Table 1.

Primary lymphoedema conditions, including genetic basis and inheritance, onset and nature of lymphoedema and associated features

ConditionGenetic basisInheritanceOnset and nature of lymphedemaAssociated features
Turner syndrome45,X (or similar)SporadicCongenital (may be prenatal), hands and feetShort stature, webbed neck, widely spaced nipples and increased carrying angle, CHD (coarctation of aorta), renal anomalies, primary infertility, mild intellectual disability
Noonan syndrome>23 rasopathy genes including: PTPN11, SOS1, RAF1, RIT1, KRAS, NRAS, BRAF, MAP2K1ADCongenital (may be prenatal), lower limb Later onset genital oedema, chylous reflux, intestinal lymphangiectasia, and/or chylothoracesShort stature, webbed neck, CHD (pulmonary stenosis or hypertrophic cardiomyopathy), dysmorphic features, bleeding tendency, intellectual disability, cryptorchid testes, pectus deformities
Hennekam syndrome CCBE1ARCongenital, multi-segment, facial, lymphangiectasiaMicrocephaly, distinct facial features, intellectual disability, short stature, respiratory problems, skeletal anomalies, anaemia, polysplenia, renal anomalies. Systemic lymphatic involvement
PIEZO1-related lymphatic-related hydrops/generalised lymphatic dysplasia PIEZO1ARNon-immune hydrops, childhood onset multisegmentSystemic involvement (chylothoraces and/or pericardial effusions)
EPHB4-related lymphatic-related hydrops EPHB4ADNon-immune hydropsAtrial septal defects
PIK3CA-related overgrowth spectrum (PROS)PI3K/AKT/mTOR pathwaySomaticCongenitalHypertrophy/overgrowth of bone and soft tissues resulting in asymmetry, vascular malformations, naevi/pigmentation
Milroy syndrome VEGFR3, VEGFCADCongenital, pedal, lower limbHydrocele, prominent veins, upslanting toenails, papillomatosis, and urethral abnormalities in males
Microcephaly-chorioretinopathy-lymphedema-mental retardation (MCLMR) KIF11ADCongenital, lower limbMicrocephaly, chorioretinopathy, intellectual disability, epilepsy, CHD
Lymphedema distichiasis FOXC2ADPubertal, lower limbDistichiasis, varicose veins, ptosis, cleft palate, CHD, renal anomalies
Emberger syndrome GATA2ADChildhood, lower limb and/or genitalMyelodysplasia, sensorineural hearing loss
Primary lymphedemaGJC2ADChildhood/adolescence or postnatal, four limb
  • Genes written in italics. AD = autosomal dominant; AR = autosomal recessive; CHD = congenital heart disease.