What are the other Names for this Condition? (Also known as/Synonyms)

• Acroosteolysis Dominant Type (AOD)
• Cranioskeletal Dysplasia with Acro-Osteolysis
• Serpentine Fibula-Polycystic Kidneys Syndrome (SFPKS)

What is Hajdu-Cheney Syndrome? (Definition/Background Information)

• Hajdu-Cheney Syndrome (HJCYS), also known as Acroosteolysis Dominant Type (AOD), is a condition characterized by bone abnormalities throughout the body
• The signs and symptoms of this disorder vary greatly but may include  osteoporosis (loss of bone mass), compression fractures, skull deformities, and curvature of the spine (scoliosis)
• The abnormalities associated with this condition may lead to short stature. Loss of bone (osteolysis) in the hands and feet is a characteristic feature of this condition
• Other features of HJCYS may include distinctive facial features, loose joints, dental problems, excess body hair, recurrent infections, heart defects, and kidney abnormalities
• HJCYS is caused by mutations in the NOTCH2 gene. The mutation can be inherited from a parent, or it can be the result of a new mutation in the affected individual
• Though osteoporosis and respiratory dysfunction can cause problems for individuals with this condition, life expectancy is typically normal

(Source: Hajdu-Cheney Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Hajdu-Cheney Syndrome? (Age and Sex Distribution)

• Hajdu-Cheney Syndrome is a rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Hajdu-Cheney Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Hajdu-Cheney Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for HJCYS

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Hajdu-Cheney Syndrome? (Etiology)

• Hajdu-Cheney Syndrome is caused by mutations in the NOTCH2 gene
• It is inherited in an autosomal dominant manner. However, most cases result from a new mutation and occur in people with no family history of the condition

(Source: Hajdu-Cheney Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Hajdu-Cheney Syndrome?

The signs and symptoms of Hajdu-Cheney Syndrome may include:

• Abnormality of the cardiac septa
• Basilar impression
• Cervical instability
• Conductive hearing impairment
• Crowded carpal bones
• Cryptorchidism
• Dental malocclusion
• Dislocated radial head
• Epicanthus
• Foot acroosteolysis
• Genu valgum
• High palate
• Hirsutism
• Joint laxity
• Kyphoscoliosis
• Large earlobe
• Long eyelashes
• Osteolytic defects of the phalanges of the hand
• Osteolytic defects of the phalanges of the toes
• Pathologic fracture
• Premature loss of teeth
• Renal cyst
• Tall lumbar vertebral bodies
• Vertebral compression fractures

Very frequently present symptoms in 80-99% of the cases:

• Brachydactyly
• Decreased skull ossification
• Downslanted palpebral fissures
• Hypertelorism
• Long philtrum
• Micrognathia
• Osteolysis
• Osteopenia
• Osteoporosis
• Partial absence of toe
• Periodontitis
• Short distal phalanx of finger
• Short toe
• Skeletal dysplasia
• Thick eyebrow

Frequently present symptoms in 30-79% of the cases:

Occasionally present symptoms in 5-29% of the cases:

• Abnormality of the voice
• Aortic valve stenosis
• Bowing of the long bones
• Cataract
• Coarse hair
• Delayed puberty
• Dry skin
• Failure to thrive
• Headache
• Hepatomegaly
• Hydrocephalus
• Hypoplasia of the zygomatic bone
• Hypospadias
• Inguinal hernia
• Intestinal malrotation
• Iris coloboma
• Kyphosis
• Low anterior hairline
• Low-set ears
• Mitral stenosis
• Multiple renal cysts
• Myopia
• Patellar dislocation
• Patent ductus arteriosus
• Pectus carinatum
• Peripheral neuropathy
• Recurrent respiratory infections
• Rough bone trabeculation
• Skin ulcer
• Splenomegaly
• Synophrys
• Syringomyelia
• Thickened skin
• Umbilical hernia
• Ventricular septal defect
• Wide nasal bridge

(Source: Hajdu-Cheney Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Hajdu-Cheney Syndrome Diagnosed?

Hajdu-Cheney Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Hajdu-Cheney Syndrome?

The complications of Hajdu-Cheney Syndrome may include:

• Increased susceptibility to fractures
• Respiratory complications
• Decreased quality of life

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Hajdu-Cheney Syndrome Treated?

There is no cure for Hajdu-Cheney Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops.

How can Hajdu-Cheney Syndrome be Prevented?

Currently, Hajdu-Cheney Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Hajdu-Cheney Syndrome? (Outcomes/Resolutions) 

• The prognosis of Hajdu-Cheney Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Hajdu-Cheney Syndrome:

Hajdu-Cheney Syndrome is also known by the following names:

• Acroosteolysis with Osteoporosis and Changes in Skull and Mandible
• Arthro-Dento-Osteo Dysplasia
• Arthrodentoosteodysplasia
• Cheney Syndrome
• Familial Osteodysplasia
• Hereditary Osteodysplasia with Acro-Osteolysis

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/