1. Shortening of the involved bones affects specific portions of the growing bone (Figure 3-1); hence the term dwarfism. Most forms of dwarfism are related to gene defects (single or multiple genes; Table 3-1).

1. Short-trunk variety (e.g., Kniest syndrome–spondyloepiphyseal)

2. Short-limb variety (e.g., achondroplasia, diastrophic dysplasia)

1. Achondroplasia is the most common form of disproportionate dwarfism.

2. Autosomal dominant condition; 80% of cases caused by a spontaneous mutation in the fibroblast growth factor receptor 3 (FGFR3)

3. This disproportionate, short-limbed form of dwarfism is caused by abnormal endochondral bone formation that is more affected than appositional growth.

4. Anatomically, achondroplasia is categorized as a physeal dysplasia.

5. Caused by failure in the cartilaginous proliferative zone of the physis. Achondroplasia is a quantitative, not a qualitative, cartilage defect.

6. It may be associated with advanced paternal age.

1. Normal trunk and short limbs (rhizomelic) with hypotonia

2. Frontal bossing, button noses, small nasal bridges, trident hands (inability to approximate extended middle and ring fingers) (Figure 3-2).

3. Thoracolumbar kyphosis (which usually resolves around the age at ambulation)

4. Lumbar stenosis (most likely to cause disability) and excessive lordosis (short pedicles with decreased interpedicular distances)

5. Radial head subluxation

6. Normal intelligence but delayed motor milestones

7. Although sitting height may be normal, standing height is below the third percentile.

8. Radiographic findings

1. Lumbar stenosis: decompression and fusion of the spine for a developing neurologic deficit (usually in children older than age 10)

2. Foramen magnum stenosis: decompression

3. Progressive kyphosis: if fail bracing, anterior and posterior fusion are indicated for residual kyphosis greater than 60 degrees by age 5 years.

4. Genu varum: Tibial osteotomies or hemiepiphysiodesis

5. Limb lengthening through callodiastasis (lengthening through a metaphyseal corticotomy) have been well described, with a high rate of complications.

1. Genetics: The inheritance pattern is autosomal dominant with a defect on chromosome 19 within the cartilage oligometric matrix protein (COMP).

2. Signs and symptoms:

3. Radiographic findings: metaphyseal flaring and delayed epiphyseal ossification

1. Must be differentiated from multiple epiphyseal dysplasia (MED)

2. MED and spondyloepiphyseal dysplasia involve abnormal epiphyseal development in the upper and lower extremities.

3. The distinguishing feature of spondyloepiphyseal dysplasia is the added typical spine involvement.

4. Retinal detachment and respiratory problems are common.

1. Genetic defect is within the gene encoding type II collagen.

1. Characterized by multiple punctate calcifications seen on radiographs during infancy

2. The autosomal dominant form (Conradi-Hünermann) has a wide variation of clinical expression.

3. Autosomal recessive, rhizomelic form is usually fatal during the first year of life.

1. Autosomal dominant; short-trunked, disproportionate dwarfism with joint stiffness/contractures, scoliosis, kyphosis, dumbbell-shaped femora, and hypoplastic pelvis and spine

2. Otitis media and hearing loss are frequent.

1. Defect within type II collagen

1. Osteopenia and dumbbell-shaped bones

1. Early therapy for joint contractures is required. Reconstructive procedures may be required for early hip degenerative arthritis.

1. Heterogeneous group of disorders characterized by metaphyseal changes of tubular bones with normal epiphyses

1. The defect appears to be in the proliferative and hypertrophic zones of the physis.

1. Jansen (rare): most severe form

2. Schmid type

3. McKusick type

1. Short-limbed, disproportionate dwarfism that often is not manifested until between the ages of 5 and 14. It must be differentiated from spondyloepiphyseal dysplasia. A mild form (Ribbing) and a more severe form (Fairbanks) exist.

1. Most common gene mutation is in COMP.

1. MED is characterized by irregular, delayed ossification at multiple epiphyses (Figure 3-3).

2. Short, stunted metacarpals and metatarsals, irregular proximal femora, abnormal ossification (tibial “slant sign” and flattened femoral condyles, patella with double layer), valgus knees (early osteotomy should be considered), waddling gait, and early hip arthritis are common.

3. The proximal femoral involvement can be confused with Perthes disease.

1. Obtain bone survey to differentiate between MED and single epiphyseal dysplasia, as well as to identify all areas of involvement.

2. Treat limb alignment and perform early joint replacement.

1. An epiphyseal osteochondroma

2. Most commonly seen at the knee and ankle

3. Usually affects only one joint

1. Calcifications are seen within the joint.

1. Excision of the prominent overgrowth (if symptomatic) and later osteotomies may be required.

2. Recurrence is a common complication.

1. Autosomal dominant inheritance.

2. Affected children are often “late walkers” (because of associated muscle weakness), with symmetric cortical thickening of long bones.

3. The tibia, femur, and humerus are most often involved (in that order), affecting only the diaphyseal portion of bone.

4. Watch for leg-length inequality.

1. Widened, fusiform diaphyses with increased bone formation and sclerosis

1. Salicylates, nonsteroidal anti-inflammatory drugs (NSAIDs), and steroids for refractory cases

1. In contrast to the aforementioned conditions, these forms of dwarfism are easily differentiated on the basis of the presence of complex sugars in the urine.

2. The accumulation of mucopolysaccharides, as a result of a hydrolase enzyme deficiency, produces a proportionate dwarfism.

1. Morquio syndrome (autosomal recessive)

2. Hurler syndrome (autosomal recessive inheritance)

3. Hunter syndrome (sex-linked recessive inheritance)

4. Sanfilippo syndrome (autosomal recessive inheritance)

1. Autosomal recessive inheritance; severe, short-limbed dwarfism

2. Cleft palate (59% of cases)

3. Severe joint contractures (especially hip and knee)

4. Cauliflower ears (80% of cases), hitchhiker’s thumb

5. Rigid clubfeet

1. Deficiency in sulfate transport protein

1. Spine radiographs reveal cervical kyphosis (often severe, necessitating immediate treatment), thoracolumbar kyphoscoliosis (83% of cases), spina bifida occulta, and atlantoaxial instability.

1. Quadriplegia is a major concern with deformities of the cervical spine.

2. Surgical release of clubfoot deformities

3. Osteotomies for contractures

4. Spinal fusion often required

1. Autosomal dominant inheritance

2. Proportionate dwarfism that affects bones formed by intramembranous ossification (clavicles, cranium, pelvis)

1. Defect in transcription factor for osteocalcin (CBFA1)

1. Hypoplasia or aplasia of the clavicle (no intervention necessary) (Figure 3-4)

2. Delayed closure of skull sutures

3. Frontal bossing

4. Coxa vara

5. Delayed ossification of the pubis

6. Wormian-type bone

1. Consider intertrochanteric valgus osteotomy if neck-shaft angle is less than 100 degrees.

1. Usually characterized by ligamentous laxity, hypotonia, mental retardation, heart disease with atrial septal defect (50% of cases), endocrine disorders (hypothyroidism and diabetes), and premature aging

2. Orthopaedic problems include metatarsus primus varus, pes planus, spinal abnormalities (atlantoaxial instability [Figure 3-5], scoliosis [50% of cases], spondylolisthesis [6% of cases]), hip instability (open reduction with or without osteotomy is usually required), slipped capital femoral epiphysis (SCFE) (hypothyroidism should be sought), patellar dislocation, and symptomatic planovalgus feet.

3. Atlantoaxial instability may be subtle but commonly manifests as a loss or change in motor milestones.

1. Trisomy 21 is the most common chromosomal abnormality; its incidence increases with maternal age.

2. Chromosome 21 is the location of genes that encode for type VI collagen (COL6A1 and COL6A2).

1. Lower extremity radiographs are needed to evaluate for patella dislocations and genu valgum.

2. Anteroposterior and frog-leg pelvic views to evaluate for SCFE

3. Flexion-extension radiographs of the cervical spine to evaluate atlantoaxial instability

1. Screening for cervical spine instability:

2. Children with asymptomatic instability should avoid contact sports, diving, and gymnastics.

3. Children with symptomatic instability often require surgery, but the rate of wound healing problems and infection is high.

1. Affected patients are female and have short stature, lack of sexual development, webbed neck, and cubitus valgus.

2. Idiopathic scoliosis is common. Growth hormone therapy can exacerbate scoliosis.

3. Malignant hyperthermia is common with anesthetic use.

4. Must be differentiated from Noonan syndrome (same appearance except for normal gonadal development, mental retardation, and more severe scoliosis)

1. 45,XO Genotype

1. Genu valgum and shortening of the fourth and fifth metacarpals, which usually necessitate no treatment

1. Monitor for osteoporosis.

1. Floppy, hypotonic infant who grows up to be an intellectually impaired, obese adult with an insatiable appetite

2. Growth retardation

3. Hypoplastic genitalia

1. Partial chromosome 15 deletion (missing portion from father)

1. Hip dysplasia and juvenile-onset scoliosis

1. Characteristic “kinky” hair

2. May be differentiated from occipital horn syndrome (which also affects copper transport) in that the latter is characterized by bony projections from the occiput of the skull

1. Sex-linked recessive disorder of copper transport

1. Skull (wormian bones), long bones (metaphysial spurring), and ribs (anterior flaring and multiple fractures)

1. Progressive impairment and stereotaxic, abnormal hand movements (like those in autism)

2. Manifests in girls at 6 to 18 months of age

3. Loss of developmental milestones that is rapid and then stabilizes

1. Family of deletion mutations of the X-linked gene encoding a protein called methyl-CpG-binding protein 2 (MECP2)

1. Scoliosis with a C-shaped curve that is unresponsive to bracing

1. Spinal instrumentation must include all of the kyphosis and the scoliosis.

2. Spasticity results in joint contractures, which are treated as they are in cerebral palsy.

1. Organomegaly, omphalocele, and a large tongue

2. Orthopaedic manifestations include hemihypertrophy with spastic cerebral palsy.

3. There is a predisposition to Wilms tumor (patient must be screened regularly with kidney ultrasonography).

1. Spasticity is thought to be the result of infantile hypoglycemic episodes secondary to pancreatic islet cell hypertrophy.

1. Growth arrest may be necessary in large limb.

1. Osteopenia

2. Bone pain (Gaucher crisis), and bleeding abnormalities

3. Hepatosplenomegaly (characteristic finding)

4. Types

1. Aberrant autosomal recessive, lysosomal storage disease characterized by accumulation of cerebroside in cells of the reticuloendothelial system. The cause is a deficiency of the enzyme β-glucocerebrosidase.

1. Metaphyseal enlargement (failure of remodeling), femoral head necrosis (may be confused with Perthes disease or MED), “moth-eaten” trabeculae, patchy sclerosis, and Erlenmeyer flask deformity of the distal femora (70% of cases)