Hajdu-Cheney syndrome
Overview
Hajdu-Cheney syndrome is an extremely rare genetic disorder of the connective tissue characterized by severe and excessive bone resorption leading to osteoporosis and a wide range of other potential symptoms. Approximately 50 cases have been reported worldwide.
Symptoms
- Small stature
- Osseous compression
- Wormian cranial bones
- Ossification failure of sutures
- Thickened skull vault
- Absence of frontal sinus
- Elongated sella turcica
- Progressive basilar impression
- Foramen magnum impaction
- Hydrocephalus
- Bathrocephaly
- Thick hair
- Straight hair
- Prominent eyebrows
- Down slanting space between eyelids
- Low set ears
- Prominent ear lobes
- Broad nose
- Anteverted nostrils
- Long philtrum
- Small mandible
- Resorption of alveolar process
- Early loss of teeth
- Biconcave vertebrae
- Tall lumbar vertebral bodies
- Narrow vertebral disk spaces
- Osteopenia
- Kyphoscoliosis
- Short neck
- Short distal digits
- Short nails
- Acrosteolysyis of distal digits
- Pseudoclubbing of distal digits
- Crowded carpal bones
- Joint laxity
- Long fibula
- Bowed fibula
- Osteopenia
- Fractures
- Osteolysis of radius
- Hyperflexible interphalangeal joints
- Highly arched palate
- Uvular abnormalities
- Cleft palate
- Malocclusion
- Hearing loss
- Hoarse voice
- Cataract
- Nystagmus
- Protruding eyeballs
- Widely spaced eyes
- Epicanthal folds
- Optic atrophy
- Umbilical hernia
- Inguinal hernia
- Osteoporosis
Causes
The cause of primary osteoporosis is unknown; however, a mild but prolonged negative calcium balance, resulting from an inadequate dietary intake of calcium, may be an important contributing factor — as may declining gonadal or adrenal function, faulty protein metabolism due to estrogen deficiency, and sedentary lifestyle. Causes of secondary osteoporosis are many: prolonged therapy with steroids or heparin, total immobilization or disuse of a bone (as with hemiplegia, for example), alcoholism, malnutrition, malabsorption, scurvy, lactose intolerance, osteogenesis imperfecta, Sudeck’s atrophy (localized to hands and feet, with recurring attacks), and endocrine disorders (hypopituitarism, acromegaly, thyrotoxicosis, long-standing diabetes mellitus, hyperthyroidism). The incidence of osteoporosis is high, with an estimated 10 million U.S. residents suffering from osteoporosis and another 18 million suffering from low bone mass, or osteopenia. Incidence is higher in women than in men, with women older than age 50 accounting for 20% of cases. Another 30% of women have osteopenia, which can deteriorate into osteoporosis.
Diagnosis
Differential diagnosis must exclude other causes of rarefying bone disease, especially those affecting the spine, such as metastatic cancer and advanced multiple myeloma. The differential diagnosis should also exclude osteomalacia, osteogenesis imperfecta tarda, skeletal hyperparathyroidism, and hyperthyroidism. Initial evaluation attempts to identify the specific cause of osteoporosis through the patient history.
Bone mineral density testing is performed in dual-energy X-ray absorptiometry (DEXA) and measures the mineralization of bones. It’s the gold standard for evaluating osteoporosis.
A spine computed tomography scan shows demineralization. Quantitative computed tomography can evaluate bone density but is less available and more expensive than DEXA.
X-rays show fracture or vertebral collapse in severe cases.
Urine calcium can provide evidence of bone turnover but is limited in value. Newer tests include urinary N-telopeptide to help diagnose osteoporosis.
Treatment
Since about 2002, some patients with this disorder have been offered drug therapy with bisphosphonates (a class of osteoporosis drugs) to treat problems with bone resorption associated with the bone breakdown and skeletal malformations that characterize this disorder.