Sclerosing bone dysplasias are rare conditions. Estimates of general population frequency range by ethnic group and type of sclerosing bone dysplasia described. Affected individuals can occur within a variety of ethnic backgrounds and cases have been found in countries, including Denmark, Egypt, the United States, Germany, Japan, Italy, Brazil, Spain, Senegal, South Africa, the Netherlands, and Cyprus. A large number of individuals affected by sclerosing bone dysplasias exist in the Afrikaner population of South Africa and the Dutch population of the Netherlands. The carrier rate for the single founder-derived mutation that causes sclerosteosis in the Afrikaner population is approximately one in 100. Van Buchem disease has been recognized predominantly in the Dutch population (±20 cases). Several of the affected families have ancestral origins on the former island of Urk in the Zuider Zee. The prevalence of later onset osteopetrosis or Albers-Schonberg is about one in 18,000 in Denmark.
Sclerosing bone dysplasias are rare genetic disorders characterized by increased skeletal density and excessive bone formation, or overgrowth, due to a defect in the method of replacing old bone with new bone (bone remodeling). Each of the three main categories of sclerosing bone dysplasias exhibit different symptoms, including age of onset, skeletal involvement, and prognosis.
The specific disorders in the group of sclerosing bone dysplasias that exhibits increased bone density without modification of bone shape include: osteopetrosis disorders 9autosomal dominant osteopetrosis types I and II and autosomal recessive osteropetrosis); pycnodysostosis; and osteopathia striata with cranial sclerosis.
The osteopetrosis disorders are conditions that involve increased bone density without modification of bone shape. They include two forms of benign dominant conditions known as autosomal dominant osteopetrosis I (ADOI) and autosomal dominant osteopetrosis II (ADOII), and one form of malignant infantile osteopetrosis (MIOP).
Benign dominant or autosomal dominant osteopetrosis (ADO) typically presents in childhood, adolescence, or young adult life with multiple fractures, mild anomalies in head and face proportions, mild anemia, hearing loss, bone inflammation/infection, or increased bone density found on routine x-ray studies. ADO has two distinct subtypes known as types I and II that are distinguished by the location of sclerosis and presence or absence of increased bone fractures.
Autosomal dominant osteopetrosis type I (ADOI or OPTA1) is characterized by a generalized increase in the hardness, thickness, and density of bone tissue (osteosclerosis), most pronounced in the cranial vault. Patients are often asymptomatic, but some suffer from pain and hearing loss. ADOI appears to be the only type of osteopetrosis not associated with an increased fracture rate.
Autosomal dominant osteopetrosis type II (ADOII or OPTA2) is characterized by an increase in the hardness, thickness, and density of bone tissue (sclerosis) predominantly involving the spine, the pelvis, and the skull base. Fragility of bones and dental abscesses are the leading complications. Other symptoms include arthritis of the hip (hip osteoarthritis), bone infections (osteomyelitis), thoracic or lumbar scoliosis, and cranial nerve involvement responsible for hearing loss, bilateral optic atrophy, and/or facial palsy. Although other forms of osteopetrosis are considerably more severe, it has been suggested that the name benign osteopetrosis, previously used for ADOII, is probably incorrect given the complications of the condition.
Malignant infantile osteopetrosis (MIOP) is characterized by a generalized increase in bone density found at or soon after birth. The sclerosis of the bones causes a
Pycnodysostosis is characterized by an increase in bone density of the skeleton (osteosclerosis), skull deformities, short stature, short limbs, characteristic facial features, and bone fragility. Onset of the symptoms occurs around two or three years of age. Other features of the condition include: separated cranial sutures; large fontanel with delayed closure; obtuse mandibular angle; delayed teeth eruption; enamel hypoplasia; dysplastic acromial ends of the clavicles; frontal bossing; ocular proptosis; and dysplastic nails. Developmental evaluations often indicate normal motor, fine motor-adaptive, language, and personal social abilities.
Osteopathia striata with cranial sclerosis (OSCS) presents with longitudinal striations of dense bone in the long bones and formation of dense bone in the cranial and facial bones in infancy and childhood. The formation of dense bone in the head and face leads to facial disfigurement and to neurological complications, such as deafness due to pressure on cranial nerves. Other features include: a large head (macrocephaly); congenital heart defects, such as aortic stenosis and ventricular septal defects; scoliosis of the back; narrowed visual fields; cleft palate; long fingers; curving of the third to fifth fingers (clinodactyly); clubfoot; facial nerve palsy; and mild mental retardation.
The disorders involving increased bone density with diaphyseal involvement include: progressive diaphyseal dysplasia, or Camurati-Engelmann disease; craniodiaphyseal dysplasia; and endosteal hyperostosis disorders (Van Buchem disease (types I and II) and sclerosteosis).
Progressive diaphyseal dysplasia (PDD), or Camurati-Engelmann disease, is characterized by childhood onset of bone overgrowth (hyperostosis) and increased density (sclerosis) of the diaphyses of the long bones and the skull. Other features may include: a slender build with long limbs; angular profile; prominent bones (asthenic habitus); hearing loss; protruding eyeballs (exophthalmos); optic nerve compression; double vision (diplopia); cavities (dental caries); sclerosis of skull base; lower jaw (mandible) involvement; sclerosis of posterior part of vertebrae (body and arches); scoliosis; progressive diaphyseal widening; thickened cortices; narrowing of medullary canal; erlenmeyer flask defect of the bone; clubfoot (genu varus and valgus deformities); relative muscle weakness, especially in pelvic girdle; atrophic muscle fiber; headaches; delayed puberty; bone marrow hypoplasia; anemia; waddling gait; and leg pain. The most severely affected individuals will have progression of mild skull hyperostosis to severe skull thickening and cranial nerve compression over many years. Presentation of the disease can be very different from one individual to another.
Craniodiaphyseal dysplasia includes a wide variety of symptoms and age of onset from infancy to childhood. Facial and cranial thickening and distortion are particularly striking in this form. The characteristic facial features of craniodiaphyseal dysplasia occur from the overgrowth of bone in the face and skull that results in progressive facial anomalies, a broad nasal bridge, and wide-spaced eyes. Other symptoms of craniodiaphyseal dysplasia, like hearing loss and facial paralysis, are caused by the overgrowth of the skull as it gradually eliminates the perinasal sinuses and the large hole at the base of the skull that allows passage of the spinal cord (foramina of the skull base). Individuals with craniodiaphyseal dysplasia often are affected by mental retardation. Unlike the situation in the craniometaphyseal dysplasias, the long bones do not show metaphyseal flaring, but are shaped like a policeman's nightstick.
Endosteal hyperostosis disorders include Van Buchem disease (types I and II) and sclerosteosis. The two endosteal hyperostosis conditions include many similar features. The two disorders can be distinguished from each other via their different appearance of the bone changes on x ray. Additionally, sclerosteosis includes the presence of asymmetric fusion (cutaneous syndactyly) of the index and middle fingers in many cases, and Van Buchem disease does not.
Van Buchem disease (or hyperostosis corticalis familiaris) is characterized by progressive enlargement of the lower jaw in childhood and symptoms, including hearing loss and facial paralysis, in adulthood caused by the overgrowth of the skull. Van Buchem disease has two distinct subtypes known as types I and II. The subtypes are distinguished by genetic cause, primary location of bone overgrowth, and phosphate levels.
The symptoms of Van Buchem disease type I begin in childhood or puberty and include features resulting from bone overgrowth. Symptoms include: cranial bone overgrowth (hyperostosis) leading to optic nerve compression; hearing loss; headaches; cranial nerve palsy; osteosclerosis; thickened cortex of long bones; and abnormally high blood levels of phosphorous (hyperphosphatasemia).
The signs and symptoms of Van Buchem disease Type II begin in childhood or puberty, and include: enlarged lower jaw bone (mandible); increased skull cap (calvarial) thickness; cranial osteosclerosis; thickened cortices of long bones; and normal alkaline phosphatase levels.
Sclerosteosis is characterized by tall stature, overgrowth of the nasal and facial bones, broad, flat nasal bridge, wide-spaced eyes (hypertelorism), and minor hand malformation, such as finger fusion (syndactyly). Other symptoms may include: small nails (nail dysplasia); square jaw due to overgrowth of the mandible; difficulties in chewing; inability to smell (anosmia); massive bone density (sclerosis) of the long tubular bones, ribs, pelvis, and skull; and multiple cranial nerve involvement resulting in optic atrophy, facial palsy, and trigeminal nerve pain episodes (neuralgia). Facial nerve paralysis may be present as early as birth or develop soon afterwards. Facial palsy and deafness as a result of cranial nerve entrapment often develop in childhood. Increased intracranial pressure may result in sudden death from impaction of the brain stem in the foramen magnum.
The disorders involving increased bone density with metaphyseal involvement include craniometaphyseal dysplasia and frontometaphyseal dysplasia.
Craniometaphyseal dysplasia involves overgrowth bone anomalies that commonly present in infancy. Some of the first indications of a craniometaphyseal dysplasia include breathing difficulties and narrowing nasal passages due to bone overgrowth. The characteristic facial features of craniometaphyseal dysplasia occur from the overgrowth of bone in the face and skull that result in progressive facial anomalies, a broad nasal bridge, and wide-spaced eyes. Other symptoms of craniometaphyseal dysplasia, like hearing loss and facial paralysis, are caused by the overgrowth of the skull as it gradually eliminates the perinasal sinuses and the large hole at the base of the skull that allows passage of the spinal cord (foramina of the skull base). The features of craniometaphyseal dysplasia are more severe than the sclerotic or hyperostotic features, except in the lower jaw where they are less severe than craniodiaphyseal dysplasia.
Frontometaphyseal dysplasia's most striking feature is a characteristic facial appearance that includes a very prominent supraorbital ridge above the eyes resulting from bone overgrowth. In many cases, the prominent ridge may be present at birth, along with a small, pointed chin, wide-spaced eyes (hypertelorism), wide nasal bridge, poor sinus development, clubfoot (coxa valga and genu valgum), and flared metaphyses. Later findings may include: progressive mixed conductive and sensori-neural hearing loss; high palate; teeth issues; mitral valve prolapse; narrow trachea; winged shoulder blade (scapulae); irregular rib contours; "coat hanger" deformity of lower ribs; distended kidneys and ureters (hydronephrosis and hydroureter); scoliosis; cervical vertebral fusion; flared pelvis; elbow contractures; knee and ankle contractures; erlenmeyer-flask appearance of femur and tibia; increased density of long bone diaphyses; finger and wrist contractures; long and wide fingers; partial fusion of the bones of the feet; large feet; overgrowth of hair on the buttocks and thighs; muscle wasting (especially legs and arms); and mental retardation. The skeletal dysplasia and the associated clinical findings show significant variability from affected individual to individual. The syndrome has been suggested to be an allelic variant of the Melnick-Needles osteodysplasty.