ORPHA:648

Noonan syndrome

Type: Malformation syndrome
Group: Disorder
Inheritance: Autosomal dominant, Autosomal recessive
Age of onset: Antenatal, Childhood, Infancy, Neonatal
Status: active

A rare, highly variable, multisystemic disorder mainly characterized by short stature, distinctive facial features, congenital heart defects, cardiomyopathy and an increased risk to develop tumors in childhood.

Names in Orphadata languages

12 of 12 languages

Lang	Name	Synonyms
en	Noonan syndrome
fr	Syndrome de Noonan
de	Noonan-Syndrom
es	Síndrome de Noonan
it	Sindrome di Noonan
nl	Syndroom van Noonan
pt	Síndrome Noonan	Síndrome pseudo-Turner
pl	Zespół Noonan
cs	Syndrom Noonanové
uk	Синдром Нунана
zh	Noonan综合征
tr	Noonan sendromu

Definition in:

Cross-references

qualifier = Orphanet mapping relation

Source	Code	Qualifier	ICD relation	Validation
OMIM	163950	E		validated
OMIM	605275	BTNT		validated
OMIM	609942	BTNT		validated
OMIM	610733	BTNT		validated
OMIM	611553	BTNT		validated
OMIM	613224	BTNT		validated
OMIM	613706	BTNT		validated
OMIM	615355	BTNT		validated
OMIM	616559	BTNT		validated
OMIM	616564	BTNT		validated
OMIM	618499	BTNT		validated
OMIM	618624	BTNT		validated
OMIM	619087	BTNT		validated
OMIM	619745	BTNT		validated
ICD-10	Q87.1	NTBT	inclusion	validated
ICD-11	LD2F.15	E	specific	validated
MONDO	0018997	E		validated
MeSH	D009634	E		validated
UMLS	C0028326	E		validated
GARD	10955	E		validated
MedDRA	10029748	E		validated

E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.

Classification

Preferential parent (Orphanet linearisation):

ORPHA:93890Rare developmental defect during embryogenesis

Parents in the classifications (13):

ORPHA:568047Disorder with multisystemic involvement and primary lymphedema
rare developmental anomalies during embryogenesis; rare genetic diseases; rare skin diseases; rare circulatory system diseases
ORPHA:611327Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare genetic diseases
ORPHA:619340Inherited hematologic cancer-predisposing syndrome
rare genetic diseases; rare neoplastic diseases
ORPHA:102283Multiple congenital anomalies/dysmorphic syndrome-intellectual disability
rare developmental anomalies during embryogenesis; rare neurological diseases
ORPHA:98733Noonan syndrome and Noonan-related syndrome
rare developmental anomalies during embryogenesis; rare cardiac malformations; rare genetic diseases
ORPHA:183422Polymalformative genetic syndrome with increased risk of developing cancer
rare genetic diseases; rare neoplastic diseases
ORPHA:477771Rare disorder with a moyamoya angiopathy
rare genetic diseases; rare neurological diseases
ORPHA:181441Rare disorder with hypergonadotropic hypogonadism
rare genetic diseases; rare endocrine diseases; rare infertility disorders
ORPHA:98578Rare disorder with ptosis
rare developmental anomalies during embryogenesis; rare genetic diseases; rare ophthalmic disorders
ORPHA:217595Syndrome associated with hypertrophic cardiomyopathy
rare cardiac diseases; rare genetic diseases; rare transplant-related disorders
ORPHA:139393Syndromic craniosynostosis
rare developmental anomalies during embryogenesis; rare genetic diseases; rare bone diseases
ORPHA:98576Syndromic outer canthal malposition
rare developmental anomalies during embryogenesis; rare genetic diseases; rare ophthalmic disorders
ORPHA:93547Syndromic renal or urinary tract malformation
rare developmental anomalies during embryogenesis; rare genetic diseases; rare renal diseases; rare transplant-related disorders

No children.

Genes

15 direct

Gene	Association	Status	HGNC	Ensembl	OMIM	Locus	Name	Source of validation
RRAS	Candidate gene tested in	Not yet assessed	HGNC:10447	ENSG00000126458	165090	19q13.33	RAS related	24705357[PMID]
RAF1	Disease-causing germline mutation(s) (gain of function) in	Assessed	HGNC:9829	ENSG00000132155	164760	3p25.2	Raf-1 proto-oncogene, serine/threonine kinase	17603483[PMID]
RIT1	Disease-causing germline mutation(s) (gain of function) in	Assessed	HGNC:10023	ENSG00000143622	609591	1q22	Ras like without CAAX 1	23791108[PMID]
SOS1	Disease-causing germline mutation(s) (gain of function) in	Assessed	HGNC:11187	ENSG00000115904	182530	2p22.1	SOS Ras/Rac guanine nucleotide exchange factor 1	17143285[PMID]
RASA2	Disease-causing germline mutation(s) (loss of function) in	Assessed	HGNC:9872	ENSG00000155903	601589	3q23	RAS p21 protein activator 2	25049390[PMID]
BRAF	Disease-causing germline mutation(s) in	Assessed	HGNC:1097	ENSG00000157764	164757	7q34	B-Raf proto-oncogene, serine/threonine kinase	19206169[PMID]
CBL	Disease-causing germline mutation(s) in	Assessed	HGNC:1541	ENSG00000110395	165360	11q23.3	Cbl proto-oncogene	25952305[PMID]
KRAS	Disease-causing germline mutation(s) in	Assessed	HGNC:6407	ENSG00000133703	190070	12p12.1	KRAS proto-oncogene, GTPase	16773572[PMID]
LZTR1	Disease-causing germline mutation(s) in	Assessed	HGNC:6742	ENSG00000099949	600574	22q11.21	leucine zipper like post translational regulator 1	25795793[PMID]
MRAS	Disease-causing germline mutation(s) in	Assessed	HGNC:7227	ENSG00000158186	608435	3q22.3	muscle RAS oncogene homolog	28289718[PMID]
NRAS	Disease-causing germline mutation(s) in	Assessed	HGNC:7989	ENSG00000213281	164790	1p13.2	NRAS proto-oncogene, GTPase	19966803[PMID]
PTPN11	Disease-causing germline mutation(s) in	Assessed	HGNC:9644	ENSG00000179295	176876	12q24.13	protein tyrosine phosphatase non-receptor type 11	19760651[PMID]
RRAS2	Disease-causing germline mutation(s) in	Assessed	HGNC:17271	ENSG00000133818	600098	11p15.2	RAS related 2	31130285[PMID]
SOS2	Disease-causing germline mutation(s) in	Assessed	HGNC:11188	ENSG00000100485	601247	14q21.3	SOS Ras/Rho guanine nucleotide exchange factor 2	25795793[PMID]
SPRED2	Disease-causing germline mutation(s) in	Assessed	HGNC:17722	ENSG00000198369	609292	2p14	sprouty related EVH1 domain containing 2	34626534[PMID]

Prevalence and incidence

2 records

Type	Class	Value	Area	Qualification	Validation	Source
Prevalence at birth	6-9 / 10 000	70 / 100 000	United States	Value and class	Validated	3895929[PMID]_ORPHANET
Point prevalence	1-5 / 10 000	—	Worldwide	Class only	Validated	European Reference Network on Rare Congenital Malformations and Rare Intellectual Disability[OTHER]

Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.

HPO phenotypes

70 annotations · validated 2023-07-21

HPO	Term (as annotated by Orphanet)	Diagnostic
Very frequent (99-80%)
HP:0003115	Abnormal EKG
HP:0030680	Abnormal cardiovascular system morphology
HP:0002167	Abnormality of speech or vocalization
HP:0010318	Aplasia/Hypoplasia of the abdominal wall musculature
HP:0000476	Cystic hygroma
HP:0000494	Downslanted palpebral fissures
HP:0001260	Dysarthria
HP:0100625	Enlarged thorax
HP:0000348	High forehead
HP:0000218	High palate
HP:0000316	Hypertelorism
HP:0000044	Hypogonadotropic hypogonadism
HP:0001382	Joint hypermobility
HP:0000347	Micrognathia
HP:0011800	Midface retrusion
HP:0001324	Muscle weakness
HP:0000768	Pectus carinatum
HP:0000767	Pectus excavatum
HP:0000358	Posteriorly rotated ears
HP:0000520	Proptosis
HP:0000508	Ptosis
HP:0004415	Pulmonary artery stenosis
HP:0004322	Short stature
HP:0000179	Thick lower lip vermilion
HP:0000391	Thickened helices
HP:0000474	Thickened nuchal skin fold
HP:0000325	Triangular face
HP:0000465	Webbed neck
HP:0006610	Wide intermamillary distance
Frequent (79-30%)
HP:0001892	Abnormal bleeding
HP:0007477	Abnormal dermatoglyphics
HP:0011362	Abnormal hair quantity
HP:0011869	Abnormal platelet function
HP:0001641	Abnormal pulmonary valve morphology
HP:0001928	Abnormality of coagulation
HP:0000078	Abnormality of the genital system
HP:0100763	Abnormality of the lymphatic system
HP:0001743	Abnormality of the spleen
HP:0011675	Arrhythmia
HP:0000635	Blue irides
HP:0002208	Coarse hair
HP:0000028	Cryptorchidism
HP:0002750	Delayed skeletal maturation
HP:0008872	Feeding difficulties in infancy
HP:0002240	Hepatomegaly
HP:0001252	Hypotonia
HP:0002162	Low posterior hairline
HP:0012758	Neurodevelopmental delay
HP:0002650	Scoliosis
HP:0000486	Strabismus
Occasional (29-5%)
HP:0011381	Aplasia of the semicircular canal
HP:0001631	Atrial septal defect
HP:0001156	Brachydactyly
HP:0000978	Bruising susceptibility
HP:0004209	Clinodactyly of the 5th finger
HP:0001680	Coarctation of aorta
HP:0012569	Delayed menarche
HP:0010946	Dilatation of the renal pelvis
HP:0001639	Hypertrophic cardiomyopathy
HP:0001249	Intellectual disability
HP:0012209	Juvenile myelomonocytic leukemia
HP:0001004	Lymphedema
HP:0000995	Melanocytic nevus
HP:0000639	Nystagmus
HP:0000938	Osteopenia
HP:0008897	Postnatal growth retardation
HP:0002974	Radioulnar synostosis
HP:0000407	Sensorineural hearing impairment
HP:0001328	Specific learning disability
Very rare (<4-1%)
HP:0001643	Patent ductus arteriosus

Run the differential on the 12 obligate / very frequent terms

Annotation source: 20301303[PMID]

Sources for this card

Orphanet page: orpha.net/en/disease/detail/648
This record as JSON: /data/d/648.json