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What

Hajdu-Cheney Syndrome (HCS) is a rare disorder characterized by acro-osteolysis of various bones in the body.  Acro-osteolysis means gradual breakdown of bone, starting with the extremities and peripheral bones, like fingers and toes.  This breakdown of bones can then lead to other complications, including headaches, infections, fractures, short stature, and other neurologic difficulties. 

Who

This syndrome can affect anyone who has a sporadic genetic mutation that leads to the syndrome.  It can also run in families.  However, it does not seem to preferentially affect persons of any particular ethnicity, race, sex, or nationality.  Unless the diagnosis is suspected because of other family members with the disease, it is often not diagnosed until late adolescence or adulthood, when the manifestations of the disease become more prominent.

Signs and Symptoms

The signs and symptoms of the disease vary depending on the patient's age.  Also, not all patients manifest all the possible findings that have been reported with the disease, making it rather heterogenous in its presentation.  A recent review summarized the characteristics of 57 patients with the diagnosis:  84% of patients had acro-osteolysis, 74% had digit abnormalities, 67% had abnormal dentition, 60% had decreased bone density, 60% had hypermobility of their joints, and 56% had small jaws (micrognathia).  Many of the patients also had problems such as: scoliosis, kyphosis, kidney problems, recurrent infections, abnormal sinuses, and multiple fractures.  These  findings may not be obvious at birth but only become more so as the child grows and has problems such as recurrent infections, poor bone healing, short stature, recurrent headaches, and spinal abnormalities. 

Possible Causes

The underlying genetic abnormality in this syndrome is unknown.  Either it arises because of spontaneous mutations in genes associated with the syndrome, or it runs in families who have mutations in those genes and are transmitting the genes to their children.  When the disorder is familial, it is usually "autosomal dominant."  This means that only one copy of the affected gene is necessary to create the syndrome.  For example, if a father has the disorder then one of his chromosomes carries the mutation.  If the mother does not carry the mutation, then there is a 50% chance that the mutated chromosome gets transmitted to their children and causes the disease.  Notably, there has been no association between development of the syndrome and particular behaviors, medications, infections, or diseases in either of the parents; pregnancy may be completely uneventful, with a relatively normal childhood before the disease manifests itself. 

Diagnosis

 

One set of criteria for diagnosis is as follows:  if the patient is an adult, he or she must have acro-osteolysis plus any 3 of the following:

a. wormian bones (small pieces of bone interspersed in the natural sutures of the skull)

b. platybasia (in which the base of the back of the head has an altered shape, often causing headaches)

c. premature loss of teeth, micrognathia (small jaw)

d. coarse hair or facial features

e. midfacial flattening

f. short stature (<5^th percentile)

If the patient is a child, the criteria are the same, although signs or symptoms may not yet manifest acro-osteolysis if he or she is very young.  Diagnosis is made based on a careful family history, multiple X-rays indicating abnormalities in the bones, and careful physical examination. 

Treatment

 

Treatment remains largely symptomatic.  Because the specific cause of the disease is not well-understood, there remains no therapy which can cure the disease.

Therefore, pain (which may manifest as headaches, joint pain, or back pain) is managed symptomatically, and patients learn to minimize risk for falls and fractures, which can be devastating.  These patients should be managed by a team of subspecialists, including geneticists, endocrinologists, and orthopedics. 

A very recent case report outlines a strategy for treatment which seems to minimize progression of the acro-osteolysis.  This strategy (only attempted in a single patient) involved use of oral daily calcium therapy, oral daily vitamin D therapy, and daily injections into the skin of teriparatide, which is often used to treat osteoporosis.  The patient also received pamidronate every 3 months.  She also began core strengthening exercises and was instructed in body mechanics and fall risk reduction techniques.  These therapies led to significant increases in bone formation, without an increase in bone reduction, which is usually found in HCS patients. 

Prognosis

There have been no reports of a decreased lifespan for patients suffering from HCS.  However, so few patients have been reported to have this disorder that there is inadequate literature to definitively state that they do not have a decreased lifespan.  The existing literature tends to focus on younger patients, so it remains unclear what complications adults with HCS can expect.  Certainly, they may continue to suffer pain throughout their lives, and will have an increased risk of complications if they sustain fractures or falls.  Because patients may have spinal abnormalities (including kyphosis and scoliosis), the ability to breathe may be impaired by the misshapen chest cavity.  As therapy for the osteoporosis improves, one may expect that HCS patients may live relatively normal lives.  In time, the genetic cause of the disease will be identified, which should allow for development of better treatments as well. 

Connect with other parents

In the spirit of community and support, Madisons Foundation offers the unique service of connecting parents of children with rare diseases. If you would like to be connected to other parents of children with this disease, please fill out this brief form.

Weblinks

 

Web MD

http://children.webmd.com/Hajdu-Cheney-Syndrome

This website has a brief description of the disorder and links to several other resources.

National Library of Medicine and National Institute of Health

http://www.nlm.nih.gov/mesh/jablonski/syndromes/syndrome331.html

National government website. Type in Hajdu-cheny in the search bar and look under Jablonski in the archives for multiple article listings.

Wikipedia

http://en.wikipedia.org/wiki/Hajdu-Cheney_syndrome

Very brief description with a couple of links to popular sites. Not very scientific

References:

Brennan, AM., and Pauli, RM "Hajdu-Cheney Syndrome: Evolution of Phenotype and Clinical Problems," (2001) Am J Med Genet 100: 292-310.

McKiernan, F.E. "Integrated anti-remodeling and anabolic therapy for the osteoporosis of Hejdu-Cheney syndrome," (2007) Osteoporos Int 18:245-249.

O'Reilly, MAR, and Shaw, DG "Hajdu-Cheney Syndrome" (1994) Ann Rheum Dis 53: 276-279.

Google Search for Hajdu-Cheney

References and Sources