Osteochondrodysplasia
Osteochondrodysplasia | |
---|---|
Other names | Skeletal dysplasia |
Specialty | Orthopedic |
An osteochondrodysplasia,[note 1] or skeletal dysplasia, is a disorder of the development of bone and cartilage.[1] Osteochondrodysplasias are rare diseases. About 1 in 5,000 babies are born with some type of skeletal dysplasia.[2] Nonetheless, if taken collectively, genetic skeletal dysplasias or osteochondrodysplasias comprise a recognizable group of genetically determined disorders with generalized skeletal affection. These disorders lead to disproportionate short stature and bone abnormalities, particularly in the arms, legs, and spine.[3] Skeletal dysplasia can result in marked functional limitation and even mortality.
Osteochondrodysplasias or skeletal dysplasia subtypes can overlap in clinical aspects, therefore plain radiography is absolutely necessary to establish an accurate diagnosis.[4] Magnetic resonance imaging can provide further diagnostic insights and guide treatment strategies especially in cases of spinal involvement. As some disorders that cause skeletal dysplasia have treatments available, early diagnosis is particularly important, but may be challenging due to overlapping features and symptoms[5] that may also be common in unaffected children.
Types
Achondroplasia
Achondroplasia is a type of
Pseudoachondroplasia
Pseudoachondroplasia is an osteochondrodysplasia made distinctive by disproportionate short stature, hip and knee deformities, brachydactyly (short fingers) and ligamentous laxity. It affects at least 1 in 20,000 individuals. Pseudoachondroplasia is inherited in an autosomal dominant manner and is caused solely by mutations in the cartilage oligomeric matrix protein COMP gene.[7] It’s distinguished by a moderate to severe form of disproportionate short-limb short stature. The limb shortening is fundamentally confined to the proximal limb segments i.e., Femurs and humeri. A known presenting feature is a waddling gait, noticed at the onset of walking. A prompt diagnosis of a skeletal dysplasia in general and Pseudoachondroplasia in specific is still based upon a comprehensive clinical and radiographic correlation.[4] A detailed radiographic examination of the axial and appendicular skeleton is invaluable for the differential diagnosis of Pseudoachondroplasia. Coxa vara (reduced neck shaft angle), broad femoral necks, short femurs and humeri, and bullet-shaped vertebrae are noticeable radiographic features. Additionally, the presence of metaphyseal broadening, cupping and dense line of ossification about the knee can simulate rachitic changes. These radiographic features are collectively known as rachitic-like changes. The presence of epiphyseal changes serves as an important differentiating feature from achondroplasia.[4]
Osteogenesis imperfecta
COL1A1/2-related osteogenesis imperfecta is inherited in an autosomal dominant manner. The proportion of cases caused by a De novo COL1A1 or COL1A2 mutations are the cause of osteogenesis imperfecta in the vast majority of perinatally lethal osteogenesis imperfecta, and progressively deforming osteogenesis imperfecta. In classic non-deforming osteogenesis imperfecta with blue sclerae or common variable osteogenesis imperfecta with normal sclerae, nearly 60% of cases are de novo. COL1A1/2-related osteogenesis imperfecta is identified by repeated fractures with trivial trauma, defective dentinogenesis imperfecta (DI), and hearing loss. The clinical features of COL1A1/2-related osteogenesis imperfecta can be highly variable ranging from severe and lethal perinatal fractures to individuals with minimal tendency to repeated fractures and skeletal deformities and with a normal stature and life span. In between the clinical spectrum may include individuals with various degrees of disabling skeletal deformities and short stature.[8] The radiographic findings of osteogenesis imperfecta include; long bone deformations such as bowing of the tibias and femurs, pencil-like deformity and tapering of bones, cortical thinning and rarefaction, pathologic fractures at various degrees of healing, bone shortening and vertebral wedging.[4] Accordingly, COL1A1/2-related osteogenesis imperfecta has been classified into four sub-types (I, II, III, and IV) built upon the diversity of the radioclinical features.[9]
Mucopolysaccharidosis
Cleidocranial dysostosis
Cleidocranial dysostosis is a general skeletal condition named for the
- Partly or completely missing collarbones.
- A soft spot or larger soft area in the top of the head where the fontanelle failed to close.
- Bones and joints are underdeveloped.
- The permanent teeth include supernumerary teeth.
- Permanent teeth not erupting
- Bossing (bulging) of the forehead.
- Hypertelorism
Fibrous dysplasia
Fibrous dysplasia causes bone thinning[13] and growths or lesions in one or more bones of the human body.
These lesions are
Langer–Giedion syndrome
Langer–Giedion syndrome is a very rare
Maffucci syndrome
Maffucci syndrome is a sporadic disease characterized by the presence of multiple enchondromas associated with multiple simple or cavernous soft tissue hemangiomas. Also lymphangiomas may be apparent.[16]
Patients are normal at birth and the syndrome manifests during childhood and puberty. The enchondromas affect the extremities and their distribution is asymmetrical.[17]
Osteosclerosis
Osteosclerosis, an elevation in bone density,[18] is normally detected on an X-ray as an area of whiteness and is where the bone density has significantly increased.
Other
- Deformity type Erlenmeyer flask gives a distal Gaucher disease.[19]
- Kashin–Beck disease
- Melnick–Needles syndrome
- Ovine chondrodysplasia
- Familial osteodysplasia, Anderson type
Diagnosis
The diagnosis is mainly based upon delineating the specific clinical and radiographic pattern of skeletal involvement. However, the different types of skeletal dysplasia can overlap considerably in their clinical presentation. Molecular or genetic analysis may be required to resolve diagnostic difficulties.
Differential diagnosis
Juvenile idiopathic arthritis may closely resemble the clinical presentation of some osteochondrodysplasias or genetic skeletal dysplsias. In that, both conditions can present with swollen, stiff and deformed joints.[20][21]
Type II collagen disorders are caused by variants in the COL2A1 gene. Type II collagen disorders can result in mild disease or severe which can cause death within weeks of birth. Infants with the severe form of the disease would be born with clear indications of the disease, such as disproportionate short stature, skeletal dysplasia, distinctive eye abnormalities, cleft palate, and others. However, infants with mild disease may only experience arthritis at birth, but may progress to more severe disease later in life. Early diagnosis can be challenging. Furthermore, type II collagenopathies have significant phenotypic overlap with conditions such as MPS. Guidelines are available to ensure healthcare professional are aware of the conditions and the symptoms of disease to support efficient diagnosis.[22]
Treatment
Emerging therapies for genetic skeletal dysplasias include enzyme replacement therapy,
Even with treatments such as enzyme replacement therapy and stem cell transplantation, people with skeletal dysplasia often require orthopedic surgery and other disease management interventions. There is a lack of information available to support these patients as most physicians may only see one or two skeletal dysplasia patients in their lifetime. Guidelines are available to support best practices for managing several areas of skeletal dysplasia, such as the craniofacial aspects of skeletal dysplasia,[28] spinal disorders,[5] diagnosis and management of type II collagen disorders,[22] pregnancy of people with skeletal dysplasia,[29] peri-operative management,[30] and foramen magnum stenosis in achondroplasia.[31] Written and video resources for patients with skeletal dysplasia and caregivers are also available.
Management
Timely management of skeletal dysplasia is important to combat functional deterioration.[4] Due to rarity of the individual disorders that cause skeletal dysplasia, management can be challenging if a patient does not have access to a facility that has physicians who specialize in skeletal dysplasia. Guidelines have been developed for the management different aspects of skeletal dysplasia,[32] including best practices for managing craniofacial[28] and spinal manifestations,[5] diagnosis and management of type II collagen disorders,[22] pregnancy of people with skeletal dysplasia,[29] peri-operative management,[30] and foramen magnum stenosis in achondroplasia.[31] Written and video resources to support patients with skeletal dysplasia and caregivers are also available.
Footnotes
Notes
- Ancient Greekὀστέο(ν) (ostéo(n)) 'bone', χόνδρο(ς) (khóndro(s)) 'cartiledge', δυσ (dus) 'badly', and -πλασίᾱ (-plasíā) 'formed'.
References
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- ^ PMID 32580780. Retrieved 2023-12-13.
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- PMID 20301660. Retrieved 16 April 2018.
- PMID 20301472. Retrieved 16 April 2018.
- ^ "Osteogenesis Imperfecta - Children's Health Issues". Merck Manuals Consumer Version. Retrieved 2022-11-18.
- ^ a b "Mucopolysaccharidoses". NORD (National Organization for Rare Disorders). Retrieved 2022-11-18.
- ^ "Mucopolysaccharidoses - Children's Health Issues". Merck Manuals Consumer Version. Retrieved 2022-11-18.
- ^ "Cleidocranial Dysplasia". NORD (National Organization for Rare Disorders). Retrieved 2022-11-18.
- ^ "fibrous dysplasia of bone" at Dorland's Medical Dictionary
- ^ "Fibrous Dysplasia". NORD (National Organization for Rare Disorders). Retrieved 2022-11-18.
- PMID 16528117– via PubMed.
- ^ "Maffucci Syndrome". NORD (National Organization for Rare Disorders). Retrieved 2022-11-18.
- ^ "Maffucci syndrome: MedlinePlus Genetics". medlineplus.gov. Retrieved 2022-11-18.
- ^ "Medcyclopaedia - Osteosclerosis". Retrieved 2007-12-23.
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- ^ "Publications". Skeletal Displasia Management Consortium. 27 February 2023. Retrieved 14 December 2023.