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  1. NGS Panel – Genetic Testing for Noonan Syndrome

Noonan Syndrome

June 27, 2017

Disease synonyms

Noonan - CFC Syndrome, NS, Rasopathies


Inheritance pattern

Autosomal dominant


Clinical features

Noonan syndrome (NS) is a rare autosomal dominant disease characterized by short stature, characteristic facies, congenital heart defect, and developmental delay. NS is one of the most common birth defects, with an estimated incidence of 1 in 1,000 to 1 in 2,500 births 1.

Noonan syndrome Infographics

Noonan syndrome belongs to the group of diseases called “RASopathies” e.g. disorders of development characterized by broad clinical and geneticc heterogeneity. RASopathies are caused by germline mutations in those genes that encode RAS family of proteins, e.g. mitogen-activated protein kinases, protein that control signal transduction, participate in development and tumorigenesis, and they include the following conditions (among others):

  • Noonan syndrome (NS)
  • Cardiofaciocutaneous syndrome (CFC syndrome)
  • Noonan syndrome with multiple lentigines, also known as LEOPARD syndrome (LS)
  • Costello syndrome (CS)
  • Neurofibromatosis type 1 (NF1)
  • Legious Syndrome (NF-1 like)
  • Autoimmune lymphoproliferative syndrome (ALPS)

Noonan syndrome (NS) is characterized by characteristic facial features and short stature, specific cardiological features and other signs and symptoms. In many cases those affected with NS prenatal features could be diagnosed based on common perinatal findings, such as lymphatic dysplasia, polyhydramnios, cystic hygroma, renal and/or cardiac anomalies, and others 2. Newborn infants with NS usually have feeding problems resulting in poor growth and delayed bone growth. Finally, more than 50% of all affected females and 40% of affected males have an adult height that is below the third centile 3.

Major clinical features, suggestive of a clinical diagnosis of Noonan syndrome, include the following:

Characteristic facies including:

  • Triangular-shaped face
  • Down-slanting palpebral fissures
  • Ptosis (drooping of the upper eyelid)
  • Strabismus (48%) (“crossed eyes”) 4
  • Amblyopia (33%) (“lazy eye” e.g. reduced vision in one eye) 4
  • Refractive errors (61%)4
  • Hypertelorism (unusual distance between eyes)
  • Low-set ears with thickened helices
  • High nasal bridge
  • Short, webbed neck

Ocular features frequently observed in NS-patients include the following: Hypertelorism and eyelid abnormalities, amblyopia, myopia, astigmatism, strabismus, limited ocular motility, prominent corneal nerves, abnormal stereopsis, and posterior embryotoxon 4.

Auditory features include progressive high-frequency sensorineural hearing loss, in many cases as high as 50% 5. Early monitoring of hearing quality is important for young NS-patients in order to prevent speech abnormalities. Chest/back abnormalities are common in NS-patients in a form of pectus carinatum and/or excavatum and scoliosis.

Cardiac defects occur in up to 80% of Noonan syndrome patients 1, 6, including pulmonary stenosis, dysplastic pulmonary valve, hypertrophic cardiomyopathy, atrial and ventricular septal defects, and others.

Skin findings observed in Noonan patients include:

  • Lymphedema1
  • Prominent pads of fingers and toes (67%) 1
  • Follicular keratosis of the face and extensor surfaces (14%)1
  • Multiple lentigines (3%)1

Neurologic findings include the following:

  • Hypotonia1
  • Seizure disorder (13%)1
  • Unexplained peripheral neuropathy (infrequent) 1

Further signs and symptoms of Noonan syndrome include hepatosplenomegaly, genitourinary features, renal anomalies and skeletal features 1, 6. Joint laxity is present in more than half of patients as well as talipes equinovarus, radioulnar synostosis, cervical spine fusion, and joint contractures 1, 6.

Affected individuals clinically diagnosed with Noonan syndrome have normal chromosome studies. However, molecular genetic testing has identified a pathogenic variant in several genes that are now proven to be associated with Noonan syndrome. These genes are included in CENTOGENE´s Noonan - CFC syndrome panel (BRAF, CBL, HRAS, KAT6B, KRAS, LZTR1, MAP2K1, MAP2K2, NF1, NRAS, PTPN11, RAF1, RASA2, RIT1, SHOC2, SOS1, SOS2, SPRED1; see Table).

Mutations in PTPN11 are identified in approximately 50% of affected individuals 21. About 16-20% of individuals with a clinical diagnosis of NS who do not have an identified PTPN11 pathogenic variant are found to have an SOS1 pathogenic variant 21, 25. Furthermore, the frequency of NS-causing mutations in the SOS1 gene is about 13% 21, in the RAF1 and RIT1 genes about 5% each 22, and in the KRAS gene fewer than 5% 14, 15.

The KRAS-related NS phenotype tends to be atypical, with severe intellectual disability, and unusual feature of craniosynostosis in rare cases. Only few individuals with an NRAS pathogenic variant have been reported with a NS phenotype. The clinical features appear to be typical with no particular or distinctive phenotype observed.

Other genes in which mutations have been reported to cause Noonan syndrome in less than 1% of cases include NRAS, BRAF, KAT6B, MAP2K1, MAP2K2, NF1, and others.


Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
ABCC6 603234 Pseudoxanthoma elasticum, forme fruste; Pseudoxanthoma elasticum; generalized arterial calcification of infancy type 2 AD, AR 19
ACTA2 102620 Aortic aneurysm, familial thoracic 6; Multisystemic smooth muscle dysfunction syndrome; Moyamoya disease 5 AD 5
ADAMTS2 604539 Ehlers-Danlos syndrome dermatosparaxis type AR 9
ADAMTSL2 612277 Geleophysic dysplasia 1 AR 7
ALDH18A1 138250 Cutis laxa, autosomal recessive, type IIIA; Spastic paraplegia 9A, autosomal dominant; spastic paraplegia 9B; Cutis laxa, autosomal dominant 3 AD, AR 11
ATP6V0A2 611716 autosomal recessive cutis laxa type IIA; Wrinkly skin syndrome AR 1
ATP7A 300011 X-linked distal spinal muscular atrophy type 3; Occipital horn syndrome; Menkes disease XLR 30
B3GALT6 615291 Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures; Ehlers-Danlos syndrome spondylodysplastic type 2 AR 9
B3GAT3 606374 Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects AR 5
B4GALT7 604327 Ehlers-Danlos syndrome spondylodysplastic type 1 AR 2
BGN 301870 Meester-Loeys syndrome XL, XLR 2
CBS 613381 homocystinuria with or without response to pyridoxine AR 29
CHST14 608429 Ehlers-Danlos syndrome musculocontractural type 1 AR 5
COL11A1 120280 Marshall syndrome; Fibrochondrogenesis 1; Stickler syndrome 2 AD, AR 48
COL11A2 120290 Stickler syndrome, type III; Otospondylomegaepiphyseal dysplasia; Deafness, autosomal dominant 13; Deafness, autosomal recessive 53; Fibrochondrogenesis 2 AD, AR 38
COL12A1 120320 Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 AD 29
COL1A1 120150 Caffey disease; Ehlers-Danlos syndrome arthrochalasia type 1; osteogenesis imperfecta type 1; osteogenesis imperfecta type 2; osteogenesis imperfecta type 4; OSTEOPOROSIS; osteogenesis imperfecta type 3 AD 63
COL1A2 120160 osteogenesis imperfecta type 2; osteogenesis imperfecta type 4; OSTEOPOROSIS; Ehlers-Danlos syndrome, cardiac valvular form; osteogenesis imperfecta type 3; Ehlers-Danlos syndrome arthrochalasia type 2 AD, AR 52
COL2A1 120140 Epiphyseal dysplasia, multiple, with myopia and deafness; Legg-Calve-Perthes disease; Platyspondylic skeletal dysplasia, Torrance type; Kniest dysplasia; congenital spondyloepiphyseal dysplasia; SMED Strudwick type; Achondrogenesis, type II or hypochondrogenesis; Spondyloperipheral dysplasia; Osteoarthritis with mild chondrodysplasia; Avascular necrosis of the femoral head; Czech dysplasia; Stickler syndrome type 1; Stanescu type spondyloepiphyseal dysplasia AD 38
COL3A1 120180 vascular-type Ehlers-Danlos syndrome AD, AR 31
COL5A1 120215 Ehlers-Danlos syndrome classic type 1 AD 91
COL5A2 120190 Ehlers-Danlos syndrome classic type 2 AD 36
COL9A1 120210 Stickler syndrome, type IV; Epiphyseal dysplasia, multiple, 6 AD 17
COL9A2 120260 Stickler syndrome, type V AD, AR 12
COL9A3 120270 multiple epiphyseal dysplasia type 3 AD 6
CREB3L1 616215 osteogenesis imperfecta type 16 AR 5
DSE 605942 Ehlers-Danlos syndrome musculocontractural type 2 AR 2
EFEMP2 604633 Cutis laxa, autosomal recessive, type IB AR 2
ELN 130160 Cutis laxa, autosomal dominant 1, ADCL1; Supravalvar aortic stenosis AD 6
FBLN5 604580 Cutis laxa, autosomal recessive, type IA; hereditary neuropathy with or without age-related macular degeneration AD, AR 1
FBN1 134797 Marfan syndrome; stiff skin syndrome; Weill-Marchesani syndrome 2; geleophysic dysplasia 2; Marfan lipodystrophy syndrome AD 76
FBN2 612570 congenital contractural arachnodactyly; early-onset macular degeneration AD 39
FKBP14 614505 Ehlers-Danlos syndrome kyphoscoliotic type 2 AR 3
FLCN 607273 colorectal cancer; Birt-Hogg-Dube syndrome; Renal carcinoma, chromophobe, somatic; primary spontaneous pneumothorax AD 11
FLNA 300017 Congenital short bowel syndrome; Heterotopia, periventricular / X-linked periventricular heterotopia; Terminal osseous dysplasia; FG syndrome 2; Otopalatodigital syndrome, type II; Frontometaphyseal dysplasia; Melnick-Needles syndrome; otopalatodigital syndrome type I; Cardiac valvular dysplasia, X-linked XL, XLD, XLR 39
FOXE3 601094 Anterior segment dysgenesis 2, multiple subtypes; Cataract 34, multiple types AD, AR 0
GORAB 607983 geroderma osteodysplasticum AR 2
ITGB4 147557 Epidermolysis bullosa simplex, Weber-Cockayne type; junctional epidermolysis bullosa, non-Herlitz type; epidermolysis bullosa with pyloric atresia AD, AR 3
KCNJ13 603208 AD, AR 0
LAMA3 600805 junctional epidermolysis bullosa, non-Herlitz type; junctional epidermolysis bullosa, Herlitz-type; laryngoonychocutaneous syndrome AR 30
LAMB3 150310 amelogenesis imperfecta type IA; junctional epidermolysis bullosa, non-Herlitz type; junctional epidermolysis bullosa, Herlitz-type AD, AR 20
LAMC2 150292 junctional epidermolysis bullosa, non-Herlitz type; junctional epidermolysis bullosa, Herlitz-type AR 5
LOX 153455 thoracic aortic aneurysm type 10 AD 1
LRP2 600073 Donnai-Barrow syndrome AR 10
MAT2A 601468 0
MBTPS2 300294 IFAP syndrome with or without BRESHECK syndrome; Keratosis follicularis spinulosa decalvans, X-linked XLR 4
MED12 300188 Opitz-Kaveggia syndrome /FG syndrome-1; Lujan-Fryns syndrome XLR 16
MFAP5 601103 AD 0
MYH11 160745 familial thoracic aortic aneurysm 4 AD 25
MYLK 600922 Aortic aneurysm, familial thoracic 7 AD, AR 20
NOTCH1 190198 aortic valve disease type 1; Adams-Oliver syndrome 5 AD 12
PLOD1 153454 Ehlers-Danlos syndrome kyphoscoliotic type 1 AR 22
PRDM5 614161 Brittle Cornea Syndrome 2 AR 2
PRKG1 176894 familial thoracic aortic aneurysm type 8 AD 1
PYCR1 179035 autosomal recessive cutis laxa type 2B AR 3
RIN2 610222 MACS syndrome AR 1
SKI 164780 Shprintzen-Goldberg Craniosynostosis Syndrome AD 3
SLC2A10 606145 arterial tortuosity syndrome AR 9
SLC39A13 608735 Ehlers-Danlos syndrome spondylodysplastic type 3 AR 2
SMAD2 601366 2
SMAD3 603109 Loeys-Dietz syndrome 3 AD 6
SMAD4 600993 Myhre syndrome; Juvenile polyposis syndrome, infantile form; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome; Pancreatic Cancer AD 3
SMAD6 602931 Aortic valve disease 2; Craniosynostosis type 7 AD 4
SP7 606633 osteogenesis imperfecta type 12 AR 2
TGFB2 190220 Loeys-Dietz syndrome 4 AD 5
TGFB3 190230 Arrhythmogenic right ventricular dysplasia 1; Loeys-Dietz syndrome 5 AD 12
TGFBR1 190181 Multiple Self-Healing Squamous Epithelioma, Susceptibility To; Loeys-Dietz syndrome 1 AD 8
TGFBR2 190182 Esophageal cancer, somatic; Loeys-Dietz syndrome 2; Colorectal cancer, hereditary nonpolyposis, type 6 AD 5
TNXB 600985 classic-like Ehlers-Danlos syndrome; Vesicoureteral reflux type 8 AD, AR 83
VCAN 118661 Wagner syndrome 1 AD 9
WNT1 164820 osteogenesis imperfecta type 15; susceptibility to early-onset autosomal dominant osteoporosis AR 3
ZNF469 612078 Brittle cornea syndrome AR 10

Gene OMIM (Gene) Associated diseases (OMIM) Inheritance CentoMD® exclusive variant numbers (++)
ABCB6 605452 Dyschromatosis universalis hereditaria 3 AD 4
ABCC6 603234 Pseudoxanthoma elasticum, forme fruste; Pseudoxanthoma elasticum; generalized arterial calcification of infancy type 2 AD, AR 19
ACTA1 102610 Myopathy, nemaline, 3; Myopathy, congenital, with fiber-type disproportion AD, AR 27
ACTA2 102620 Aortic aneurysm, familial thoracic 6; Multisystemic smooth muscle dysfunction syndrome; Moyamoya disease 5 AD 5
ACTB 102630 Baraitser-Winter syndrome 1; Dystonia, juvenile-onset AD 11
ACTG1 102560 Deafness, Autosomal Dominant 20; Baraitser-Winter syndrome 2 AD 7
ACVR2B 602730 Heterotaxy, visceral, 4, autosomal 1
ADAMTS2 604539 Ehlers-Danlos syndrome dermatosparaxis type AR 9
ADAMTSL2 612277 Geleophysic dysplasia 1 AR 7
ADGRG1 604110 bilateral frontoparietal polymicrogyria; bilateral perisylvian polymicrogyria AR 11
AFF4 604417 CHOPS syndrome AD 2
AGPS 603051 rhizomelic chondrodysplasia punctata type 3 AR 7
AGRN 103320 congenital myasthenic syndrome type 8, with pre- and postsynaptic defects AR 34
AHI1 608894 Joubert syndrome 3 AR 16
AKT3 611223 Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 AD 2
ALDH18A1 138250 Cutis laxa, autosomal recessive, type IIIA; Spastic paraplegia 9A, autosomal dominant; spastic paraplegia 9B; Cutis laxa, autosomal dominant 3 AD, AR 11
ALDH1A3 600463 isolated microphthalmia 8 AR 10
ALG2 607905 congenital disorder of glycosylation type 1i AR 2
ALPL 171760 adult hypophosphatasia; infantile hypophosphatasia; childhood-onset hypophosphatasia AD, AR 40
AMPD2 102771 pontocerebellar hypoplasia 9 AR 9
ANKH 605145 Chondrocalcinosis 2; Craniometaphyseal dysplasia AD 3
ANKRD11 611192 KBG syndrome AD 39
ANO5 608662 gnathodiaphyseal dysplasia; limb-girdle muscular dystrophy type 2L AD, AR 8
AP4M1 602296 autosomal recessive spastic paraplegia type 50 AR 11
ARFGEF2 605371 Periventricular heterotopia with microcephaly AR 8
ARHGAP31 610911 Adams-Oliver syndrome 1 AD 12
ARID1A 603024 Coffin-Siris syndrome type 2 AD 20
ARID1B 614556 Coffin-Siris syndrome 1 AD 64
ARL13B 608922 Joubert syndrome 8 AR 2
ARL6 608845 Bardet-Biedl syndrome type 1; Bardet-Biedl syndrome 3; Retinitis pigmentosa 55 AR, DiR 6
ARMC4 615408 primary ciliary dyskinesia, 23 AR 2
ARSL 300180 Chondrodysplasia punctata, X-linked recessive XLR 3
ARX 300382 Proud syndrome; X-linked lissencephaly-2; ARX- related mental retardation; early infantile epileptic encephalopathy 1; Partington X-Linked Mental Retardation Syndrome XL, XLR 11
ASPM 605481 primary microcephaly 5 AR 18
ASXL1 612990 Bohring-Opitz syndrome; Myelodysplastic syndrome, somatic AD 13
ASXL3 615115 Bainbridge-Ropers syndrome AD 17
ATP6V0A2 611716 autosomal recessive cutis laxa type IIA; Wrinkly skin syndrome AR 1
ATP7A 300011 X-linked distal spinal muscular atrophy type 3; Occipital horn syndrome; Menkes disease XLR 30
ATR 601215 Seckel syndrome 1; ?Cutaneous telangiectasia and cancer syndrome, familial AD, AR 15
ATRX 300032 Alpha-Thalassemia Myelodysplasia Syndrome; Alpha-Thalassemia/Mental Retardation Syndrome, X-Linked; Mental retardation-hypotonic facies syndrome, X-linked XLD, XLR 16
B3GALNT2 610194 congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A11 AR 5
B3GALT6 615291 Spondyloepimetaphyseal dysplasia with joint laxity, type 1, with or without fractures; Ehlers-Danlos syndrome spondylodysplastic type 2 AR 9
B3GAT3 606374 Multiple joint dislocations, short stature, craniofacial dysmorphism, and congenital heart defects AR 5
B4GALT7 604327 Ehlers-Danlos syndrome spondylodysplastic type 1 AR 2
B4GAT1 605517 congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies A13 AR 2
B9D1 614144 Meckel Syndrome, Type 9 AR 11
B9D2 611951 Meckel syndrome 10 AR 4
BBS1 209901 Bardet-Biedl syndrome type 1 AR, DiR 14
BBS10 610148 Bardet-Biedl syndrome type 10 AR 11
BBS12 610683 Bardet-Biedl syndrome type 12 AR 8
BBS2 606151 Bardet-Biedl syndrome type 2; retinitis pigmentosa type 74 AR 16
BBS4 600374 Bardet-Biedl syndrome 4 AR 11
BBS5 603650 Bardet-Biedl syndrome 5 AR 27
BBS7 607590 Bardet-Biedl syndrome type 7 AR 17
BBS9 607968 Bardet-Biedl syndrome type 9 AR 24
BCOR 300485 Microphthalmia, syndromic 2 XLD 13
BGN 301870 Meester-Loeys syndrome XL, XLR 2
BIN1 601248 centronuclear myopathy AR 8
BMP1 112264 osteogenesis imperfecta type 13 AR 9
BMP4 112262 orofacial cleft type 11; Microphthalmia, syndromic 6 AD 8
BMPR1B 603248 Brachydactyly type A2; Chondrodysplasia, Acromesomelic, With Genital Anomalies AD, AR 0
BRAF 164757 Cardiofaciocutaneous Syndrome 1; Lung Cancer; Noonan syndrome 7; LEOPARD syndrome 3 AD 20
C8orf37 614477 Cone-rod dystrophy 16; Bardet-Biedl syndrome type 21 AR 3
CANT1 613165 Desbuquois dysplasia type 1 AR 2
CASK 300172 Fg Syndrome 4; Mental retardation and microcephaly with pontine and cerebellar hypoplasia XLD 28
CASR 601199 Hypocalciuric hypercalcemia, type I; Hyperparathyroidism, neonatal; Hypocalcemia, autosomal dominant, with Bartter syndrome; Epilepsy idiopathic generalized, susceptibility to, 8 AD, AR 13
CBL 165360 Leukemia, juvenile myelomonocytic; Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia AD 9
CBS 613381 homocystinuria with or without response to pyridoxine AR 29
CC2D2A 612013 COACH syndrome; Meckel syndrome 6; Joubert syndrome 9 AR 24
CCDC103 614677 Ciliary dyskinesia, primary, 17 AR 3
CCDC114 615038 Ciliary dyskinesia, primary, 20 AR 7
CCDC151 615956 primary Ciliary dyskinesia type 30 AR 0
CCDC28B 610162 Bardet-Biedl syndrome type 1 AR, DiR 1
CCDC39 613798 Ciliary dyskinesia, primary, 14 8
CCDC40 613799 Ciliary dyskinesia, primary, 15 27
CCDC65 611088 Ciliary dyskinesia, primary, 27 AR 1
CCM2 607929 Cerebral Cavernous Malformations type 2 AD 9
CCNO 607752 primary ciliary dyskinesia type 29 AR 3
CDK5RAP2 608201 primary microcephaly 3 AR 14
CDKN1C 600856 Beckwith-Wiedemann syndrome; IMAGE syndrome AD 14
CDON 608707 Holoprosencephaly 11 AD 24
CENPF 600236 Stromme syndrome AR 12
CENPJ 609279 primary microcephaly 6; Seckel syndrome 4 AR 13
CEP135 611423 primary microcephaly 8 AR 16
CEP152 613529 Seckel syndrome 5; primary microcephaly 9 AR 10
CEP164 614848 nephronophthisis 15 AR 14
CEP290 610142 Joubert syndrome type 5; Senior-Loken syndrome type 6; Meckel syndrome type 4; Leber congenital amaurosis type 10; Bardet-Biedl syndrome type 14 AR 51
CEP41 610523 Joubert syndrome 15 AR 3
CEP63 614724 Seckel syndrome 6 AR 22
CFAP298 615494 primary ciliary dyskinesia type 26 AR 1
CFAP53 614759 Heterotaxy, visceral, 6, autosomal recessive AR 0
CFC1 605194 Heterotaxy, visceral, 2, autosomal AD 3
CFL2 601443 nemaline myopathy type 7 AR 11
CHAT 118490 Presynaptic congenital myasthenic syndrome type 6 AR 16
CHD7 608892 CHARGE syndrome; hypogonadotropic hypogonadism-5 with or without anosmia AD 103
CHMP1A 164010 pontocerebellar hypoplasia 8 AR 6
CHRNA1 100690 Multiple pterygium syndrome, lethal type; Myasthenic syndrome, slow-channel congenital; Myasthenic syndrome, fast-channel congenital AD, AR 11
CHRNB1 100710 Myasthenic syndrome, congenital, 2A, slow-channel; Myasthenic syndrome, congenital, 2C, associated with acetylcholine receptor deficiency AD, AR 9
CHRND 100720 Multiple pterygium syndrome, lethal type; slow-channel congenital myasthenic syndrome type 3A; Congenital fast-channel myasthenic syndrome type 3B; ?Myasthenic syndrome, congenital, 3C, associated with acetylcholine receptor deficiency AD, AR 9
CHRNE 100725 slow-channel congenital myasthenic syndrome type 4A; congenital myasthenic syndrome type 4C, associated with acetylcholine receptor deficiency; fast-channel congenital myasthenic syndrome type 4B AD, AR 18
CHRNG 100730 Multiple pterygium syndrome, lethal type; Multiple Pterygium Syndrome, Escobar Variant AR 13
CHST14 608429 Ehlers-Danlos syndrome musculocontractural type 1 AR 5
CHSY1 608183 AR 0
CILK1 612325 AD, AR 0
CLCN5 300008 Dent disease; Hypophosphatemic rickets; Proteinuria, low molecular weight, with hypercalciuric nephrocalcinosis; Nephrolithiasis, type I XLR 1
COASY 609855 Neurodegeneration with brain iron accumulation 6; Pontocerebellar hypoplasia type 12 AR 1
COL10A1 120110 METAPHYSEAL CHONDRODYSPLASIA, SCHMID TYPE AD 5
COL11A1 120280 Marshall syndrome; Fibrochondrogenesis 1; Stickler syndrome 2 AD, AR 48
COL11A2 120290 Stickler syndrome, type III; Otospondylomegaepiphyseal dysplasia; Deafness, autosomal dominant 13; Deafness, autosomal recessive 53; Fibrochondrogenesis 2 AD, AR 38
COL12A1 120320 Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 AD 29
COL1A1 120150 Caffey disease; Ehlers-Danlos syndrome arthrochalasia type 1; osteogenesis imperfecta type 1; osteogenesis imperfecta type 2; osteogenesis imperfecta type 4; OSTEOPOROSIS; osteogenesis imperfecta type 3 AD 63
COL1A2 120160 osteogenesis imperfecta type 2; osteogenesis imperfecta type 4; OSTEOPOROSIS; Ehlers-Danlos syndrome, cardiac valvular form; osteogenesis imperfecta type 3; Ehlers-Danlos syndrome arthrochalasia type 2 AD, AR 52
COL2A1 120140 Epiphyseal dysplasia, multiple, with myopia and deafness; Legg-Calve-Perthes disease; Platyspondylic skeletal dysplasia, Torrance type; Kniest dysplasia; congenital spondyloepiphyseal dysplasia; SMED Strudwick type; Achondrogenesis, type II or hypochondrogenesis; Spondyloperipheral dysplasia; Osteoarthritis with mild chondrodysplasia; Avascular necrosis of the femoral head; Czech dysplasia; Stickler syndrome type 1; Stanescu type spondyloepiphyseal dysplasia AD 38
COL3A1 120180 vascular-type Ehlers-Danlos syndrome AD, AR 31
COL4A1 120130 porencephaly 1; Brain small vessel disease with or without ocular anomalies; Angiopathy, hereditary, with nephropathy, aneurysms, and muscle cramps; Hemorrhage, intracerebral, susceptibility to AD 71
COL5A1 120215 Ehlers-Danlos syndrome classic type 1 AD 91
COL5A2 120190 Ehlers-Danlos syndrome classic type 2 AD 36
COL6A1 120220 Bethlem myopathy type 1; Ullrich congenital muscular dystrophy AD, AR 25
COL6A2 120240 Bethlem myopathy type 1; Ullrich congenital muscular dystrophy AD, AR 31
COL6A3 120250 Bethlem myopathy type 1; Ullrich congenital muscular dystrophy; dystonia 27 AD, AR 35
COL9A1 120210 Stickler syndrome, type IV; Epiphyseal dysplasia, multiple, 6 AD 17
COL9A2 120260 Stickler syndrome, type V AD, AR 12
COL9A3 120270 multiple epiphyseal dysplasia type 3 AD 6
COLQ 603033 congenital myasthenic syndrome type 5 AR 28
COMP 600310 Epiphyseal Dysplasia, Multiple, 1; Pseudoachondroplasia AD 10
COX7B 300885 Linear skin defects with multiple congenital anomalies 2 XLD 0
CPLANE1 614571 oral-facial-digital syndrome 6; Joubert syndrome 17 AR 31
CREB3L1 616215 osteogenesis imperfecta type 16 AR 5
CREBBP 600140 Rubinstein-Taybi syndrome 1 AD 39
CRELD1 607170 Atrioventricular septal defect, partial, with heterotaxy syndrome AD 6
CRIPT 604594 Short stature with microcephaly and distinctive facies AR 0
CRPPA 614631 congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A7; congenital limb-girdle muscular dystrophy-dystroglycanopathy type C7 AR 5
CRTAP 605497 osteogenesis imperfecta type 7 AR 8
CSPP1 611654 Joubert syndrome 21 AR 11
CUL7 609577 3-M syndrome AR 10
CYP1B1 601771 primary congenital glaucoma type 3A; anterior segment dysgenesis type 6, multiple subtypes AR 1
DAG1 128239 congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type C9 AR 6
DCX 300121 type 1 lissencephaly XL 8
DDR2 191311 Spondylometaepiphyseal dysplasia, short limb-hand type AD, AR 3
DHCR24 606418 Desmosterolosis AR 2
DHCR7 602858 Smith-Lemli-Opitz syndrome AR 9
DMP1 600980 Hypophosphatemic Rickets, Autosomal Recessive, 1 AR 1
DNAAF1 613190 Ciliary dyskinesia, primary, 13 AR 9
DNAAF2 612517 Ciliary dyskinesia, primary, 10 6
DNAAF3 614566 Ciliary dyskinesia, primary, 2 AR 2
DNAAF4 608706 Ciliary dyskinesia, primary, 25 AD, AR 0
DNAAF5 614864 Ciliary dyskinesia, primary, 18 AR 12
DNAH11 603339 primary ciliary dyskinesia type 7, with or without situs inversus AR 56
DNAH5 603335 primary ciliary dyskinesia type 3, with or without situs inversus 38
DNAI1 604366 primary ciliary dyskinesia type 1, with or without situs inversus AR 4
DNAI2 605483 primary ciliary dyskinesia type 9, with or without situs inversus 5
DNAL1 610062 Ciliary dyskinesia, primary, 16 AR 2
DNM2 602378 Myopathy, centronuclear 1; CHARCOT-MARIE-TOOTH, DOMINANT INTERMEDIATE TYPE B; Lethal congenital contracture syndrome 5 AD, AR 11
DOK7 610285 congenital myasthenic syndrome type 10 AR 30
DPAGT1 191350 congenital disorder of glycosylation type 1j; Myasthenic syndrome, congenital, with tubular aggregates 13 AR 3
DRC1 615288 primary ciliary dyskinesia, 21 AR 2
DSE 605942 Ehlers-Danlos syndrome musculocontractural type 2 AR 2
DYM 607461 Dyggve-Melchior-Clausen disease AR 5
DYNC1H1 600112 lower extremity-predominant spinal muscular atrophy type 1; type 2O Charcot-Marie-Tooth disease; mental retardation-13 AD 50
DYNC2H1 603297 short-rib thoracic dysplasia-3 with or without polydactyly AR, DiR 10
DYNC2I1 615462 Short-rib thoracic dysplasia 8 with or without polydactyly AR 3
DYNC2I2 613363 Short-rib thoracic dysplasia 11 with or without polydactyly AR 3
DYRK1A 600855 MENTAL RETARDATION, AUTOSOMAL DOMINANT 7 AD 17
EBP 300205 MEND syndrome; Chondrodysplasia punctata, X-linked dominant XLD, XLR 2
ECE1 600423 Hirschsprung disease, cardiac defects, and autonomic dysfunction AD 13
ECEL1 605896 distal arthrogryposis type 5D AR 16
EDN3 131242 congenital central hypoventilation syndrome; Waardenburg syndrome type 4B; Hirschsprung disease 4 AD, AR 8
EDNRB 131244 Waardenburg syndrome type 4A; Hirschsprung disease, susceptibility to, 2; ABCD syndrome AD, AR 6
EFEMP2 604633 Cutis laxa, autosomal recessive, type IB AR 2
EFNB1 300035 Craniofrontonasal dysplasia XLD 8
EFTUD2 603892 Mandibulofacial dysostosis, Guion-Almeida type AD 32
EGR2 129010 Dejerine-Sottas syndrom; congenital hypomyelinating neuropathy; type 1D Charcot-Marie-Tooth disease AD, AR 7
EIF2AK3 604032 Wolcott-Rallison syndrome AR 2
ELN 130160 Cutis laxa, autosomal dominant 1, ADCL1; Supravalvar aortic stenosis AD 6
ENPP1 173335 noninsulin-dependent diabetes mellitus / Diabetes mellitus type II; Arterial calcification, generalized, of infancy, 1; OBESITY; Hypophosphatemic rickets, autosomal recessive, 2; Cole disease AD, AR 8
ERCC1 126380 Cerebrooculofacioskeletal syndrome 4 AR 0
ERCC2 126340 xeroderma pigmentosum complementation group D; photosensitive trichothiodystrophy type 1; cerebrooculofacioskeletal syndrome type 2 AR 8
ERCC5 133530 xeroderma pigmentosum complementation group G; cerebrooculofacioskeletal syndrome type 3 AR 4
ERCC6 609413 Cockayne syndrome, type B; Lung Cancer; Cerebrooculofacioskeletal syndrome 1 AD, AR 12
ERF 611888 Craniosynostosis 4 AD 6
ESCO2 609353 Roberts syndrome AR 12
EVC 604831 Weyers acrofacial dysostosis; Ellis-van Creveld syndrome AD, AR 9
EVC2 607261 Weyers acrofacial dysostosis; Ellis-van Creveld syndrome AD, AR 5
EXOSC3 606489 pontocerebellar hypoplasia type 1B AR 2
FAS 134637 Autoimmune lymphoproliferative syndrome AD 4
FBLN5 604580 Cutis laxa, autosomal recessive, type IA; hereditary neuropathy with or without age-related macular degeneration AD, AR 1
FBN1 134797 Marfan syndrome; stiff skin syndrome; Weill-Marchesani syndrome 2; geleophysic dysplasia 2; Marfan lipodystrophy syndrome AD 76
FBN2 612570 congenital contractural arachnodactyly; early-onset macular degeneration AD 39
FGF23 605380 Hypophosphatemic rickets, autosomal dominant AD, AR 6
FGF8 600483 hypogonadotropic hypogonadism 6 with or without anosmia AD 13
FGFR1 136350 Craniofacial-skeletal-dermatologic dysplasia; Jackson-Weiss syndrome; hypogonadotropic hypogonadism-2 with or without anosmia; Osteoglophonic dysplasia; Hartsfield syndrome AD 24
FGFR2 176943 Apert syndrome; Saethre-Chotzen Syndrome; Craniofacial-skeletal-dermatologic dysplasia; Jackson-Weiss syndrome; Crouzon syndrome; Beare-Stevenson cutis gyrata syndrome; Lacrimoauriculodentodigital Syndrome; Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis; Scaphocephaly, maxillary retrusion, and mental retardation; Gastric Cancer; Bent bone dysplasia syndrome AD 11
FGFR3 134934 Achondroplasia; Bladder Cancer; colorectal cancer; Hypochondroplasia; Lacrimoauriculodentodigital Syndrome; Nevus, Epidermal; Thanatophoric dysplasia, type I; Thanatophoric dysplasia, type II; Spermatocytic seminoma, somatic; Muenke syndrome; Cervical cancer, somatic; CATSHL syndrome; Crouzon syndrome with acanthosis nigricans AD, AR 19
FHL1 300163 Scapuloperoneal myopathy, X-linked dominant; Myopathy, X-linked, with postural muscle atrophy; Emery-Dreifuss muscular dystrophy 6; Myopathy, Reducing Body, X-Linked, Early-Onset, Severe; Myopathy, reducing body, X-linked, childhood-onset XL, XLD, XLR 13
FKBP10 607063 Bruck syndrome 1; osteogenesis imperfecta type 11 AR 8
FKBP14 614505 Ehlers-Danlos syndrome kyphoscoliotic type 2 AR 3
FKRP 606596 Muscular dystrophy-dystroglycanopathy (congenital with or without mental retardation), type B5; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C5; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5 AR 15
FKTN 607440 congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A4; congenital limb-girdle muscular dystrophy-dystroglycanopathy type C4; dilated cardiomyopathy type 1X; congenital muscular dystrophy-dystroglycanopathy without mental retardation type B4 AR 10
FLCN 607273 colorectal cancer; Birt-Hogg-Dube syndrome; Renal carcinoma, chromophobe, somatic; primary spontaneous pneumothorax AD 11
FLNA 300017 Congenital short bowel syndrome; Heterotopia, periventricular / X-linked periventricular heterotopia; Terminal osseous dysplasia; FG syndrome 2; Otopalatodigital syndrome, type II; Frontometaphyseal dysplasia; Melnick-Needles syndrome; otopalatodigital syndrome type I; Cardiac valvular dysplasia, X-linked XL, XLD, XLR 39
FLNB 603381 Atelosteogenesis, type i; Atelosteogenesis, type iii; Boomerang dysplasia; Larsen syndrome; Spondylocarpotarsal synostosis syndrome AD, AR 23
FOXC1 601090 Iridogoniodysgenesis, type 1; Axenfeld-Rieger syndrome, type 3 AD 8
FOXE3 601094 Anterior segment dysgenesis 2, multiple subtypes; Cataract 34, multiple types AD, AR 0
FOXH1 603621 3
FOXL2 605597 Blepharophimosis, epicanthus inversus, and ptosis AD, AR 12
FRAS1 607830 Fraser syndrome AR 10
FREM1 608944 Manitoba oculotrichoanal syndrome; Bifid nose with or without anorectal and renal anomalies; Trigonocephaly 2 AD, AR 6
FREM2 608945 Fraser syndrome type 2 AR 6
GBA 606463 Lewy body dementia; Susceptibility to late-onset Parkinson disease; Gaucher disease type 1; Gaucher disease type 2 (acute); Gaucher disease type 3 (subacute/ chronic); Gaucher disease, cardiovascular form; Gaucher disease, perinatal-lethal form AD, AR 176
GBE1 607839 storage disease type 4; Polyglucosan body disease, adult form AR 40
GDF1 602880 Right atrial isomerism; Transposition of the great arteries, dextro-looped 3 AD, AR 5
GDF3 606522 Klippel-Feil syndrome 3, autosomal dominant; Microphthalmia with coloboma 6; isolated microphthalmia 7 AD 1
GDF5 601146 Brachydactyly type A2; Brachydactyly type C; Grebe type chondrodysplasia; Hunter-Thompson type of acromesomelic dysplasia; Du Pan syndrome; multiple synostoses syndrome type 2; susceptibility to osteoarthritis type 5; brachydactyly type A1; proximal symphalangism type 1B AD, AR 1
GDF6 601147 Klippel-feil syndrome 1, autosomal dominant; isolated microphthalmia 4; Microphthalmia with coloboma 6; Leber congenital amaurosis 17 AD, AR 2
GDNF 600837 pheochromocytoma; congenital central hypoventilation syndrome; Hirschsprung Disease, Susceptibility To, 3 AD 0
GFPT1 138292 congenital myasthenic syndrome with tubular aggregates type 1 AR 7
GJA1 121014 Oculodentodigital dysplasia AD, AR 3
GLE1 603371 Lethal congenital, contracture syndrome 1 AR 2
GLI2 165230 holoprosencephaly 9; Culler-Jones syndrome AD 19
GLI3 165240 Pallister-Hall syndrome; Polydactyly, postaxial, types A1 and B; Preaxial polydactyly type IV; Greig cephalopolysyndactyly syndrome AD 30
GMPPB 615320 Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 14; Muscular dystrophy-dystroglycanopathy (congenital with mental retardation), type B, 14; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 14 AR 2
GNAS 139320 Pseudohypoparathyroidism Ia; Osseous heteroplasia, progressive; McCune-Albright syndrome, somatic, mosaic; ACTH-independent macronodular adrenal hyperplasia; Pseudohypoparathyroidism type Ib; Pseudohypoparathyroidism Ic; Pseudopseudohypoparathyroidism AD 23
GNPAT 602744 rhizomelic chondrodysplasia punctata type 2 AR 6
GORAB 607983 geroderma osteodysplasticum AR 2
GRIP1 604597 AR 2
HCCS 300056 Microphthalmia, syndromic 7 XLD 2
HDAC8 300269 Cornelia de Lange syndrome 5 XLD 6
HESX1 601802 Septooptic dysplasia AD, AR 0
HEXA 606869 Tay-Sachs disease/ GM2-gangliosidosis AR 25
HMGB3 300193 XL 0
HMX1 142992 AR 0
HRAS 190020 Bladder Cancer; Melanocytic nevus syndrome, congenital, somatic; Nevus, Epidermal; Schimmelpenning-Feuerstein-Mims Syndrome; Thyroid Carcinoma, Follicular; Costello syndrome AD 10
HSPG2 142461 Silverman-Handmaker type of dyssegmental dysplasia; Schwartz-Jampel syndrome AR 30
HUWE1 300697 syndromic mental retardation, Turner type XL 29
HYDIN 610812 primary ciliary dyskinesia type 5 AR 131
HYLS1 610693 Hydrolethalus syndrome AR 2
IER3IP1 609382 Microcephaly, epilepsy, and diabetes syndrome AR 1
IFITM5 614757 osteogenesis imperfecta type 5 AD 7
IFT122 606045 Cranioectodermal dysplasia 1 AR 3
IFT140 614620 Mainzer-Saldino syndrome; retinitis pigmentosa type 80 AR 1
IFT172 607386 Short-rib thoracic dysplasia 10 with or without polydactyly AR 4
IFT27 615870 Bardet-Biedl syndrome 19 AR 0
IFT43 614068 Cranioectodermal dysplasia 3 AR 2
IFT80 611177 AR 0
IL11RA 600939 Craniosynostosis and dental anomalies AR 0
INPP5E 613037 Joubert syndrome 1; Mental retardation, truncal obesity, retinal dystrophy, and micropenis AR 18
INPPL1 600829 Opsismodysplasia AR 6
IRF6 607199 van der Woude syndrome; Popliteal pterygium syndrome; susceptibility to orofacial cleft type 6 AD 5
ITGB4 147557 Epidermolysis bullosa simplex, Weber-Cockayne type; junctional epidermolysis bullosa, non-Herlitz type; epidermolysis bullosa with pyloric atresia AD, AR 3
KAT6B 605880 Ohdo syndrome, SBBYS variant; Genitopatellar syndrome AD 20
KATNB1 602703 lissencephaly 6 AR 4
KBTBD13 613727 Nemaline Myopathy 6 AD 4
KDM5C 314690 syndromic mental retardation - Claes-Jensen type XLR 14
KDM6A 300128 Kabuki syndrome 2 XLD 12
KIF11 148760 Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation AD 30
KIF2A 602591 Cortical dysplasia, complex, with other brain malformations 3 AD 4
KIF5C 604593 Cortical dysplasia, complex, with other brain malformations 2 AD 2
KIF7 611254 Acrocallosal syndrome; Joubert syndrome 12; Hydrolethalus syndrome 2 AR 25
KIT 164920 Mast cell disease; Piebaldism; Spermatocytic seminoma, somatic; acute myeloid leukemia; gastrointestinal stromal tumor AD 14
KLHL40 615340 Nemaline myopathy 8, autosomal recessive AR 1
KLHL41 607701 Nemaline myopathy 9 AR 0
KMT2A 159555 Wiedemann-Steiner syndrome AD 37
KMT2D 602113 Kabuki syndrome 1 AD 53
KNL1 609173 primary microcephaly 4 AR 8
KRAS 190070 Arteriovenous malformations of the brain; Bladder Cancer; familial breast-ovarian cancer type 2; Gastric Cancer, Hereditary Diffuse; Schimmelpenning-Feuerstein-Mims Syndrome; Lung Cancer; Pancreatic Cancer; acute myeloid leukemia; Noonan syndrome 3; Autoimmune lymphoproliferative syndrome type IV; Cardiofaciocutaneous syndrome 2 AD 9
KRIT1 604214 Cerebral Cavernous Malformations type 1 AD 6
L1CAM 308840 spastic paraplegia type 1; partial agenesis of the corpus callosum; hydrocephalus with stenosis of the aqueduct of Sylvius XLR 15
LAMA2 156225 congenital muscular dystrophy type 1A; limb-girdle Muscular dystrophy type 23 AR 44
LAMA3 600805 junctional epidermolysis bullosa, non-Herlitz type; junctional epidermolysis bullosa, Herlitz-type; laryngoonychocutaneous syndrome AR 30
LAMB1 150240 lissencephaly 5 AR 6
LAMB3 150310 amelogenesis imperfecta type IA; junctional epidermolysis bullosa, non-Herlitz type; junctional epidermolysis bullosa, Herlitz-type AD, AR 20
LAMC2 150292 junctional epidermolysis bullosa, non-Herlitz type; junctional epidermolysis bullosa, Herlitz-type AR 5
LARGE1 603590 congenital muscular dystrophy-dystroglycanopathy with mental retardation type B6; congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A6 AR 19
LBR 600024 Pelger-Huet anomaly; Greenberg skeletal dysplasia AD, AR 2
LEFTY2 601877 2
LEP 164160 Leptin deficiency AR 3
LEPR 601007 Morbid obesity due to leptin receptor deficiency AR 1
LIFR 151443 Stuve-Wiedemann syndrome AR 14
LMNA 150330 dilated cardiomyopathy-1A; Lipodystrophy, familial partial, 2; Hutchinson-Gilford progeria; limb-girdle muscular dystrophy type 1B; Emery-Dreifuss muscular dystrophy 2; Malouf syndrome; Mandibuloacral dysplasia; Restrictive dermopathy, lethal; type 2B1 Charcot-Marie-Tooth disease; Heart-hand syndrome, Slovenian type; Muscular dystrophy, congenital; Emery-Dreifuss muscular dystrophy 3, AR AD, AR 20
LMOD3 616112 Nemaline myopathy 10 AR 0
LMX1B 602575 Nail-patella syndrome AD 10
LOX 153455 thoracic aortic aneurysm type 10 AD 1
LRP2 600073 Donnai-Barrow syndrome AR 10
LRP5 603506 Hyperostosis Corticalis Generalisata, Benign Form Of Worth, With Torus Palatinus; OSTEOPOROSIS; Osteoporosis-pseudoglioma syndrome; Exudative vitreoretinopathy 4; Bone Mineral Density Quantitative Trait Locus 1; autosomal dominant osteopetrosis type 1; van Buchem disease, type 2 AD, AR 35
LRRC6 614930 Ciliary dyskinesia, primary, 19 AR 2
LZTFL1 606568 Bardet-Biedl syndrome 17 AR 5
LZTR1 600574 Noonan syndrome type 2; SCHWANNOMATOSIS 2; Noonan syndrome 10 AD, AR 19
MAB21L2 604357 Microphthalmia, syndromic 14 AD, AR 1
MAGEL2 605283 Schaaf-Yang syndrome AD 9
MAP2K1 176872 Cardiofaciocutaneous syndrome 3 AD 7
MAP2K2 601263 Cardiofaciocutaneous syndrome 4 AD 8
MASP1 600521 3MC syndrome 1 AR 10
MAT2A 601468 0
MATN3 602109 Epiphyseal dysplasia, multiple, 5 AD, AR 1
MBTPS2 300294 IFAP syndrome with or without BRESHECK syndrome; Keratosis follicularis spinulosa decalvans, X-linked XLR 4
MCPH1 607117 primary microcephaly 1 AR 16
MED12 300188 Opitz-Kaveggia syndrome /FG syndrome-1; Lujan-Fryns syndrome XLR 16
MED17 603810 postnatal progressive microcephaly, seizures, and brain atrophy AR 2
MEGF8 604267 Carpenter syndrome 2 AR 12
MEIS2 601740 Cleft palate, cardiac defects, and mental retardation AD 1
MEOX1 600147 Klippel-Feil syndrome 2 AR 2
MFAP5 601103 AD 0
MFRP 606227 Nanophthalmos 2; isolated microphthalmia 5 AR 0
MFSD2A 614397 Microcephaly 15, primary, autosomal recessive AR 1
MITF 156845 Albinism, Ocular, With Sensorineural Deafness; Tietz Syndrome; Waardenburg syndrome type 2A; Melanoma, Cutaneous Malignant, Susceptibility To, 8 AD, AR 11
MKKS 604896 McKusick-Kaufman syndrome; Bardet-Biedl syndrome type 6 AR 6
MKS1 609883 Meckel syndrome type 1; Bardet-Biedl syndrome type 13; Joubert syndrome type 28 AR 7
MMP13 600108 Metaphyseal dysplasia, Spahr type; Spondyloepimetaphyseal dysplasia, Missouri type AD, AR 9
MMP21 608416 Heterotaxy, visceral, 7, autosomal AR 5
MMP9 120361 Metaphyseal anadysplasia 2 2
MSMO1 607545 Microcephaly, congenital cataract, and psoriasiform dermatitis AR 4
MSX1 142983 Tooth Agenesis, Selective, 1; Witkop Syndrome; Orofacial cleft 5 AD 4
MSX2 123101 Parietal foramina 1; Parietal foramina with cleidocranial dysplasia; Craniosynostosis, type 2 AD 9
MTM1 300415 X-linked myotubular myopathy XLR 6
MUSK 601296 Fetal akinesia deformation sequence; myasthenic syndrome, congenital type 9, associated with acetylcholine receptor deficiency AR 13
MYBPC1 160794 Arthrogryposis, distal, type 1B; Lethal congenital contracture syndrome 4 AD, AR 46
MYCN 164840 Feingold syndrome AD 8
MYH11 160745 familial thoracic aortic aneurysm 4 AD 25
MYH2 160740 Inclusion body myopathy 3, autosomal dominant AD, AR 7
MYH3 160720 distal arthrogryposis type 2A; Distal arthrogryposis type 2B3 (Sheldon-Hall) AD, AR 53
MYH8 160741 distal arthrogryposis type 7; Carney complex variant AD 23
MYLK 600922 Aortic aneurysm, familial thoracic 7 AD, AR 20
MYO18B 607295 Klippel-Feil syndrome 4, autosomal recessive, with myopathy and facial dysmorphism AR 6
MYO7A 276903 Usher syndrome type 1B; deafness type 2; autosomal dominant deafness type 11 AD, AR 31
NAA10 300013 Ogden syndrome; Microphthalmia, syndromic 1 XL, XLD, XLR 1
NALCN 611549 Hypotonia, infantile, with psychomotor retardation and characteristic facies; Congenital contractures of the limbs and face, hypotonia, and developmental delay AD, AR 24
NDE1 609449 lissencephaly 4 AR 3
NDP 300658 Exudative Vitreoretinopathy 2, X-Linked; Norrie disease XLD, XLR 8
NEB 161650 nemaline myopathy type 2 AR 133
NECTIN1 600644 Cleft lip/palate ectodermal dysplasia syndrome AR 2
NEK1 604588 Short-rib thoracic dysplasia 6 with or without polydactyly AD, AR, DiR 2
NEK8 609799 nephronophthisis 9; Renal-hepatic-pancreatic dysplasia 2 AR 2
NF1 613113 neurofibromatosis type 1; Neurofibromatosis-Noonan syndrome; Leukemia, juvenile myelomonocytic AD 140
NF2 607379 neurofibromatosis type 2; Schwannomatosis; Meningioma, familial, susceptibility to AD 16
NHEJ1 611290 Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation 9
NIPBL 608667 Cornelia de Lange syndrome 1 AD 40
NKX2-5 600584 Atrial Septal Defect 7 With Or Without Atrioventricular Conduction Defects; Tetralogy of Fallot; Conotruncal Heart Malformations; Hypothyroidism, Congenital, Nongoitrous, 5; Ventricular septal defect 3; Hypoplastic left heart syndrome 2 AD 3
NKX3-2 602183 Spondylo-megaepiphyseal-metaphyseal dysplasia AR 0
NME8 607421 Ciliary dyskinesia, primary, 6 AR 10
NODAL 601265 Heterotaxy, visceral, 5, autosomal AD 2
NOG 602991 proximal symphalangism 1A AD 0
NOTCH1 190198 aortic valve disease type 1; Adams-Oliver syndrome 5 AD 12
NPHP1 607100 nephronophthisis 1; Joubert syndrome 4 AR 19
NPHP3 608002 Renal-hepatic-pancreatic dysplasia 1; Meckel syndrome 7; nephronophthisis 3 AR 16
NR0B2 604630 OBESITY AD, AR 0
NRAS 164790 colorectal cancer; Melanocytic nevus syndrome, congenital, somatic; Nevus, Epidermal; Schimmelpenning-Feuerstein-Mims Syndrome; Thyroid Carcinoma, Follicular; Neurocutaneous melanosis, somatic; Noonan syndrome 6; Autoimmune lymphoproliferative syndrome type IV AD 5
NRG1 142445 10
NSDHL 300275 CK syndrome; CHILD syndrome XLD, XLR 4
OCRL 300535 Dent disease type 2; Lowe oculocerebrorenal syndrome XLR 13
OFD1 300170 Simpson-Golabi-Behmel syndrome type 2; Retinitis pigmentosa 23; Joubert syndrome 10; oral-facial-digital syndrome 1 XLD, XLR 22
ORC1 601902 Meier-gorlin syndrome 1 AR 0
OTX2 600037 Microphthalmia, syndromic 5; Pituitary hormone deficiency, combined, 6 AD 2
P3H1 610339 osteogenesis imperfecta type 8 AR 5
PAFAH1B1 601545 lissencephaly type 1 AD 20
PAX2 167409 Papillorenal syndrome AD 5
PAX3 606597 Waardenburg syndrome, type 3; Waardenburg syndrome type 1 AD, AR 13
PAX6 607108 Aniridia 1; foveal hypoplasia type 1 AD 17
PCNT 605925 microcephalic osteodysplastic primordial dwarfism type 2 AR 42
PDCD10 609118 Cerebral cavernous malformations 3 2
PDE6D 602676 Joubert syndrome 22 AR 1
PEX7 601757 Rhizomelic chondrodysplasia punctata type 1; peroxisome biogenesis disorder type 9B (Zellweger) AR 15
PHC1 602978 primary microcephaly 11 AR 4
PHEX 300550 X-linked dominant hypophosphatemic rickets XLD 14
PHF6 300414 Borjeson-Forssman-Lehmann syndrome XLR 5
PIEZO2 613629 Arthrogryposis, distal, type 5; Marden-Walker syndrome; Arthrogryposis, distal, with impaired proprioception and touch AD, AR 55
PIGV 610274 Hyperphosphatasia with mental retardation syndrome type 1 AR 2
PITX2 601542 Axenfeld-Rieger syndrome, type 1 AD 4
PKD1L1 609721 Visceral heterotaxy type 8 AR 1
PKD2 173910 polycystic kidney disease type 2 AD 44
PKHD1 606702 polycystic kidney disease type 4 with or without polycystic liver disease AR 112
PLK4 605031 autosomal recessive microcephaly and chorioretinopathy, 2 AR 1
PLOD1 153454 Ehlers-Danlos syndrome kyphoscoliotic type 1 AR 22
PLOD2 601865 Bruck syndrome 2 AR 11
PMM2 601785 congenital disorder of glycosylation type 1a AR 3
PNKP 605610 type 2B2 Charcot-Marie-Tooth disease; early infantile epileptic encephalopathy 10 AR 28
PNPLA6 603197 Boucher-Neuhauser syndrome; spastic paraplegia 39 AR 55
POMC 176830 OBESITY; Proopiomelanocortin Deficiency AD, AR 2
POMGNT1 606822 congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A3; congenital muscular dystrophy-dystroglycanopathy with mental retardation type B3; congenital limb-girdle muscular dystrophy-dystroglycanopathy type C3; retinitis pigmentosa type 76 AR 19
POMGNT2 614828 congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A8 AR 5
POMK 615247 congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies A12; congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type C12 AR 5
POMT1 607423 congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A1; congenital limb-girdle muscular dystrophy-dystroglycanopathy type C1; congenital muscular dystrophy-dystroglycanopathy with mental retardation type B1 AR 25
POMT2 607439 congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies type A2; congenital muscular dystrophy-dystroglycanopathy with mental retardation type B2; congenital limb-girdle muscular dystrophy-dystroglycanopathy type C2 AR 18
POR 124015 Antley-Bixler syndrome with genital anomalies and disordered steroidogenesis; Disordered Steroidogenesis Due To Cytochrome P450 Oxidoreductase Deficiency AR 11
PPARG 601487 noninsulin-dependent diabetes mellitus / Diabetes mellitus type II; OBESITY; Lipodystrophy, familial partial, type 3 AD, AR 2
PPIB 123841 osteogenesis imperfecta type 9 AR 2
PQBP1 300463 Renpenning Syndrome 1 XLR 2
PRDM5 614161 Brittle Cornea Syndrome 2 AR 2
PRKAR1A 188830 Acrodysostosis 1 With Or Without Hormone Resistance; Carney complex, type 1; Myxoma, intracardiac; Pigmented nodular adrenocortical disease, primary, 1 AD 14
PRKG1 176894 familial thoracic aortic aneurysm type 8 AD 1
PROM1 604365 Stargardt disease 4; Macular dystrophy, retinal, 2; Retinitis pigmentosa 41; Cone-rod dystrophy 12 AD, AR 27
PRPH2 179605 Retinitis punctata albescens; Patterned dystrophy of retinal pigment epithelium (macular dystrophy); Retinitis pigmentosa 7; vitelliform macular dystrophy-3; Choriodal dystrophy, central areolar 2 AD, AR 7
PRSS56 613858 isolated microphthalmia 6 AR 0
PTCH1 601309 Gorlin syndrome; Holoprosencephaly-7 AD 49
PTH1R 168468 primary failure of tooth eruption; Metaphyseal chondrodysplasia, Murk Jansen type; Chondrodysplasia, Blomstrand type; Eiken syndrome AD, AR 5
PTPN11 176876 LEOPARD syndrome 1; Noonan syndrome 1; Leukemia, juvenile myelomonocytic AD 13
PYCR1 179035 autosomal recessive cutis laxa type 2B AR 3
PYCR2 616406 hypomyelinating leukodystrophy-10 AR 3
QARS1 603727 Microcephaly, progressive, seizures, and cerebral and cerebellar atrophy AR 2
RAB18 602207 Warburg micro syndrome 3 AR 6
RAB23 606144 Carpenter syndrome AR 0
RAB3GAP1 602536 Warburg micro syndrome 1 AR 12
RAB3GAP2 609275 Martsolf syndrome; Warburg micro syndrome 2 AR 7
RAD21 606462 Cornelia de Lange syndrome type 4 AD, AR 12
RAF1 164760 Noonan syndrome 5; Cardiomyopathy, dilated, 1NN AD 8
RAPSN 601592 congenital myasthenic syndrome, type 11, associated with acetylcholine receptor deficiency AR 13
RARB 180220 syndromic microphthalmia, type 12 AD, AR 2
RARS2 611524 pontocerebellar hypoplasia type 6 AR 15
RASA1 139150 Capillary malformation-arteriovenous malformation AD 2
RASA2 601589 4
RAX 601881 isolated microphthalmia 3 AR 1
RBBP8 604124 Jawad syndrome / Microcephaly with mental retardation and digital anomalies; Seckel syndrome 2 AR 8
RBP4 180250 Retinal dystrophy, iris coloboma, and comedogenic acne syndrome AD, AR 1
RDH5 601617 Retinitis punctata albescens AD, AR 1
RELN 600514 lissencephaly 2; familial temporal lobe epilepsy, 7 AD, AR 46
RET 164761 Hirschsprung disease; familial medullary thyroid carcinoma; multiple endocrine neoplasia 2B; pheochromocytoma; multiple endocrine neoplasia 2A; congenital central hypoventilation syndrome AD 17
RHO 180380 Retinitis punctata albescens; Night blindness, congenital stationary, autosomal dominant 1; Retinitis Pigmentosa 4 AD, AR 1
RIN2 610222 MACS syndrome AR 1
RIT1 609591 Noonan syndrome 8 AD 2
RLBP1 180090 Retinitis punctata albescens AD, AR 4
ROR2 602337 Brachydactyly, type B1; Robinow syndrome, autosomal recessive AD, AR 3
RPGRIP1L 610937 COACH syndrome; Joubert syndrome 7; Meckel syndrome type 5 AR 18
RPL10 312173 Autism, susceptibility to, X-linked 5 XLR 1
RPS6KA3 300075 MENTAL RETARDATION, X-LINKED 19; Coffin-Lowry syndrome XLD 17
RSPH1 609314 primary ciliary dyskinesia, 24 AR 0
RSPH4A 612647 Ciliary dyskinesia, primary, 11 5
RSPH9 612648 Ciliary dyskinesia, primary, 12 2
RUNX2 600211 Cleidocranial dysplasia AD 11
RXYLT1 605862 congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies A10 AR 2
RYR1 180901 central core disease; malignant hyperthermia; minicore myopathy with external ophthalmoplegia AD, AR 154
SALL1 602218 Townes-Brocks syndrome AD 30
SALL2 602219 AR 0
SALL4 607343 Okihiro syndrome AD 15
SASS6 609321 autosomal recessive primary microcephaly, 14 AR 1
SATB2 608148 SATB2-associated syndrome (SAS) :Glass syndrome AD 8
SBDS 607444 Shwachman-Bodian-Diamond syndrome; Aplastic Anemia AR 11
SCN4A 603967 Paramyotonia congenita; Hyperkalemic periodic paralysis, type 2; Atypical myotonia congenita, acetazolamide-responsive; Hypokalemic periodic paralysis, type 2; Myasthenic syndrome, acetazolamide-responsive AD, AR 21
SDCCAG8 613524 Senior-Loken syndrome 7; Bardet-Biedl syndrome 16 AR 12
SELENON 606210 Myopathy, congenital, with fiber-type disproportion; rigid spine syndrome AD, AR 22
SEPSECS 613009 pontocerebellar hypoplasia type 2D AR 5
SERPINF1 172860 osteogenesis imperfecta type 6 AR 2
SERPINH1 600943 Preterm premature rupture of the membranes, susceptibility to; osteogenesis imperfecta type 10 AR 3
SHH 600725 Holoprosencephaly 3; Solitary Median Maxillary Central Incisor; Schizencephaly; Microphthalmia, Isolated, With Coloboma 5 AD 5
SHOC2 602775 Noonan Syndrome-Like Disorder With Loose Anagen Hair AD 6
SHROOM4 300579 Stocco dos Santos X-linked mental retardation syndrome XL 9
SIX3 603714 Holoprosencephaly 2; Schizencephaly AD 9
SIX6 606326 Microphthalmia with cataract 2 AR 1
SKI 164780 Shprintzen-Goldberg Craniosynostosis Syndrome AD 3
SLC25A19 606521 Microcephaly, Amish type; Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type) AR 6
SLC26A2 606718 Diastrophic dysplasia; multiple epiphyseal dysplasia type 4; Atelosteogenesis type II; Achondrogenesis type IB AR 6
SLC2A10 606145 arterial tortuosity syndrome AR 9
SLC34A3 609826 Hypophosphatemic rickets with hypercalciuria AR 6
SLC35D1 610804 Schneckenbecken dysplasia AR 1
SLC39A13 608735 Ehlers-Danlos syndrome spondylodysplastic type 3 AR 2
SLC5A7 608761 Neuronopathy, distal hereditary motor, type VIIA; Myasthenic syndrome, congenital, 20, presynaptic AD, AR 1
SLC9A6 300231 Christianson type of X-linked syndromic mental retardation XLD 14
SMAD2 601366 2
SMAD3 603109 Loeys-Dietz syndrome 3 AD 6
SMAD4 600993 Myhre syndrome; Juvenile polyposis syndrome, infantile form; Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome; Pancreatic Cancer AD 3
SMAD6 602931 Aortic valve disease 2; Craniosynostosis type 7 AD 4
SMARCA2 600014 Nicolaides-Baraitser syndrome AD 15
SMARCA4 603254 Rhabdoid tumor predisposition syndrome 2; mental retardation-16 AD 17
SMARCB1 601607 Schwannomatosis; Rhabdoid tumors, somatic; Coffin-Siris syndrome 3 AD 10
SMARCE1 603111 Meningioma, familial, susceptibility to AD 4
SMC1A 300040 Cornelia de Lange syndrome 2 XLD 12
SMC3 606062 Cornelia de Lange syndrome 3 AD 24
SMCHD1 614982 Fascioscapulohumeral muscular dystrophy 2, digenic AD 3
SMOC1 608488 AR 0
SNAI2 602150 Piebaldism; Waardenburg syndrome type 2d AD, AR 0
SOS1 182530 Noonan syndrome 4 AD 18
SOS2 601247 Noonan syndrome type 9 AD 4
SOX10 602229 PCWH syndrome; Waardenburg syndrome type 2E; Waardenburg syndrome, type 4C AD 20
SOX2 184429 Microphthalmia, Syndromic 3 AD 8
SOX9 608160 campomelic dysplasia AD 14
SP7 606633 osteogenesis imperfecta type 12 AR 2
SPAG1 603395 Primary Ciliary dyskinesia type 28 AR 0
SPRED1 609291 Legius syndrome AD 15
STAMBP 606247 Microcephaly-capillary malformation syndrome AR 1
STIL 181590 primary microcephaly 7 AR 5
STRA6 610745 Microphthalmia, isolated, with coloboma 8 AR 12
SUMO1 601912 0
TAF6 602955 Alazami-Yuan syndrome AR 6
TBC1D20 611663 Warburg micro syndrome 4 AR 1
TBC1D24 613577 DOOR syndrome; Myoclonic epilepsy, infantile, familial; Rolandic epilepsy with proxysmal exercise-induced dystonia and writer's cramp; deafness type 86; Epileptic encephalopathy, early infantile, 16; deafness type 65 AD, AR 7
TBX5 601620 Holt-Oram syndrome AD 17
TCF12 600480 Craniosynostosis 3 AD 4
TCF4 602272 Pitt-Hopkins syndrome AD 33
TCTN1 609863 Joubert syndrome 13 AR 5
TCTN2 613846 Meckel syndrome 8; Joubert syndrome type 24 AR 19
TCTN3 613847 oral-facial-digital syndrome 4; Joubert syndrome 18 AR 2
TENM3 610083 microphthalmia with coloboma 9 AR 23
TFAP2A 107580 Branchiooculofacial syndrome AD 5
TGFB2 190220 Loeys-Dietz syndrome 4 AD 5
TGFB3 190230 Arrhythmogenic right ventricular dysplasia 1; Loeys-Dietz syndrome 5 AD 12
TGFBR1 190181 Multiple Self-Healing Squamous Epithelioma, Susceptibility To; Loeys-Dietz syndrome 1 AD 8
TGFBR2 190182 Esophageal cancer, somatic; Loeys-Dietz syndrome 2; Colorectal cancer, hereditary nonpolyposis, type 6 AD 5
TGIF1 602630 Holoprosencephaly-4 AD 12
TK2 188250 mitochondrial DNA depletion syndrome 2 AR 7
TMEM138 614459 Joubert syndrome 16 AR 1
TMEM216 613277 Meckel Syndrome type 2; Joubert syndrome type 2 AR 0
TMEM231 614949 Joubert syndrome 20; Meckel syndrome, type 11 AR 10
TMEM237 614423 Joubert syndrome 14 AR 12
TMEM67 609884 COACH syndrome; Meckel Syndrome, Type 3; Joubert syndrome 6; nephronophthisis 11; Bardet-Biedl syndrome type 14 AR 22
TNFRSF11B 602643 Paget disease of bone 5, juvenile-onset AR 1
TNNI2 191043 distal arthrogryposis type 2B AD 10
TNNT1 191041 Nemaline myopathy 5, Amish type AR 6
TNNT3 600692 AD 20
TNXB 600985 classic-like Ehlers-Danlos syndrome; Vesicoureteral reflux type 8 AD, AR 83
TOR1A 605204 dystonia 1 AD 19
TP63 603273 ADULT syndrome; Hay-Wells syndrome; Rapp-Hodgkin syndrome; Limb-mammary syndrome; Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3; Split-hand/foot malformation 4 AD 7
TPM2 190990 Nemaline myopathy type 4, autosomal dominant AD 12
TPM3 191030 Myopathy, congenital, with fiber-type disproportion; Nemaline myopathy 1, autosomal dominant or recessive AD, AR 11
TRIM32 602290 limb-girdle muscular dystrophy type 2H; Bardet-Biedl syndrome 11 AR 2
TRIP11 604505 Achondrogenesis, type IA AR 10
TRMT10A 616013 Microcephaly, short stature, and impaired glucose metabolism 1 AR 1
TRPS1 604386 trichorhinophalangeal syndrome 1 AD 15
TRPV4 605427 Brachyolmia type 3; Metatropic dysplasia; Spondylometaphyseal dysplasia, Kozlowski type; Hereditary motor and sensory neuropathy, type IIc AD 13
TSC1 605284 tuberous sclerosis type 1 AD 68
TSC2 191092 tuberous sclerosis-2 AD 150
TSEN2 608753 pontocerebellar hypoplasia type 2B AR 7
TSEN54 608755 pontocerebellar hypoplasia type 4; pontocerebellar hypoplasia type 2A; pontocerebellar hypoplasia type 5 AR 12
TTC21B 612014 Short-rib thoracic dysplasia 4 with or without polydactyly; nephronophthisis 12 AD, AR 24
TTC8 608132 retinitis pigmentosa type 51; Bardet-Biedl syndrome type 8 AR 13
TUBA1A 602529 lissencephaly 3 AD 11
TUBA8 605742 Polymicrogyria with optic nerve hypoplasia AR 1
TUBB 191130 Cortical dysplasia, complex, with other brain malformations 6 AD 3
TUBB2A 615101 Cortical dysplasia, complex, with other brain malformations 5 AD 4
TUBB2B 612850 Polymicrogyria, symmetric or asymmetric AD 5
TUBB3 602661 Fibrosis of extraocular muscles, congenital, 3A; Cortical dysplasia, complex, with other brain malformations AD 3
TUBG1 191135 Cortical dysplasia, complex, with other brain malformations 4 AD 0
TUBGCP4 609610 AR 0
TUBGCP6 610053 Microcephaly and chorioretinopathy with or without mental retardation AR 32
TWIST1 601622 Saethre-Chotzen Syndrome; Craniosynostosis 1; Robinow-Sorauf syndrome AD 4
TYR 606933 Albinism, Ocular, With Sensorineural Deafness; oculocutaneous albinism type 1A; Skin/hair/eye pigmentation 3; Albinism, oculocutaneous, type IB AD, AR 21
UBA1 314370 X-linked infantile spinal muscular atrophy type 2 XLR 2
VAMP1 185880 Spastic ataxia 1, autosomal dominant; Myasthenic syndrome, congenital, 25 AD, AR 15
VIPAS39 613401 Arthrogryposis, renal dysfunction, and cholestasis 2 AR 2
VLDLR 192977 Cerebellar ataxia, mental retardation, and dysequilibrium syndrome AR 16
VPS13B 607817 Cohen syndrome AR 28
VPS53 615850 pontocerebellar hypoplasia type 2E AR 1
VRK1 602168 pontocerebellar hypoplasia type 1A AR 5
VSX2 142993 microphthalmia with coloboma 3; isolated microphthalmia 2 6
WDPCP 613580 Bardet-Biedl syndrome 15 AR 9
WDR19 608151 Short-rib thoracic dysplasia 5 with or without polydactyly; nephronophthisis 13; Cranioectodermal dysplasia 4; Senior-Loken syndrome 8 AR 1
WDR35 613602 Cranioectodermal dysplasia 2 AR 2
WDR62 613583 primary microcephaly 2 AR 19
WNT1 164820 osteogenesis imperfecta type 15; susceptibility to early-onset autosomal dominant osteoporosis AR 3
WNT5A 164975 Robinow syndrome, autosomal dominant AD 4
WNT7A 601570 Fuhrmann syndrome; Ulna and fibula, absence of, with sever limb deficiency AR 8
YWHAE 605066 9
ZEB2 605802 Mowat-Wilson syndrome AD 47
ZIC2 603073 Holoprosencephaly 5 AD 17
ZIC3 300265 Heterotaxy, visceral, 1, x-linked; Vacterl association, x-linked, with or without hydrocephalus XLR 1
ZMYND10 607070 primary ciliary dyskinesia, 22 AR 1
ZNF335 610827 primary microcephaly 10 AR 4
ZNF423 604557 nephronophthisis 14; Joubert syndrome 19 AD, AR 10
ZNF469 612078 Brittle cornea syndrome AR 10


Differential diagnosis

The differential diagnosis of Noonan - CFC syndrome-related disorders – depending on the major symptoms in the initial case – includes the following diseases:

  • Other RASopathies including Costello syndrome, Craniofaciocutaneous syndrome, LEOPARD syndrome, Neurofibromatosis type 1, SPRED1 spectrum
  • Chromosomal abnormalities including X-/XY mosaicism, Turner syndrome
  • Fetal hydantoin syndrome
  • Other syndromes with developmental delay, short stature and cardiac defects (with other overlapping symptoms): Williams syndrome, Aarskog syndrome, in utero alcohol/primidone intoxication, and others

Testing strategy

To confirm/establish the diagnosis, we offer Noonan - CFC syndrome panel sequencing and deletion/duplication gene testing. We also offer a broad selection of NGS panels that are designed for the molecular diagnostics of related conditions/phenotypes. Thus, CENTOGENE offers the following testing strategy for Noonan - CFC syndrome panel gene testing:

Step 1: Noonan - CFC syndrome panel sequencing – covers the entire coding region, exon/intron boundaries and 200 bp of the gene promoter for all the genes included in the Noonan - CFC syndrome panel.

Step 2: Deletion/duplication analysis/mutational scanning of selected Noonan - CFC syndrome panel genes (NF1, SPRED1).

Step 3: If no mutation is identified after analysis with the Noonan - CFC syndrome panel, we can offer whole exome sequencing, based on NGS technology.


Referral reasons

The following patients should be tested using CENTOGENE´s Noonan - CFC syndrome panel:

  • Newborns affected with characteristic NS-facial features, short stature, congenital heart defects, etc. and with a positive family history for NS-symptoms
  • Newborns/infants without a positive family history for NS, but with specific clinical findings
  • Genetic testing (using CENTOGENE´s Noonan syndrome panel) is useful to confirm the diagnosis and identify the disease causing mutations within a family, regardless of intensity of clinical features, in order to allow for carrier testing and prenatal diagnosis.

Test utility

Sequencing, deletion/duplication of this gene and related genes should be performed in all individuals suspected of having Noonan syndrome and suspected phenotypes. In parallel, other genes reported to be related with this clinical phenotype should also be analyzed for the presence of mutations, due to the overlap in many clinical features caused by those particular genes.

Confirmation of a clinical diagnosis through genetic testing can allow for genetic counseling and may direct medical management. Genetic counseling can provide a patient and/or family with the natural history of the Noonan syndrome and related disorders, identify at-risk family members, provide reproductive risks as well as preconception/prenatal options, and allow for appropriate referral for patient support and/or resources.