Hypotrichosis–lymphedema–telangiectasia syndrome

Overview

Hypotrichosis–lymphedema–telangiectasia syndrome (HLTS) is a rare genetic disorder characterized by a triad of features: sparse or absent hair (hypotrichosis), swelling due to lymphatic dysfunction (lymphedema), and visible small dilated blood vessels near the surface of the skin (telangiectasia). The condition typically manifests in early childhood and involves abnormalities of the skin, hair, and lymphatic system. HLTS may occur as an isolated disorder or in association with other systemic issues, depending on the underlying genetic mutation.

Causes

HLTS is primarily caused by mutations in the SOX18 gene, which plays a critical role in the development of blood vessels, lymphatic vessels, and hair follicles. The condition is usually inherited in an autosomal dominant pattern, although autosomal recessive inheritance has also been reported in some cases. In some individuals, HLTS may occur sporadically due to a new mutation with no family history of the disorder.

Symptoms

The hallmark features of hypotrichosis–lymphedema–telangiectasia syndrome include:

Hair Abnormalities (Hypotrichosis)

• Sparse scalp hair present from infancy

• Loss of eyebrows and eyelashes in some cases

• Body hair may also be reduced or absent

Lymphatic Abnormalities (Lymphedema)

• Painless swelling of the lower limbs, usually beginning in childhood or adolescence

• Swelling may be asymmetrical and progressive

• Rarely, upper limb lymphedema may also occur

Vascular Abnormalities (Telangiectasia)

• Prominent small red or purple blood vessels visible on the face, upper chest, or mucous membranes

• May increase in number with age

In some individuals, additional findings such as varicose veins, delayed wound healing, or minor cardiac anomalies have been reported. The severity and combination of symptoms can vary between patients.

Diagnosis

Diagnosis of HLTS is based on clinical findings supported by genetic testing. Diagnostic steps may include:

• Physical examination: Identification of characteristic skin, hair, and limb changes

• Family history assessment: To determine inheritance pattern

• Lymphoscintigraphy: Imaging to assess lymphatic system function and confirm lymphedema

• Skin biopsy: May help confirm telangiectasia if needed

• Genetic testing: Identification of mutations in the SOX18 gene confirms the diagnosis

Early diagnosis is important to initiate supportive care and monitor for potential complications.

Treatment

There is no cure for HLTS, and treatment focuses on managing individual symptoms and improving quality of life. Management strategies include:

• Lymphedema management: Compression garments, manual lymphatic drainage, and physical therapy to reduce swelling

• Skin care: Moisturizers and sun protection to protect delicate skin and reduce irritation around telangiectasias

• Laser therapy: May be used cosmetically to reduce the appearance of telangiectasias

• Hair care and cosmetic solutions: Wigs, eyebrow tattooing, or cosmetic support for sparse hair

• Regular follow-up: Monitoring for progression of lymphedema and vascular anomalies

• Genetic counseling: Recommended for affected families to understand inheritance and risks for future children

Prognosis

The prognosis for individuals with HLTS varies depending on the severity of symptoms. Most people with the syndrome have a normal life expectancy. Lymphedema can lead to complications such as skin infections or reduced mobility if not managed effectively, while telangiectasias are primarily cosmetic. With early diagnosis and supportive care, individuals with HLTS can lead functional and fulfilling lives, though lifelong management may be necessary for symptom control.