Dermatologic disorders

Leg-Length Discrepancy and Hemangiomas in a 15-Month-Old Girl: What’s the Cause?

Adam Powell, MD

 

A 15-month-old girl presented to a pediatric clinic to establish care. Her previous pediatrician had noted leg-length discrepancy and a large hemangioma on the girl’s leg, prompting referral to pediatric hematology/oncology for further evaluation.

Isolated hemihyperplasia B

Isolated hemihyperplasia AMagnetic resonance imaging scans of her abdomen had revealed multiple hepatic hemangiomas, an enlarged right kidney, and increased right-sided subcutaneous fat.

Her past medical history was otherwise unremarkable, and there was no family history of similar findings or genetic conditions. She is the first child of nonconsanguineous parents.

Physical examination revealed the girl’s right lower extremity to be larger than the left in circumference and length (A). She had a rather large involuting hemangioma on the left lower extremity (B) and a small hemangioma on the right cheek. 

The rest of the physical examination findings were unremarkable. Growth and development were normal.

What’s causing these symptoms?

A. Klippel-Trénaunay syndrome

B. Proteus syndrome

C. Isolated hemihyperplasia

D. Neurofibromatosis type 1

(Answer and discussion on next page)

Answer: Isolated Hemihyperplasia

Based on the right-sided hemihyperplasia and multiple hemangiomas, the patient was referred to a clinical geneticist for diagnostic assistance to determine whether she met the criteria for Klippel-Trénaunay syndrome or had isolated hemihyperplasia. Based on a review of the medical record and physical examination findings, it was felt that the girl had isolated hemihyperplasia as opposed to her symptoms being part of a genetic syndrome. The geneticist recommended that the girl undergo serum α-fetoprotein level testing and abdominal ultrasonography every 3 months to screen for embryonal tumors.

Isolated hemihyperplasia AThe patient has since seen a pediatric orthopedic surgeon, who deferred surgical procedures for the leg-length discrepancy and instead will monitor the patient yearly. The girl also has been referred to a dermatologist for possible medical management of the hemangiomas.

Isolated hemihyperplasia, formerly called isolated hemihypertrophy, describes a congenital overgrowth disorder featuring asymmetry related to growth differences in bone, soft tissue, or both. The condition is very similar to other overgrowth syndromes such as Beckwith-Wiedemann syndrome, Proteus syndrome, Sotos syndrome and Klippel-Trénaunay syndrome.1 Isolated hemihyperplasia has no specific cause, although some patients have been found to have an imprinting defect of genes on 11p15.5.2 Because no specific genetic testing is available to diagnose isolated hemihyperplasia, a clinical geneticist often confirms the diagnosis after excluding other genetic overgrowth syndromes.

Patients with congenital overgrowth syndromes, including isolated hemihyperplasia, are at increased risk of developing embryonal tumors. One study of patients with isolated hemihyperplasia showed a lifetime tumor incidence of 5.9%, with approximately 90% of the tumors occurring in the abdomen.3 Due to this high tumor incidence rate, practice guidelines from the American College of Medical Genetics recommend a screening serum α-fetoprotein every 3 months until 4 years of age and abdominal ultrasonography every 3 months until 7 years of age.1

Isolated hemihyperplasia B

In addition, patients should have close follow-up with orthopedic surgery for the possible management of significant leg-length discrepancy as well as for scoliosis surveillance.4

Klippel-Trénaunay syndrome is diagnosed based on the triad of combined vascular malformations of the capillary, venous, and lymphatic tracts, varicosities of unusual distribution, and limb enlargement.5 The vascular malformations have been described as distinct from hemangiomas, which is why this patient did not meet criteria for this syndrome. Hemangiomas have endothelial hyperplasia with rapid postnatal growth followed by spontaneous involution. In contrast, vascular malformations have a flat endothelium that adjusts with the growth of the child.6 The lower limb is involved in more than 95% of Klippel-Trénaunay syndrome cases.5

While there appear to be differences in clinical practice, the current recommendation is that patients with Klippel-Trénaunay syndrome do not need routine screening for embryonal tumors.7

 

Adam Powell, MD, is a pediatrician at the Shaw Air Force Base Pediatric Clinic in South Carolina. The opinions expressed herein are those of the author and are not necessarily representative of those of Shaw Air Force Base, the Department of Defense, or the United States Army, Navy, or Air Force.

References

1. Clericuzio CL, Martin RA. Diagnostic criteria and tumor screening for individuals with isolated hemihyperplasia. Genet Med. 2009;11(3):220-222.

2. Rao A, Rothman J, Nichols KE. Genetic testing and tumor surveillance for children with cancer predisposition syndromes. Curr Opin Pediatr. 2008;20(1):1-7.

3. Hoyme HE, Seaver LH, Jones KL, Procopio F, Crooks W, Feingold M. Isolated hemihyperplasia (hemihypertrophy): report of a prospective multicenter study of the incidence of neoplasia and review. Am J Med Genet. 1998;79(4):274-278.

4. Stoll C, Alembik Y, Steib JP, De Saint-Martin A. Twelve cases with hemihypertrophy: etiology and follow up. Genet Couns. 1993;4(2):119-126.

5. Berry SA, Peterson C, Mize W, et al. Klippel-Trenaunay syndrome. Am J Med Genet. 1998;79(4):319-326.

6. Cohen MM Jr. Klippel-Trenaunay syndrome. Am J Med Genet. 2000; 93(3):171-175.

7. Greene AK, Kieran M, Burrows PE, Mulliken JB, Kasser J, Fishman SJ. Wilms tumor screening is unnecessary in Klippel-Trenaunay syndrome. Pediatrics. 2004;113(4):e326-e329.