Physical Examination for Unusual and Syndromic Conditions

Pooya Hosseinzadeh

Ron El-Hawary

Craig Eberson

Kishore Mulpuri

• Unusual Conditions

Patients present to orthopedic surgeons for management of their musculoskeletal problems. It is imperative for the clinician to realize that these issues may exist in the setting of a genetic/syndromic condition. It is important to realize this for two reasons: first, a known diagnosis may point toward potential areas of concern, facilitating early diagnosis of an associated orthopedic issue; second, by recognizing potential associations, the child presenting with an orthopedic concern (ie, scoliosis) can be examined with the intention to seek other underlying conditions (ie, Marfan syndrome [MFS]). It is often the other associated abnormalities of the specific underlying condition that represent the largest health risk (ie, aortic aneurism).

In other chapters of this book, we focus on how examination of different areas can aid in making a diagnosis of a limb or spine deformity. Many different disorders such as skeletal dysplasia can have effects on the pediatric skeleton in multiple locations. Children with neurofibromatosis may have severe scoliosis and tibial pseudarthrosis in addition to neurofibromas. Children with marfanoid characteristics can have limb deformity, scoliosis, foot deformities, and other conditions. In this chapter, we discuss some of these unusual syndromes and disorders. Instead of looking at a presenting deformity in search of a diagnosis, we consider the whole child with a known diagnosis and look for orthopedic deformities. In addition, we will discuss the evaluation of children with chronic regional pain syndrome.

• Neurofibromatosis

Type 1 neurofibromatosis (NF-1), also known as von Recklinghausen disease, is a condition involving overgrowth of neural tissue leading to multisystem involvement. Orthopedic manifestations and concerns are many.

Diagnosis and Physical Examination Findings

The diagnosis of NF-1 is made by establishing the presence of several physical features (Table 6.1).

Café au lait spots are hyperpigmented lesions that are present in the majority of patients with NF-1 (Figure 6.1).

Cutaneous neurofibromas are mixed cell tumors, consisting predominantly of Schwann cells, and present in late childhood. They are seen on the surface of the skin as well-circumscribed grayish tumors. Plexiform neurofibromas are diffuse tumors that are present under the skin. Lesions that cross the
midline on both sides of the spine often arise from the spinal canal. They have a “bag of worms” appearance and have the potential to undergo transformation to malignant peripheral nerve sheath tumors. This transformation, which often occurs 10 to 20 years after the original tumors present, is usually heralded by sudden onset of pain, enlargement, and new neurological deficits. Axillary Freckling (Figure 6.2) is the second most common feature seen in NF-1.

Table 6.1 Diagnostic Criteria for Neurofibromatosis

More than six café au lait spots (15 mm in adults, 5 mm in children)

Two or more neurofibromas or one plexiform neurofibroma

Axillary or inguinal freckling

Optic glioma

Two or more Lisch nodules (iris hamartomas)

Bone lesions (sphenoid dysplasia, long bone thinning with or without pseudarthrosis)

A first-degree relative with NF-1

Can be remembered with the mnemonic “CAN FOOL” (café au lait, axillary freckling, neurofibromas, first-degree relative, optic glioma, osseous lesion, Lisch nodule)

National Institutes of Health Consensus Development Conference Statement: neurofibromatosis. Bethesda, Md., USA, July 13-15, 1987. Neurofibromatosis. 1988:1(3):172-178.

Other skin findings include macrodactyly, elephantiasis (large soft-tissue masses), and overgrowth of the skin with a velvety, soft, papillary quality, known as verrucous hyperplasia. Children with NF-1 are also known to have an increased risk of developmental delay, stroke, psychiatric disorders, and heart disease.

Orthopedic Manifestations

Roughly half of patients with NF-1 will have a spinal deformity. While many present with curves which resemble idiopathic scoliosis, these curves may undergo transformation to the dystrophic curves characteristic of NF-1 (Figure 6.3).

Nondystrophic curves progress in a manner similar to adolescent idiopathic scoliosis, but dystrophic curves can progress rapidly and relentlessly. The later curves are usually short, sharply angular, and may have significant kyphosis (Table 6.2).

Bony abnormalities include vertebral wedging, narrowing of the pedicles, and dural ectasia, which erode into the vertebral body. This leads to vertebral scalloping and thinning of the pedicles, factors that may make fixation during surgery difficult. Magnetic resonance imaging should be considered for patients with NF-1 presenting with scoliosis to screen for intraspinal tumors.

Other orthopedic manifestations include congenital pseudarthrosis of the tibia, as well as other bony dysplasias. While the tibia is the most commonly affected, other bones can be involved as well (Figure 6.4).

FIGURE 6.1 Multiple café au lait spots in a patient with neurofibromatosis.

FIGURE 6.2 Axillary freckling in a patient with neurofibromatosis.

The term “congenital pseudarthrosis of the tibia” is confusing to many and would imply that children are born with a nonunion of their tibia. The confusion rests in the fact that most children with this condition are born without an established
fracture with just anterolateral bowing of the tibia (and often the fibula) and with time, the tibia will fracture and not heal. Adding further confusion is the reality that not all children with NF-1 and anterolateral bowing will ever fracture. Treatment is complex and fraught with difficulties.

FIGURE 6.3 A, This 10-year-old boy with NF-1 has a 60° scoliosis. B, A close-up view of the curve demonstrates dystrophic changes with vertebral scalloping (dashed red line) and rib penciling (red arrow). C, Lateral X-ray. D, A close-up of the lateral X-ray demonstrates further vertebral scalloping which is likely due to dural ectasia. E, MRI demonstrates a large neurofibroma is the concavity of the curve. F and G, This child underwent anterior and posterior spine fusion.

Table 6.2 Dystrophic Spinal Changes in NF-1

Dural ectasia leading to vertebral scalloping

Foraminal enlargement from dumbbell neurofibromas

Rib penciling

Short, sharply angular curves

Dysplastic pedicles

Kyphoscoliosis

Limb overgrowth is an additional finding on examination. Limb hyperplasia and overgrowth are common. Subperiosteal bone growth has also been noted and may be responsible for irregular bone elongation.

Differential Diagnosis

The diagnosis of NF-1 is usually easy to make based upon the presence of nonorthopedic lesions such as café au lait spots and axillary freckling. When faced with a child with hemihypertrophy, NF-1 should stay on the list of possible causes until definitive diagnosis is made. Other causes include Proteus syndrome, Klippel-Trenaunay-Weber (KTW) syndrome, and Beckwith-Wiedemann syndrome.

FIGURE 6.4 This girl with NF-1 was born with anterolateral bow of the tibia that one month later developed fracture and worsening deformity.

• Hemihypertrophy

Hemihypertrophy is a rare condition where one side of the body is enlarged compared to the other side of the body. Based on the degree of enlargement, patients may present during infancy or not until they are school-aged.

Pathophysiology

The mechanism of enlargement in patients with hemihypertrophy is unknown and may affect an entire side of the body or often it may affect just one of the lower extremities. In classic hemihypertrophy, the femur and the tibia on the affected side are longer than the femur and tibia on the normal side and the affected foot is usually larger (Figure 6.5).

In evaluated children with apparent hemihypertrophy, one should recognize that it may not be enlargement of one limb but actually atrophy of the other limb secondary to other causes.

Differential Diagnosis and Physical Examination Findings

In mild cases of hemihypertrophy, it may be difficult to differentiate one from having a hypoplastic limb on the other side. Recent work has provided normative data for the developing child’s upper limb length, girth, and circumference to aid the practitioner. In other cases, the upper and lower limbs are markedly enlarged and the diagnosis is obvious (Figure 6.6).

The practitioner should look for signs and symptoms of associated conditions such as NF-1 (see above), Proteus syndrome (asymmetric enlargement) (Figure 6.7), Beckwith-Wiedemann (enlarged tongue), and KTW syndrome (port-wine stains and vascular abnormalities under the skin) (Figures 6.8 and 6.9).

Orthopedic Manifestations

An enlarged limb can lead to limb length discrepancy that may require treatment. As outlined in the chapter on limb length discrepancy, treatment may include a shoe lift for minor discrepancies in symptomatic patients, growth arrest timed to effectuate correction, or limb lengthening of the short limb. Parents and patients often relate difficulty with shoe wear for the differences in foot size and can be bothered by cosmetic differences in limb girth. Unfortunately, little corrective treatment can be done for these issues and accommodative measures with different shoe sizes are usually all that is available.

Differential Diagnosis

The list of conditions that can cause atrophy can include hemiplegia or other neurologic disorders as well as congenital limb deficiency syndromes. Toddlers with mild congenital short femur can be misdiagnosed with hemihypertrophy of the normal limb. As the child ages, it becomes clear that only the femur is affected and other signs such as genu valgum and anterior knee laxity (absent cruciate ligament) confirm that the short limb is the abnormal limb. True limb enlargement (hemihypertrophy) is discussed above and includes Proteus syndrome, NF-1, KTW, and Beckwith-Wiedemann syndrome. Advanced imaging studies such as angiography and magnetic resonance imaging are often sufficient for a diagnosis of the associated conditions, but biopsy of suspected neurofibroma may be required to diagnose NF-1. In KTW, “benign” vascular tumors and arteriovenous malformations can lead to high-output cardiac failure if sufficiently large. Even when small, these lesions can be infiltrative, disfiguring, and painful. In children with apparent idiopathic hemihypertrophy, it is critical to consider that this may actually represent Beckwith-Wiedemann syndrome with a risk for development of intraabdominal tumors. Routine abdominal ultrasounds should be obtained every 3 to 4 months in patients with hemihypertrophy until the age of seven.

FIGURE 6.5 This 12-year-old boy with hemihypertrophy has a 4.2 cm discrepancy, 2.4 cm in the femur, and 1.8 cm in the tibia.

FIGURE 6.6 This 4-month-old baby has enlargement of his upper and lower extremity consistent with a diagnosis of hemihypertrophy. Abdominal ultrasound examinations must be obtained every 3 to 6 months to rule out tumor such as hepatoblastoma or Wilms tumor that are seen in Beckwith-Wiedemann syndrome.

FIGURE 6.7 This Honduran boy with Proteus syndrome has hypertrophy of the left thigh and foot with hypertrophy of the right calf.

FIGURE 6.8 This boy with Klippel-Trenaunay-Weber syndrome has port-wine stain of the right upper extremity. His arm is longer and his hand is larger.

FIGURE 6.9 This boy with severe Klippel-Trenaunay-Weber syndrome has vascular malformations on the right side of his body from his trunk, to his thigh, and down to his foot.

• Marfan Syndrome

MFS is a disorder of connective tissue that results in many different orthopedic deformities and can have varying effects on the patient’s appearance and function. The systemic scoring system for the diagnosis of MFS is a helpful guide to the features of MFS (Table 6.3).

It is important to diagnose the condition as some may have life-threatening cardiovascular pathology. The phenotype may range from classic MFS with ocular and cardiovascular pathology to patients who have “marfanoid characteristics” with a few features such as increased height, arachnodactyly, and pectus excavatum or carinatum.

Diagnosis and Physical Examination Findings

Cardiovascular findings include aortic root dilatation and dissection, mitral valve prolapse, pulmonary artery enlargement, and left ventricular disease. Ocular manifestations include lens dislocation, glaucoma, cataracts, and retinal detachment. Patients often have high arched palates. Frequently, the orthopedic manifestations of the disease are the first symptoms that warrant medical attention. In these cases where the patient presents with a constellation of orthopedic features of MFS, the provider is well justified in referral to genetics and cardiology.

Orthopedic Manifestations

The physical examination findings of MFS are paramount in raising suspicion of the disease and prompting further workup. Chest wall deformities are common such as pectus excavatum or carinatum (Figure 6.10).

Table 6.3 Systemic Scoring System for the Diagnosis of Marfan Syndrome

FEATURE (POINTS)		MAXIMUM POSSIBLE SCORE
Chest deformity		2
	Pectus carinatum deformity (2)
	Pectus excavatum (1)
	Chest asymmetry (1)
Dural ectasia (2)		2
Facial features^a (1)		1
Foot deformity		2
	Hindfoot deformity (2)
	Pes planus (1)
Mitral valve prolapse, all types (1)		1
Myopia >3 diopters (1)		1
Pneumothorax (2)		2
Protrusio acetabuli (2)^b		2
Reduced elbow extension (1)		1
Reduced US/LS ratio^b, increased arm/height, and no severe scoliosis (1)		1
Skin striae (1)		1
Spine deformity		1
	Scoliosis (1)
	Thoracolumbar kyphosis (1)
Wrist and thumb deformities		3
	Wrist sign (1)
	^aThumb sign (1)
	Wrist and thumb signs (3)
	Maximum total score	20
^aPresence of three of the following features: dolichocephaly enophthalmos, downslanting palpebral fissures, malar hypoplasia, retrognathia. ^bLS, lower segment; US, upper segment. US length is the total arm span from each finger. LS is measured from the top of the symphysis pubis to the floor.
Adapted with permission from Loeys B, Dietz H, Braverman A, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010;47(7):476-485.

Arachnodactyly is a prominent feature of MFS. The wrist (Walter Murdoch sign) and thumb (Steinberg sign) features should be sought (Figure 6.11).

Musculoskeletal findings include asymmetric genu valgum (

Video 6.1), spinal deformity, pes planus (Figure 6.12), and protrusio acetabuli.

Protrusio acetabuli refers to an abnormally deep hip socket, which leads to the femoral head migrating medially and protruding into the pelvic cavity (Figure 6.13).

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