Hemihyperplasia–multiple lipomatosis syndrome

Overview

Hemihyperplasia–multiple lipomatosis syndrome (HHML) is a rare congenital disorder characterized by asymmetric overgrowth of one side of the body (hemihyperplasia) along with the development of multiple subcutaneous lipomas (benign fatty tumors). This condition is considered part of a spectrum of overgrowth syndromes and may overlap with other disorders such as Proteus syndrome or Bannayan-Riley-Ruvalcaba syndrome. HHML typically presents in early childhood and may affect a variety of tissues, including the skin, soft tissue, and sometimes internal organs.

Causes

The exact cause of HHML syndrome remains unknown, and it is considered a sporadic condition in most cases. Some researchers suspect a genetic or epigenetic basis involving somatic mosaicism, where mutations affect only certain cells or tissues in the body. Unlike other overgrowth syndromes, no single gene has been definitively linked to HHML. However, some cases may show similarities to disorders caused by PTEN mutations or other growth-regulating pathways.

Symptoms

The hallmark features of HHML syndrome include:

• Hemihyperplasia: Unilateral overgrowth of the limbs, face, or trunk

• Multiple lipomas: Soft, movable, fatty tumors found beneath the skin, typically non-painful

• Asymmetry in limb size, girth, or length

• Possible skeletal deformities or skin changes on the affected side

• Rarely, internal lipomas or organomegaly (enlargement of internal organs)

In most cases, cognitive development is normal, and systemic complications are minimal, but the cosmetic and functional impact can vary significantly between individuals.

Diagnosis

Diagnosis of HHML syndrome is clinical, based on the presence of the characteristic signs. The diagnostic process may include:

• Physical examination: Assessing body asymmetry and identifying lipomas

• Imaging studies: Ultrasound, MRI, or CT to evaluate internal structures and lipomas

• Genetic testing: May be conducted to rule out overlapping syndromes like PTEN hamartoma tumor syndrome or Proteus syndrome

• Biopsy: Rarely needed but can confirm the benign nature of lipomas

Early evaluation is important to differentiate HHML from other overgrowth disorders that may carry a higher risk of malignancy.

Treatment

There is no specific cure for HHML syndrome, and treatment is focused on managing symptoms and improving quality of life. Options include:

• Monitoring: Regular follow-up to monitor growth patterns and the appearance of new lipomas

• Surgical removal: Lipomas may be excised if they cause discomfort, limit movement, or lead to cosmetic concerns

• Orthopedic care: To manage limb-length discrepancies or postural issues due to asymmetry

• Physical therapy: To improve function and mobility in affected limbs

In general, the management approach is conservative unless symptoms significantly affect the patient's daily life.

Prognosis

The prognosis for individuals with Hemihyperplasia–multiple lipomatosis syndrome is generally favorable. The condition is typically benign, with no known association with malignant transformation of the lipomas. However, close clinical monitoring is recommended to detect any potential complications, such as rapid growth or structural deformities. Most individuals lead normal lives, though surgical interventions may be required for functional or aesthetic reasons. Psychological support may also be beneficial for individuals affected by visible asymmetry or recurrent procedures.