication of incipient heart failure. In both cases, a doctor should be contacted immediately. Even without symptoms, regular blood tests for heart failure biomarkers, urea and creatinine are just as important for early detection as urine tests and a diagnosis of the heart by ECG. In addition to drug therapy, patients also have access to acupuncture, aromatherapy and natural remedies. However, the latter may only be taken after prior consultation with the attending physician due to possible interactions. For bone and joint pain, zinc and omega-3 fatty acids are helpful, as are rest and bed rest in acute cases. A change in diet to raw vegetables and lean meats combined with dietary supplements can also be supportive.

What you can do yourself

Individuals diagnosed with Hajdu-Cheney syndrome can take some steps to support treatment. In consultation with the doctor, natural remedies can be used. For example, the natural remedies comfrey, St. John’s wort, and astaxanthin help with severe joint pain. Homeopathy offers preparations with African devil’s claw and frankincense, which have a pain-relieving effect and prevent inflammation in the area of joints and bones. Omega-3 fatty acids and zinc are also proven remedies for bone and joint pain. If any discomfort or unusual symptoms occur as a result of taking them, the appropriate physician must be informed. Furthermore, Hajdu-Cheney syndrome can be treated by changing lifestyle habits. The doctor will normally suggest a diet of raw foods and lean meats, often combined with dietary supplements and avoidance of stimulants such as alcohol and nicotine. For acute bone pain, rest and bed rest will help. The patient can cool the painful areas with a curd or cabbage compress or massage them. Methods from Chinese medicine as well as acupuncture and aromatherapy can also help against chronic pain under certain circumstances. Since the disease can take a severe course despite all measures, psychological therapy should be used to accompany medical treatment.