Skeletal Dysplasias

CHAPTER 68

Skeletal Dysplasias

Introduction/Etiology/Epidemiology

• Skeletal dysplasias (osteochondrodysplasias) are characterized by abnormal cartilage and bone growth, resulting in abnormal shape and disproportionate size of limbs, trunk, or skull.

• There are more than 400 different clinically identifiable skeletal dysplasias. They are classified based on their clinical, radiographic, and/or molecular phenotypes.

— The 4 most common are achondroplasia (dwarfism) (see Chapter 72, Achondroplasia), achondrogenesis, osteogenesis imperfecta (OI), and thanatophoric dysplasia.

• Incidence is approximately 1 in 4,000 live births.

• Etiology generally falls into 1 of 3 categories.

— Defects in developmental genes

— Abnormalities of matrix structural proteins

— Defects in enzymes that process protein

• Modes of inheritance include autosomal dominant, autosomal recessive, X-linked dominant, and X-linked recessive.

• Males and females are equally affected except for X-linked conditions.

• Many skeletal dysplasias involve multiple, seemingly unrelated defects all arising from a single gene abnormality.

— For example, chondroectodermal dysplasia, which is recessively inherited, is characterized by 6 fingers, fine hair, cardiac abnormalities, immune deficiencies, and angular deformity of the lower limbs, with extreme genu valgum developing over time.

• Some skeletal dysplasias are also associated with abnormalities in other systems (eg, cardiac, neurologic, metabolic, hematologic).

Signs and Symptoms

• Signs of a skeletal dysplasia are often identified at birth or when the child begins to walk or demonstrates developmental abnormalities.

• Signs and symptoms will vary depending on the specific syndrome; however, there are many common features of skeletal dysplasias (Box 68-1).

• Skeletal dysplasias are classified in part based on the areas of the long bones that manifest radiographic abnormalities (Figure 68-1).

Box 68-1. Features Common to Most Skeletal Dysplasias

• Short stature (below third percentile)

• Disproportionate limb and body size (relatively short trunk or limbs)

• Abnormal facial characteristics

• Deformities of the head, neck, hands, and feet (eg, polydactyly, craniosynostosis, disproportionately large head, clubfoot, radial ray defects)

• Hip dysplasia

• Angular deformity of the limbs

• Spinal abnormalities, such as kyphosis and atlantoaxial instability

• Gait disturbances

• Developmental delay

• Family members with atypical appearance or similar features to affected child

Figure 68-1. Illustration demonstrating the different portions of the appendicular skeleton that manifest radiographic abnormalities that aid in the clinical classification of the skeletal dysplasias.

Differential Diagnosis

• Chromosomal disorders, such as trisomy 18 or 21

• Endocrine disorders, such as growth hormone deficiency, Shwachman syndrome, and hyperparathyroidism

• Rickets

• Syndromes associated with diffuse bony lesions, such as Ollier or Maffucci syndrome (multiple enchondromatosis) and McCune-Albright syndrome (fibrous dysplasia with endocrine abnormality)

• Inborn errors of metabolism, such as cystinosis

• Intrauterine growth retardation, constitutional growth delay, or growth failure

• Severe malnutrition

• Child abuse and neglect

• Failure to thrive

• Apert syndrome

• Cornelia de Lange syndrome

• Crouzon syndrome

• DiGeorge syndrome

• Fanconi syndrome

• Cystic fibrosis

• Cytomegalovirus infection

• Perthes disease (bilateral cases)

Diagnostic Considerations

• Most skeletal dysplasias are diagnosed based on the history, physical examination (Figure 68-2), and radiographic findings (Box 68-2).

— When a skeletal dysplasia is suspected, a skeletal survey is performed, including the following radiographic views:

■Anteroposterior (AP) and lateral skull

Figure 68-2. Skeletal dysplasia. Note short stature, disproportionate limb and body size, and angular limb deformities.

From Beals RK, Horton W. Skeletal dysplasias: an approach to diagnosis. J Am Acad Orthop Surg. 1995;3(3):174–181. Reproduced with permission.

Box 68-2. Examples of Radiographic Findings in Skeletal Dysplasia

• Delayed ossification

• Dumbbell-shaped long bones (Kniest dysplasia and metatrophic dysplasia)

• Bowing of limbs (camptomelic dysplasia, osteogenesis imperfecta [OI] syndromes, thanatophoric dysplasia)

• Metaphyseal flaring and cupping at the ends of the rib and long bones (achondroplasia, metaphyseal dysplasias, asphyxiating thoracic dysplasia, chondroectodermal dysplasia)

• Long bone fractures (OI syndromes, hypophosphatasia, osteopetrosis, achondrogenesis type I)

• Irregular formation of epiphyseal ossification centers (spondyloepiphyseal dysplasia [SED] congenita, multiple epiphyseal dysplasia, other SED)

• Cone-shaped epiphyses (acrodysostosis, cleidocranial dysplasia, trichorhinophalangeal dysplasia)

• Stippling of the epiphyses (multiple epiphyseal dysplasia, SED, chondrodysplasia punctata, cerebrohepatorenal syndromes, lysosomal storage diseases, Smith-Lemli-Opitz syndrome)

• Rib shortening (short-rib polydactyly syndromes, asphyxiating thoracic dysplasia, chondroectodermal dysplasia, metaphyseal dysplasia, metatrophic dysplasia)

• Uncalcified vertebral bodies (achondrogenesis types I and II)

• Small sacrosciatic notch (achondroplasia, Ellis-van Creveld syndrome, metatrophic dysplasia, thanatophoric dysplasia, Jeune syndrome)

• Kyphosis/scoliosis (achondroplasia)

• Scapular hypoplasia (camptomelic dysplasia, Antley-Bixler syndrome)

■AP and lateral thoracolumbar spine

■AP pelvis

■AP of one upper limb, including the hand

■AP of one lower limb

— Family history is a key component in establishing the diagnosis and mode of inheritance.

• Prenatal ultrasonography may diagnose many types of skeletal dysplasias.

• Most skeletal dysplasias now have confirmatory genetic testing.

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