An approach to familial lymphoedema

Abstract

Lymphoedema is the build-up of lymphatic fl uid leading to swelling in the tissues. Most commonly it affects the peripheries. Diagnosis is based on clinical assessment and imaging with lymphoscintigraphy. Treatment is supportive with compression garments, massage, good skin hygiene and prompt use of antibiotics to avoid the complication of cellulitis. Most commonly, lymphoedema occurs as a result of damage to the lymphatic system following surgery, trauma, radiation or infection. However, it can be primary, often associated with a genetic defect that causes disruption to the development of the lymphatic system. Common genetic conditions associated with lymphoedema include Turner syndrome and Noonan syndrome; however, there are numerous others that can be classifi ed based on their clinical presentation and associated features. Herein we discuss how to diagnose and classify the known primary lymphoedema conditions and how best to investigate and manage this group of patients.

Unilateral Primary Congenital Lymphedema of the Upper Limb in an 11-Month-Old Infant: A Clinical and Pharmacological Perspective

“…Primary lymphedema has an estimated prevalence of 1.15 per 100000 [ 5 ]. It is categorised according to the age of onset as congenital (before two years), praecox (before 35 years), and tarda (after 35 years) [ 1 ] [ 2 ]. Isolated involvement of one of the upper limbs is one of the rarest forms of congenital lymphedema as 92 % of cases of congenital lymphedema involve the lower extremities [ 4 ] [ 6 ].…”

“…Also, adipose-derived stem cells have shown potential in lymphedema therapy [ 12 ]. Drugs targeting the PI3/AKT/mTOR signalling pathway such as mechanistic target of rapamycin inhibitors are also being evaluated for reducing lymphedema in some somatic overgrowth disorders [ 2 ]. Leukotriene B4 affects lymphangiogenesis in animal models and is elevated in patients with lymphedema.…”

“…Primary lymphedema results from developmental abnormalities leading to pathological lymphatics. Secondary lymphedema is an acquired dysfunction of normally developed lymphatics [ 1 ] [ 2 ]. Congenital subtype of primary lymphedema is defined as swelling that has an onset at birth up to two years [ 3 ].…”

Fetal hydrops – a review and a clinical approach to identifying the cause

“…The PIEZO1 gene encodes a highly conserved, large transmembrane protein that is a mechanically activated cation channel [114]. Postnatally affected individuals, in addition to widespread lymphoedema, may have systemic complications including pulmonary lymphangiectasia, pleural effusions chylothoraces and pericardial effusions [104]. Autosomal dominant gainof-function mutations in PIEZO1 cause dehydrating hereditary stematocytosis which can also present with a severe fetal hydrops/ perinatal oedema phenotype [110] Heterozygous mutations in EPHB4 have been shown to cause non-immune fetal hydrops and with extensive fetal morbidity [115].…”

CHAPLE syndrome uncovers the primary role of complement in a familial form of Waldmann's disease

“…Detailed discussions of lymphatic development or familial lymphedema syndromes are beyond the scope of this mini‐review and readers are referred to reviews by Jha et al and Jones et al …”