Table II.

Main human hereditary lymphedema syndromes

Name Inheritance MIM number Main manifestations Mutated gene Candidate locus 
Syndromes with lymphedema as a primary manifestation 
Hereditary lymphedema IA (Milroy disease) Autosomal dominant with reduced penetrance 153100 Congenital lymphedema, chylous ascites caused by hypoplasia of lymphatic vessels FLT4 (VEGFR-3) 5q35.3 
Hereditary lymphedema IB Autosomal dominant with reduced penetrance 611944 Lymphedema of lower limbs, nature of lymphatic vascular defects is unknown Unknown 6q16.2–q22.1 
Hereditary lymphedema IC Autosomal dominant 613480 Lymphedema of limbs, age of onset 1–15 yr, nature of lymphatic vascular defects is unknown GJC2 (connexin47) 1q41–q42 
Hereditary lymphedema II (Meige disease) Unknown 153200 Puberty onset lymphedema, nature of lymphatic vascular defects is unknown Unknown Unknown 
Syndromes with lymphedema as a consistent feature 
Anhidrotic ectodermal dysplasia with immunodeficiency, osteopetrosis and lymphedema X-linked recessive 300301 Severe infections, osteopetrosis, nature of lymphatic vascular defects is unknown IKBKG (Nemo) TER420TRP Xq28 
Cholestasis-lymphedema syndrome (Aagenaes syndrome) Autosomal recessive 214900 Severe neonatal cholestasis, neonatal or childhood onset lymphedema caused by hypoplasia of lymphatic vessels Unknown 15q1 
Hennekam lymphangiectasia-lymphedema syndrome Autosomal recessive 235510 Lymphedema of limbs, intestinal lymphangiectasia, mental retardation, facial anomalies CCBE1 18q21.32 
HLT syndrome Autosomal dominant 607823 Alopecia, ectatic blood vessels, lymphedema, nature of lymphatic vascular defects is unknown SOX18 20q13.33 
Lymphedema, microcephaly, chorioretinopathy syndrome Autosomal dominant 152950 Congenital microcephaly and lymphedema, nature of lymphatic vascular defects is unknown Unknown Unknown 
Lymphedema-choanal atresia syndrome Autosomal recessive 608911 Blockage of nasal passage (choana), lymphedema of lower legs at 4–5 yr, nature of lymphatic vascular defects is unknown PTPN14 1q32–q41 
Lymphedema–distichiasis syndrome, yellow nail syndrome Autosomal dominant 153400/153300 Late onset leg lymphedema and metaplasia of Meibomian glands (distichiasis), impaired lymphatic drainage caused by incompetent lymphatic valves FOXC2 6q24.3 
Persistence of mullerian derivatives with lymphangiectasia and postaxial polydactyly (Urioste syndrome) Autosomal recessive? 235255 Intestinal and pulmonary lymphangiectasia, protein-losing entheropathy, polydactyly, and mullerian duct remnants Unknown Unknown 
Pulmonary congenital lymphangiectasia Unknown 265300 Congenital pulmonary lymphangiectasia, subcutaneous edema, nonimmune hydrops, chylothorax Unknown Unknown 
Name Inheritance MIM number Main manifestations Mutated gene Candidate locus 
Syndromes with lymphedema as a primary manifestation 
Hereditary lymphedema IA (Milroy disease) Autosomal dominant with reduced penetrance 153100 Congenital lymphedema, chylous ascites caused by hypoplasia of lymphatic vessels FLT4 (VEGFR-3) 5q35.3 
Hereditary lymphedema IB Autosomal dominant with reduced penetrance 611944 Lymphedema of lower limbs, nature of lymphatic vascular defects is unknown Unknown 6q16.2–q22.1 
Hereditary lymphedema IC Autosomal dominant 613480 Lymphedema of limbs, age of onset 1–15 yr, nature of lymphatic vascular defects is unknown GJC2 (connexin47) 1q41–q42 
Hereditary lymphedema II (Meige disease) Unknown 153200 Puberty onset lymphedema, nature of lymphatic vascular defects is unknown Unknown Unknown 
Syndromes with lymphedema as a consistent feature 
Anhidrotic ectodermal dysplasia with immunodeficiency, osteopetrosis and lymphedema X-linked recessive 300301 Severe infections, osteopetrosis, nature of lymphatic vascular defects is unknown IKBKG (Nemo) TER420TRP Xq28 
Cholestasis-lymphedema syndrome (Aagenaes syndrome) Autosomal recessive 214900 Severe neonatal cholestasis, neonatal or childhood onset lymphedema caused by hypoplasia of lymphatic vessels Unknown 15q1 
Hennekam lymphangiectasia-lymphedema syndrome Autosomal recessive 235510 Lymphedema of limbs, intestinal lymphangiectasia, mental retardation, facial anomalies CCBE1 18q21.32 
HLT syndrome Autosomal dominant 607823 Alopecia, ectatic blood vessels, lymphedema, nature of lymphatic vascular defects is unknown SOX18 20q13.33 
Lymphedema, microcephaly, chorioretinopathy syndrome Autosomal dominant 152950 Congenital microcephaly and lymphedema, nature of lymphatic vascular defects is unknown Unknown Unknown 
Lymphedema-choanal atresia syndrome Autosomal recessive 608911 Blockage of nasal passage (choana), lymphedema of lower legs at 4–5 yr, nature of lymphatic vascular defects is unknown PTPN14 1q32–q41 
Lymphedema–distichiasis syndrome, yellow nail syndrome Autosomal dominant 153400/153300 Late onset leg lymphedema and metaplasia of Meibomian glands (distichiasis), impaired lymphatic drainage caused by incompetent lymphatic valves FOXC2 6q24.3 
Persistence of mullerian derivatives with lymphangiectasia and postaxial polydactyly (Urioste syndrome) Autosomal recessive? 235255 Intestinal and pulmonary lymphangiectasia, protein-losing entheropathy, polydactyly, and mullerian duct remnants Unknown Unknown 
Pulmonary congenital lymphangiectasia Unknown 265300 Congenital pulmonary lymphangiectasia, subcutaneous edema, nonimmune hydrops, chylothorax Unknown Unknown 

References can be found under the corresponding Online Mendelian Inheritance of Man (MIM) entry.

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