Lymphedema-Distichiasis Syndrome

Excerpt

Clinical characteristics: Lymphedema-distichiasis syndrome (referred to as LDS in this GeneReview) is characterized by lower-limb lymphedema, and distichiasis (aberrant eyelashes ranging from a full set of extra eyelashes to a single hair). Lymphedema typically appears in late childhood or puberty, is confined to the lower limbs with or without involvement of the external genitalia, and is often asymmetric; severity varies within families. Males develop edema at an earlier age and have more problems with cellulitis than females. Distichiasis, which may be present at birth, is observed in 94% of affected individuals. About 75% of affected individuals have ocular findings including corneal irritation, recurrent conjunctivitis, and photophobia; other common findings include varicose veins and ptosis.

Diagnosis/testing: The clinical diagnosis of LDS is established in a proband with either lymphedema and distichiasis, distichiasis and a family history of lower-limb lymphedema, or lower-limb lymphedema and a family history of distichiasis. If clinical findings are not diagnostic, the identification of a heterozygous FOXC2 pathogenic variant by molecular genetic testing confirms the diagnosis.

Management: Treatment of manifestations: Lubrication, plucking, cryotherapy, electrolysis, or lid splitting for treatment of distichiasis; fitted compression garments and bandaging to improve swelling and discomfort associated with edema. To prevent secondary cellulitis, good skin care and prompt treatment of infected skin lesions; prompt treatment of cellulitis with antibiotics. The implementation of hosiery prior to the development of lymphedema may help reduce the extent of edema. Diuretics are not effective in the treatment of lymphedema.

Genetic counseling: LDS is inherited in an autosomal dominant manner. Approximately 75% of affected individuals have an affected parent; about 25% have a de novo pathogenic variant. Each child of an individual with LDS has a 50% chance of inheriting the pathogenic variant. Disease severity cannot be predicted and is variable even within the same family. If the FOXC2 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing are possible. Fetal echocardiography is recommended because of the increased risk for congenital heart disease, renal abnormalities, cleft palate, and hydrothoraces or hydrops fetalis.