Table 1 Genes implicated in isolated and syndromic lymphedema forms
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 |