Leg Size Asymmetry in a Toddler

HISTORY
Two-year-old girl with asymmetry of leg size at birth; left leg is larger than right. The size discrepancy has remained relatively constant since birth, with no sudden change in overgrowth of the affected limb.

Child born to a 34-year-old, gravida 2, para 1 mother at term via cesarean delivery because of deceleration of fetal heart rate during labor. Pregnancy complicated by maternal hyperthyroidism that required treatment with propylthiouracil. Parents healthy and nonconsanguineous, with no family history of any tumors or growth abnormalities.

PHYSICAL EXAMINATION
With the child lying down, height measured 85.8 cm from the left foot to the head and 85.5 cm from the right foot to the head. Foot length 14 cm on the left, 12 cm on the right. Midthigh circumference 30 cm on the left, 28 cm on the right. Calf circumference 23 cm on the left, 21 cm on the right. Slight facial asymmetry noted but no macroglossia, associated dysmorphic features, vascular lesions, or birthmarks. Otherwise normal examination findings.

WHAT’S YOUR DIAGNOSIS?

(Answer on next page)

ANSWER:  ISOLATED HEMIHYPERPLASIA

Hemihyperplasia, also known as hemihypertrophy, is an asymmetric overgrowth of 1 or more body parts; it can occur in isolation or in association with a syndrome.¹ Patients may also have associated asymmetry in the size of internal organs.² Isolated hemihyperplasia (IHH) is the result of abnormal cell proliferation. Because this underlying pathology is an abnormal proliferation of cells rather than an increase in individual cell size, hemihyperplasia is replacing the term “hemihypertrophy.”² Hemihyperplasia has been classified as complex and simple. Complex hemihyperplasia involves half of the body, including at least 1 arm and 1 leg, whereas simple hemihyperplasia involves a single limb.³ 

EPIDEMIOLOGY
Estimates of the incidence ofhemihyperplasia vary from 1 in 13,200 to 1 in 86,000.¹ The true incidence is difficult to determine because IHH can be very subtle and may not be diagnosed on routine physical examinations.

IHH is known to be associated with an increased risk of cancer.⁴ In a prospective, multicenter study of 168 children with IHH, 10 tumors developed in 9 patients for an estimated incidence of 5.9%.3 The tumors included Wilms tumor, adrenal carcinoma, hepatoblastoma, and leiomyosarcoma of the small bowel.³ The average age at the time of tumor detection was 36 months; about 95% of the tumors were located in the abdomen.³ Extra-abdominal tumors rarely occur but have been reported in the brain, testis, lung, uterus, and bone marrow.⁴

ETIOLOGY
The cause of IHH is unknown. However, in some patients with IHH, an imprinting defect of genes on chromosome 11p15.5 may be the cause.⁵ These same genes are involved in the development of Beckwith-Wiedemann syndrome. Abnormal imprinting may lead to the overexpression of paternal growth-promoting genes or the underexpression of maternal growth-inhibitory genes. This may result in hyperplasia and increased tumor risk.⁵

DIFFERENTIAL DIAGNOSIS
A thorough history and physical examination must be performed to determine whether a child’s hemihyperplasia is truly isolated or whether it is associated with an underlying syndrome or abnormality. Table 1 lists associated disorders.

COMPLICATIONS
Complications depend on the underlying cause of the hemihyperplasia and whether the hemihyperplasia is associated with a distinct clinical syndrome. The most significant comorbidity to consider is the development of malignancies (Table 2). Tumor risk is greatest in the first decade of life; thereafter, it declines to about the same risk as in the general population.⁵ Hemihyperplasia of a lower limb can lead to leg length discrepancy and result in pain, limping, and early degenerative bony changes as well as cosmetic problems and difficulty in fitting clothing and footwear.⁶

MANAGEMENT
Treatment of IHH is symptomatic and can include orthotics and braces; in severe cases, orthopedic surgical intervention may be warranted. Psychosocial support for the child also may be considered because hemihyperplasia can be associated with poor self-esteem and psychological stress.⁶

Continued screening for potential tumors is also an important part of management. Although creening recommendations vary, all focus on early detection of abdominal tumors because these are most frequently associated with IHH. Screening can include physical examinations and measurement of serum α₁-fetoprotein, serum chorionic gonadotropin, and urinary catecholamines (vanillylmandelic acid and homovanillic acid) every 4 months.⁴ Some recommend measurement of serum α₁-fetoprotein as frequently as every 6 weeks until age 4 years.⁵ It has been suggested that abdominal ultrasonography be performed every 3 months until age 8 years5 and that clinical surveillance for other tumors be considered.⁷ A complete blood cell count and chest radiography every 12 months until age 10 years also have been recommended.⁴

References:

REFERENCES:

1.

Heilstedt HA, Bacino CA. A case of familial isolated hemihyperplasia.

BMC Med Genet.

2004;5:1.

2.

Abraham P. What is the risk of cancer in a child with hemihypertrophy? Arch Dis Child. 2005;90:1312-1313.

3.

Hoyme HE, Seaver LH, Jones KL, et al. Isolated hemihyperplasia (hemihypertrophy): report of a prospective multicenter study of the incidence of neoplasia and review.

Am J Med Genet.

1998;79:274-278.

4.

Gracia Bouthelier R, Lapunzina P. Follow-up and risk of tumors in overgrowth syndromes.

J Pediatr Endocrinol Metab.

2005;18(suppl 1):1227-1235.

5.

Rao A, Rothman J, Nichols KE. Genetic testing and tumor surveillance for children with cancer predisposition syndromes.

Curr Opin Pediatr.

2008;20:1-7.

6.

Leung AK, Fong JH, Leong AG. Hemihypertrophy. J R Soc Health. 2002;122:24-27.

7.

Guala A, Pastore G, Fagioli F, et al. Hemihypertrophy and myelodysplasia.

Pediatr Blood Cancer.

2004;43:707-708.