Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information

Noonan's syndrome(NS)

MedGen UID:
18073
Concept ID:
C0028326
Congenital Abnormality
Synonyms: MAP2K1-Related Noonan Syndrome; NS; Pseudo-Turner syndrome
Modes of inheritance:
Heterogeneous
MedGen UID:
5539
Concept ID:
C0019409
Qualitative Concept
Made up of elements or ingredients that are not alike.
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
SNOMED CT: Noonan-Ehmke syndrome (205824006); Turner-like syndrome (205824006); Noonan syndrome (205824006); Turner phenotype, karyotype normal (205684007); Turner's phenotype, karyotype normal (205684007); Noonan's syndrome (205824006)
 
Genes: PTPN11; MAP2K1
Cytogenetic locations: 12q24.13; 15q22.31
OMIM: 163950

Disease characteristics

Excerpted from the GeneReview: Noonan Syndrome
Noonan syndrome (NS) is characterized by short stature, congenital heart defect, and developmental delay of variable degree. Other findings can include broad or webbed neck, unusual chest shape with superior pectus carinatum and inferior pectus excavatum, cryptorchidism, characteristic facies, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities. Although birth length is usually normal, final adult height approaches the lower limit of normal. Congenital heart disease occurs in 50%-80% of individuals. Pulmonary valve stenosis, often with dysplasia, is the most common heart defect and is found in 20%-50% of individuals. Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. Other structural defects include atrial and ventricular septal defects, branch pulmonary artery stenosis, and tetralogy of Fallot. Up to one third of affected individuals have mild intellectual disability.  [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Judith E Allanson  |  Amy E Roberts   view full author information

Additional descriptions

From OMIM
Noonan syndrome (NS) is an autosomal dominant disorder characterized by short stature, facial dysmorphism, and a wide spectrum of congenital heart defects. The distinctive facial features consist of a broad forehead, hypertelorism, downslanting palpebral fissures, a high-arched palate, and low-set, posteriorly rotated ears. Cardiac involvement is present in up to 90% of patients. Pulmonic stenosis and hypertrophic cardiomyopathy are the most common forms of cardiac disease, but a variety of other lesions are also observed. Additional relatively frequent features include multiple skeletal defects (chest and spine deformities), webbed neck, mental retardation, cryptorchidism, and bleeding diathesis (summary by Tartaglia et al., 2002). Genetic Heterogeneity of Noonan Syndrome See also NS3 (609942), caused by mutation in the KRAS gene (190070); NS4 (610733), caused by mutation in the SOS1 gene (182530); NS5 (611553), caused by mutation in the RAF1 gene (164760); NS6 (613224), caused by mutation in the NRAS gene (164790); NS7 (613706), caused by mutation in the BRAF gene (164757); and NS8 (615355), caused by mutation in the RIT1 gene (609591). See also NS2 (605275) for a possible autosomal recessive form of NS; Noonan syndrome-like disorder with loose anagen hair (NSLH; 607721), caused by mutation in the SHOC2 gene (602775); and Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia (NSLL; 613563), caused by mutation in the CBL gene (165360). Mutations in the neurofibromin gene (NF1; 613113), which is the site of mutations causing classic neurofibromatosis type I (NF1; 162200), have been found in neurofibromatosis-Noonan syndrome (NFNS; 601321).  http://www.omim.org/entry/163950
From GHR
Noonan syndrome is a condition that affects many areas of the body. It is characterized by mildly unusual facial characteristics, short stature, heart defects, bleeding problems, skeletal malformations, and many other signs and symptoms. People with Noonan syndrome have distinctive facial features such as a deep groove in the area between the nose and mouth (philtrum), widely spaced eyes that are usually pale blue or blue-green in color, and low-set ears that are rotated backward. Affected individuals may have a high arch in the roof of the mouth (high-arched palate), poor alignment of the teeth, and a small lower jaw (micrognathia). Many children with Noonan syndrome have a short neck and both children and adults may have excess neck skin (also called webbing) and a low hairline at the back of the neck. Approximately 50 to 70 percent of individuals with Noonan syndrome have short stature. At birth, they are usually of normal length and weight, but growth slows over time. Abnormal levels of growth hormone may contribute to the slow growth. Individuals with Noonan syndrome often have either a sunken chest (pectus excavatum) or a protruding chest (pectus carinatum). Some affected people may also have an abnormal side-to-side curvature of the spine (scoliosis). Most people with Noonan syndrome have a heart defect. The most common heart defect is a narrowing of the valve that controls blood flow from the heart to the lungs (pulmonary valve stenosis). Some affected individuals have hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood. A variety of bleeding disorders have been associated with Noonan syndrome. Some people may have excessive bruising, nosebleeds, or prolonged bleeding following injury or surgery. Women with a bleeding disorder typically have excessive bleeding during menstruation (menorrhagia) or childbirth. Adolescent males with Noonan syndrome typically experience delayed puberty. Affected individuals go through puberty starting at age 13 or 14 and have a reduced pubertal growth spurt. Most males with Noonan syndrome have undescended testicles (cryptorchidism), which may be related to delayed puberty or to infertility (inability to father a child) later in life. Females with Noonan syndrome typically have normal puberty and fertility. Noonan syndrome can cause a variety of other signs and symptoms. Most children diagnosed with Noonan syndrome have normal intelligence, but a small percentage has special educational needs, and some have intellectual disability. Some affected individuals have vision or hearing problems. Infants with Noonan syndrome may be born with puffy hands and feet caused by a buildup of fluid (lymphedema), which can go away on its own. Affected infants may also have feeding problems, which typically get better by age 1 or 2. Older individuals can also develop lymphedema, usually in the ankles and lower legs.  http://ghr.nlm.nih.gov/condition/noonan-syndrome

Clinical features

Neurofibrosarcoma
MedGen UID:
451960
Concept ID:
CN117588
Finding
A form of malignant cancer of the connective tissue surrounding nerves. Given its origin and behavior, it is classified as a sarcoma.
Cryptorchidism
MedGen UID:
504309
Concept ID:
CN000029
Finding
Absence of one or both testes from the scrotum owing to failure of the testis or testes to descend through the inguinal canal to the testis.
Hypogonadism
MedGen UID:
504359
Concept ID:
CN000131
Finding
A `decreased functionality` (PATO:0001624) of the `gonad` (FMA:18250).
High palate
MedGen UID:
504397
Concept ID:
CN000211
Finding
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Hypertelorism
MedGen UID:
504419
Concept ID:
CN000296
Finding
Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).
Cystic hygroma
MedGen UID:
427823
Concept ID:
CN000444
Finding
A cystic lymphatic lesion of the `neck` (FMA:7155).
Dental malocclusion
MedGen UID:
504556
Concept ID:
CN000647
Finding
Dental malocclusion refers to an abnormality of the occlusion, or alignment, of the teeth and the way the upper and lower teeth fit together, resulting in overcrowding of teeth or in abnormal bite patterns.
Hypertelorism
MedGen UID:
504419
Concept ID:
CN000296
Finding
Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).
Ptosis
MedGen UID:
504471
Concept ID:
CN000475
Finding
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
Myopia
MedGen UID:
504487
Concept ID:
CN000511
Finding
An abnormality of refraction characterized by the ability to see objects nearby clearly, while objects in the distance appear blurry.
Sensorineural hearing impairment
MedGen UID:
504436
Concept ID:
CN000380
Finding
A type of `hearing impairment` (HP:0000365) in one or both ears related to an `abnormal` (PATO:0000460) `functionality` (PATO:0001509) of the `cochlear nerve` (FMA:53431).
Hypogonadism
MedGen UID:
504359
Concept ID:
CN000131
Finding
A `decreased functionality` (PATO:0001624) of the `gonad` (FMA:18250).
Brachydactyly syndrome
MedGen UID:
500899
Concept ID:
CN001088
Finding
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used to describe a series of Mendelian diseases characterized by distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here, however, it is preferable to described the observed phenotypic abnormalities precisely.
Kyphoscoliosis
MedGen UID:
425109
Concept ID:
CN002496
Finding
An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane.
Cubitus valgus
MedGen UID:
428322
Concept ID:
CN002685
Finding
Abnormal positioning in which the elbows are turned out.
Defect in the atrial septum
MedGen UID:
504879
Concept ID:
CN001485
Finding
Atrial septal defect (ASD) is a congenital abnormality of the `interatrial septum` (FMA:7108) that enables blood flow between the left and right atria via the interatrial septum.
Hypertrophic cardiomyopathy
MedGen UID:
504884
Concept ID:
CN001492
Finding
Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.
Pulmonic stenosis
MedGen UID:
504885
Concept ID:
CN001495
Finding
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis) or just below the pulmonary valve (infundibular stenosis).
Patent ductus arteriosus
MedGen UID:
504886
Concept ID:
CN001496
Finding
In utero, the ductus arteriosus (DA) serves to divert ventricular output away from the lungs and toward the placenta by connecting the main pulmonary artery to the descending aorta. A patent ductus arteriosus (PDA) in the first 3 days of life is a physiologic shunt in healthy term and preterm newborn infants, and normally is substantially closed within about 24 hours after bith and completely closed after about three weeks. Failure of physiologcal closure is referred to a persistent or patent ductus arteriosus (PDA). Depending on the degree of left-to-right shunting, PDA can have clinical consequences.
Abnormal bleeding
MedGen UID:
504992
Concept ID:
CN001711
Finding
An abnormal susceptibility to bleeding, often referred to as a bleeding diathesis. A bleeding diathesis may be related to vascular, platelet and coagulation defects.
Reduced factor XII activity
MedGen UID:
505700
Concept ID:
CN004286
Finding
Decreased activity of `coagulation factor XII` (PR:000007296). Factor XII (fXII) is part of the intrinsic coagulation pathway and binds to exposed collagen at site of vessel wall injury, activated by high-MW kininogen and kallikrein, thereby initiating the coagulation cascade.
Amegakaryocytic thrombocytopenia
MedGen UID:
505707
Concept ID:
CN004304
Finding
Thrombocytopenia related to lack of or severe reduction in the count of megakaryocytes.
Reduced factor XIII activity
MedGen UID:
506216
Concept ID:
CN007351
Finding
Decreased activity of coagulation factor XIII (also known as fibrin stabilizing factor). Activated Factor XIII cross-links fibrin polymers solidifying the clot.

Professional guidelines

PubMed

Romano AA, Allanson JE, Dahlgren J, Gelb BD, Hall B, Pierpont ME, Roberts AE, Robinson W, Takemoto CM, Noonan JA
Pediatrics 2010 Oct;126(4):746-59. Epub 2010 Sep 27 doi: 10.1542/peds.2009-3207. [Epub ahead of print] PMID: 20876176

External

DYSCERNE, Management of Noonan Syndrome. A Clinical Guideline by the Noonan Syndrome Guideline Development Group, 2010

Recent clinical studies

Etiology

Hulselmans M, Benit E
Acta Cardiol 2010 Feb;65(1):89-92. PMID: 20306897
Sinis N, Lanaras TI, Kraus A, Werdin F, Schaller HE, Peek A
Microsurgery 2009;29(6):486-9. doi: 10.1002/micr.20625. PMID: 19296530
Delgado-López PD, Martín-Velasco V, Galacho-Harriero AM, Castilla-Díez JM, Rodríguez-Salazar A, Echevarría-Iturbe C
Neurocirugia (Astur) 2007 Jun;18(3):241-6. PMID: 17622464
Takagi M, Miyashita Y, Koga M, Ebara S, Arita N, Kasayama S
Calcif Tissue Int 2000 Mar;66(3):200-3. PMID: 10666495
Grange CS, Heid R, Lucas SB, Ross PL, Douglas MJ
Can J Anaesth 1998 Apr;45(4):332-6. doi: 10.1007/BF03012024. PMID: 9597207

Diagnosis

Tozzi RJ, Abdel-Razek AM, Kipel G, Gardin JM
J Am Coll Cardiol 2013 Aug 13;62(7):643. Epub 2013 Jun 7 doi: 10.1016/j.jacc.2013.01.105. [Epub ahead of print] PMID: 23747783
Hulselmans M, Benit E
Acta Cardiol 2010 Feb;65(1):89-92. PMID: 20306897
Delgado-López PD, Martín-Velasco V, Galacho-Harriero AM, Castilla-Díez JM, Rodríguez-Salazar A, Echevarría-Iturbe C
Neurocirugia (Astur) 2007 Jun;18(3):241-6. PMID: 17622464
Agras PI, Baskin E, Sakallioglu AE, Arda IS, Ayter S, Oguzkan S, Derbent M, Alehan F, Hicsonmez A, Saatci U
J Child Neurol 2003 Jan;18(1):68-72. PMID: 12661943
Kurose A, Oyama K, Murakami Y, Ohyama K, Segawa I, Sawai T
Hum Pathol 2000 Jun;31(6):764-7. doi: 10.1053/hupa.2000.7635. PMID: 10872673

Therapy

Sinis N, Lanaras TI, Kraus A, Werdin F, Schaller HE, Peek A
Microsurgery 2009;29(6):486-9. doi: 10.1002/micr.20625. PMID: 19296530
Sharma PR, MacFadyen UM, Fung DE
Dent Update 2007 Mar;34(2):117-8, 120. PMID: 17432776
Sgouros SN, Karamanolis G, Papadopoulou E, Papageorgiou G, Stefanides G, Nastos H, Mantides A
J Gastroenterol Hepatol 2004 Oct;19(10):1217-9. doi: 10.1111/j.1440-1746.2004.02931.x. PMID: 15377306
Aggarwal A, Krishnan J, Kwart A, Perry D
South Med J 2001 Apr;94(4):432-4. PMID: 11332913
Takagi M, Miyashita Y, Koga M, Ebara S, Arita N, Kasayama S
Calcif Tissue Int 2000 Mar;66(3):200-3. PMID: 10666495

Prognosis

Hulselmans M, Benit E
Acta Cardiol 2010 Feb;65(1):89-92. PMID: 20306897
Sinis N, Lanaras TI, Kraus A, Werdin F, Schaller HE, Peek A
Microsurgery 2009;29(6):486-9. doi: 10.1002/micr.20625. PMID: 19296530
Kiyota A, Tsukimori K, Yumoto Y, Hojo S, Morokuma S, Fukushima K, Takahata Y, Nakayama H, Wake N
Fetal Diagn Ther 2008;24(4):499-502. Epub 2009 Jan 17 doi: 10.1159/000193364. [Epub ahead of print] PMID: 19151555
Delgado-López PD, Martín-Velasco V, Galacho-Harriero AM, Castilla-Díez JM, Rodríguez-Salazar A, Echevarría-Iturbe C
Neurocirugia (Astur) 2007 Jun;18(3):241-6. PMID: 17622464
Takagi M, Miyashita Y, Koga M, Ebara S, Arita N, Kasayama S
Calcif Tissue Int 2000 Mar;66(3):200-3. PMID: 10666495

Clinical prediction guides

Noordam C, Van der Burgt I, Sengers RC, Delemarre-van de Waal HA, Otten BJ
Acta Paediatr 2001 Aug;90(8):889-94. PMID: 11529537
Bertola DR, Kim CA, Sugayama SM, Albano LM, Wagenführ J, Moysés RL, Gonzalez CH
Arq Bras Cardiol 2000 Nov;75(5):409-12. PMID: 11080752
Takagi M, Miyashita Y, Koga M, Ebara S, Arita N, Kasayama S
Calcif Tissue Int 2000 Mar;66(3):200-3. PMID: 10666495
Bawle EV, Black V
Am J Dis Child 1986 Aug;140(8):758-60. PMID: 3728401
Tejani A, Del Rosario C, Arulanantham K, Alpert LI
J Urol 1976 Feb;115(2):209-11. PMID: 765504

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...