Primary lymphoedema conditions, including genetic basis and inheritance, onset and nature of lymphoedema and associated features
| Condition | Genetic basis | Inheritance | Onset and nature of lymphedema | Associated features |
|---|---|---|---|---|
| Turner syndrome | 45,X (or similar) | Sporadic | Congenital (may be prenatal), hands and feet | Short 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, MAP2K1 | AD | Congenital (may be prenatal), lower limb Later onset genital oedema, chylous reflux, intestinal lymphangiectasia, and/or chylothoraces | Short stature, webbed neck, CHD (pulmonary stenosis or hypertrophic cardiomyopathy), dysmorphic features, bleeding tendency, intellectual disability, cryptorchid testes, pectus deformities |
| Hennekam syndrome | CCBE1 | AR | Congenital, multi-segment, facial, lymphangiectasia | Microcephaly, 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 | PIEZO1 | AR | Non-immune hydrops, childhood onset multisegment | Systemic involvement (chylothoraces and/or pericardial effusions) |
| EPHB4-related lymphatic-related hydrops | EPHB4 | AD | Non-immune hydrops | Atrial septal defects |
| PIK3CA-related overgrowth spectrum (PROS) | PI3K/AKT/mTOR pathway | Somatic | Congenital | Hypertrophy/overgrowth of bone and soft tissues resulting in asymmetry, vascular malformations, naevi/pigmentation |
| Milroy syndrome | VEGFR3, VEGFC | AD | Congenital, pedal, lower limb | Hydrocele, prominent veins, upslanting toenails, papillomatosis, and urethral abnormalities in males |
| Microcephaly-chorioretinopathy-lymphedema-mental retardation (MCLMR) | KIF11 | AD | Congenital, lower limb | Microcephaly, chorioretinopathy, intellectual disability, epilepsy, CHD |
| Lymphedema distichiasis | FOXC2 | AD | Pubertal, lower limb | Distichiasis, varicose veins, ptosis, cleft palate, CHD, renal anomalies |
| Emberger syndrome | GATA2 | AD | Childhood, lower limb and/or genital | Myelodysplasia, sensorineural hearing loss |
| Primary lymphedema | GJC2 | AD | Childhood/adolescence or postnatal, four limb |
Genes written in italics. AD = autosomal dominant; AR = autosomal recessive; CHD = congenital heart disease.