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Table 1 Genes implicated in isolated and syndromic lymphedema forms

From: Primary lymphedema French National Diagnosis and Care Protocol (PNDS; Protocole National de Diagnostic et de Soins)

Syndrome OMIM number Associated clinical signs (non-exhaustive list) Gene(s) implicated Inheritance Estimated prevalence (Orphanet 2018)
Milroy syndrome #153100 FLT4/VEGFR3 AD 1/2500 to 1/10,000
Milroy-like syndrome #615907 VEGFC AD < 1/100,000
Meige syndrome #613480 GJC2 AD < 1/100,000
Turner syndrome (X-monosomy)   Short stature
Ovarian insufficiency
Bone anomalies
Deafness
Cardiovascular malformations
Digestive malformations
Cardiac malformations
de novo 1/2500 to 1/10,000
Down syndrome (trisomy 21) #190685 Facial dysmorphy
Digestive malformations
Skeletal malformations
Cardiac malformations
Extremities anomalies
Hypotony
AD 1/2500 to 1/10,000
Noonan syndrome types 1 and 4 #163950
#610733
Arterial pulmonary stenosis
Facial dysmorphy
Pterygium colli (webbed neck)
Learning difficulties
PTPN11
SOS1
AD 1/2500 to 1/10,000
CM-AVM syndrome #608354 Capillary malformations
Arteriovenous malformations
RASA1 AD/mosaic 1/10,000 to 1/100,000
Lymphedema–distichiasis #153400
#153300
Distichiasis
Ungual dystrophy
FOXC2 AD 1/10,000 to 1/100,000
Emberger’s syndrome #614038 Facial dysmorphy
Deafness
Pancytopenia
Myelodysplasia
MET
HGF
GATA2
AD 1/100,000 to 1/1,000,000
Aagenaes syndrome #214900 Neonatal cholestatic liver disease
Hepatomegaly
Jaundice
Cirrhosis
Splenomegaly
Infantile malabsorption
15q AR < 1/1,000,000
Microcephaly syndrome 152950 Facial dysmorphia
Microcephaly
Learning difficulties
Retinopathy
KIF11 AD (de novo) 1/100,000 to 1/1,000,000
Hennekam syndrome #235510 Intestinal lymphangiectasia
Exudative enteropathy
Learning difficulties
Deafness
Cardiac, renal, extremity malformations
CCBE1 AR < 1/1000,000
Van Maldergem’s syndrome (type 2) # 615546 Facial dysmorphia
Learning difficulties
Deafness
Genitourinary malformations
FAT4 AR < 1/1000,000
Hereditary lymphedema type III #616843 Facial dysmorphia
Deafness
Learning difficulties
Lymphangiectasia
PIEZO1 AR < 1/1,000,000
Oculodentodigital dysplasia #16420 Facial dysmorphy
Microcephaly
Psychomotor retardation
Neurological involvement
Deafness
Ophthalmological abnormalities (microphthalmia, cataract…)
Dental anomalies
Cardiac malformations
Extremity anomalies
GJA1 AD (de novo) < 1/1,000,000
Lymphedema-choanal atresia #613611 Choanal atresia PTPN14 AR < 1/1,000 000
OLEDAID syndrome #300301 Ectodermic dysplasia
Osteopetrosis
Immunodeficiency
IKBKG/NEMO XLR < 1/1,000,000
Hypotrichosis–lymphedema–telangiectasia syndrome #607823
#137940
Facial dysmorphia
Hypotrichosis of the scalp and face
Telangiectasia
Glomerulosclerosis
SOX18 AR/AD < 1/1,000,000
  1. AD autosomal dominant, AR autosomal recessive, OLEDAID osteopetrosis–lymphedema–ectodermal dysplasia anhidrotic with immunodeficiency, XLR X-linked recessive