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Encyclopedia > Noonan syndrome
Noonan syndrome
Classification & external resources
ICD-10 Q87.1
ICD-9 759.89
OMIM 163950
DiseasesDB 29094
MedlinePlus 001656
eMedicine ped/1616 
MeSH D009634

Noonan Syndrome (NS) is a relatively common congenital genetic condition which affects both males and females. It used to be referred to as the male version of Turner's syndrome[1]; however, the genetic causes of Noonan syndrome and Turner syndrome are distinct. The principal features include congenital heart malformation, short stature, learning problems, indentation of the chest, impaired blood clotting, and a characteristic configuration of facial features. The syndrome is named after Dr Jacqueline Noonan, a pediatric cardiologist born October 28, 1921 in Burlington, Vermont; she is now based in Kentucky. The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) is a coding of diseases and signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or diseases, as classified by the World Health Organization (WHO). ... // Q00-Q99 - Congenital malformations, deformations and chromosomal abnormalities (Q00-Q07) Congenital malformations of the nervous system (Q00) Anencephaly and similar malformations (Q01) Encephalocele (Q02) Microcephaly (Q03) Congenital hydrocephalus (Q04) Other congenital malformations of brain (Q05) Spina bifida (Q06) Other congenital malformations of spinal cord (Q07) Other congenital malformations of nervous... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... The Disease Bold textDatabase is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... MedlinePlus (medlineplus. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... A congenital disorder is a medical condition or defect that is present at or before birth (for example, congenital heart disease). ... In medicine, the term syndrome is the association of several clinically recognizable features, signs, symptoms, phenomena or characteristics which often occur together, so that the presence of one feature alerts the physician to the presence of the others. ... Pediatrics (also spelled paediatrics or pædiatrics) is the branch of medicine that deals with the medical care of infants and children. ... ... Official language(s) English[1] Capital Frankfort Largest city Louisville Area  Ranked 37th  - Total 40,444 sq mi (104,749 km²)  - Width 140 miles (225 km)  - Length 379 miles (610 km)  - % water 1. ...

It is believed that between approximately 1 in 1,000 and 1 in 2,500 children worldwide are born with NS. It is one of the most common genetic syndromes associated with congenital heart disease, similar in frequency to Down syndrome. However, the range and severity of features can vary greatly in patients with NS. Therefore, the syndrome is not always identified at an early age.



NS may be inherited in an autosomal dominant pattern with variable expression.

Recurrence in siblings and apparent transmission from parent to child has long suggested a genetic defect with autosomal dominant inheritance and variable expression. A person with NS has up to a 50% chance of transmitting it to a child. The fact that an affected parent is not always identified for children with NS suggests several possibilities: Image File history File links Autodominant2. ... Image File history File links Autodominant2. ... It has been suggested that this article or section be merged into Dominance relationship. ... It has been suggested that this article or section be merged into Dominance relationship. ...

  1. a parent could carry the gene without being affected (incomplete penetrance)
  2. manifestations are variably expressed and could be so subtle as to go unrecognized (variable expressivity)
  3. a high proportion of cases represent new, sporadic mutations or
  4. Noonan syndrome is heterogeneous, comprising more than one similar condition of differing cause, some not inherited.

In most of the families with multiple affected members, NS maps to chromosome 12q24.1. In 2001, it was reported that approximately half of a group of patients with Noonan syndrome carried a mutation of the PTPN11 gene at that location, which encodes protein tyrosine phosphatase SHP-2.[2] The SHP2 protein is a component of several intracellular signal transduction pathways involved in embryonic development that modulate cell division, differentiation, and migration, including that mediated by the epidermal growth factor receptor. The latter pathway is important in the formation of the cardiac semilunar valves. It has recently been shown that activating mutations in SOS1 also give rise to NS.[3] Shp2 and SOS1 both have roles as positive regulators of the Ras/MAP kinase pathway suggesting that dysregulation of this pathway may play a major role in the genesis of this syndrome.[4] Additional mutations in KRAS [5] and RAF1[6] genes have been reported to cause Noonan syndrome in a smaller percentage of individuals with the syndrome. Penetrance is a term used in genetics that describes the extent to which the properties controlled by a gene, its phenotype, will be expressed. ... Expressivity refers to variations of a phenotype in genetics. ... It has been suggested that mutant be merged into this article or section. ... Look up Heterogeneous in Wiktionary, the free dictionary. ... Chromosome 12 is one of the 23 pairs of chromosomes in humans. ... In biology, signal transduction refers to any process by which a cell converts one kind of signal or stimulus into another, most often involving ordered sequences of biochemical reactions inside the cell, that are carried out by enzymes and linked through second messengers resulting in what is thought of as... Epidermal Growth Factor or EGF is a 6045 Da protein with 53 amino acid residues and three intramolecular disulfide bonds. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... Grays Fig. ... SOS1 (Son of Sevenless 1) is gene encoding a GTPase activating protein that acts as a nucleotide exchange factor for Ras-GTPase. ... In molecular biology, Ras is the name of a protein, the gene that encodes it, and the family and superfamily of proteins to which it belongs. ... In cell biology, mitogen-activated protein kinases (MAPKs) (EC 2. ...

Manifestations by organ system

The most prevalent (common) signs are highlighted in bold with frequency listed in parentheses.

HEART(2/3 of patients have a heart defect)

Pulmonary Valvular Stenosis(50%)
Septal defects: atrial(10%) or ventricular(less common)
Heart murmur

GASTROINTESTINAL SYSTEM Atrial septal defects (ASD) are a group of congenital heart diseases that enables communication between atria of the heart and may involve the interatrial septum. ... A ventricular septal defect (or VSD) is a defect in the ventricular septum (the wall dividing the left and right ventricles of the heart). ... Murmurs are abnormal heart sounds that are produced as a result of turbulent blood flow, which is sufficient to produce audible noise. ...

Failure to thrive as an infant
Decreased appetite
Digestive problems
Frequent or forceful vomiting
Swallowing difficulties

GENITO-URINARY SYSTEM Failure to thrive is a medical term which denotes poor weight gain and physical growth failure over an extended period of time in infancy. ... Anorexia (deriving from the Greek όρεξη (orexe) = appetite) is the decreased sensation of appetite. ... Vomiting (also throwing up or emesis) is the forceful expulsion of the contents of ones stomach through the mouth and sometimes the nose. ... Dysphagia is the medical term for the symptom of difficulty in swallowing. ...

Cryptorchidism (undescended testicles)(almost all males)

LYMPHATIC SYSTEM Cryptorchidism is a medical term referring to absence from the scrotum of one or both testes. ...

Posterior cervical Hygroma (webbed neck)
Lymphedema (build-up of body fluid due to poor functioning of the lymphatic system)

DEVELOPMENTAL Lymphangioma, a lymphatic malformation, is a benign proliferation of lymph vessels, and is rare, incidence estimated to be around 1 per 10 000 live births. ... Azskeptic 17:34, 10 July 2007 (UTC) Lymphedema, also spelled lymphoedema, also known as lymphatic obstruction, is a condition of localized fluid retention caused by a compromised lymphatic system. ...

Poor coordination
Motor delay
Mental retardation —(1/3 of patients have mild MR)
Learning disabilities
Speech and language delays

MUSCULOSKELETAL Look up clumsy, clumsiness in Wiktionary, the free dictionary. ... Mental retardation is a term for a pattern of persistently slow learning of basic motor and language skills (milestones) during childhood, and a significantly below-normal global intellectual capacity as an adult. ... In broad terms, the phrase learning disability covers any of a range of conditions that affect a persons ability to learn new information. ...

Severe joint pain or muscle pain often with no identifiable cause

HEMATOLOGIC In medicine, arthralgia (literally: joint pain, from arthros = joint and -algia denoting pain) is the presence of painful joints in the absence of frank arthritis. ... Myalgia means muscle pain and is a symptom of many diseases and disorders. ...

Easy bruising
Amegakaryocytic Thrombocytopenia (low platelet count)
Blood Clotting Disorders
Von Willebrand disease
Prolonged activated partial thromboplastin time
Partial deficiency of Factor VIII:C
Partial deficiency of Factor XI:C
Partial deficiency of Factor XII:C
Combined Coagulation deficiencies

Thrombocytopenia (or -paenia, or thrombopenia in short) is the presence of relatively few platelets in blood. ... Coagulation is the thickening or congealing of any liquid into solid clots. ... Von Willebrand disease (vWD) is the most common hereditary coagulation abnormality described in humans, although it can also be acquired as a result of other medical conditions. ... The partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT or APTT) is a performance indicator measuring the efficacy of both the intrinsic and the common coagulation pathways. ... Factor VIII (FVIII) is an essential clotting factor. ... Factor XI or plasma thromboplastin antecent is one of the enzymes ( EC 3. ... Hageman factor is a plasma protein now usually known as factor XII. It is part of the coagulation cascade and activates factor XI and prekallikrein. ...

By physical appearance


Short stature
Cervical (neck) spine fusion
Prominence of breast bone (pectus carinatum)
Depression of breast bone (pectus excavatum)
Joint contractures or tightness
Joint hyperextensibility or looseness
Growth retardation
Winging of the scapula
Hypotonia (low muscle tone)

HEAD People who are shorter have short stature. ... Pectus carinatum, also called pigeon chest, is a deformity of the chest characterized by a protrusion of the sternum. ... Pectus excavatum is a congenital deformity (often present at birth) of the sternum, which is pressed into the chest, resulting in a caved-in or sunken appearance. ... The term Delayed milestone (or developmental delays) is used to describe the condition where a child does not reach one of these stages at the expected age. ... Left scapula - front view () Left scapula - rear view () In anatomy, the scapula, or shoulder blade, is the bone that connects the humerus (arm bone) with the clavicle (collar bone). ... Hypotonia is a condition of abnormally low muscle tone (the amount of tension or resistance to movement in a muscle), often involving reduced muscle strength. ...

Excess skin on the back of the neck
Low hairline at the nape of the neck
Large head
Triangular face shape
Broad forehead
Short neck, webbed neck, posterior cervical
Curly hair

EYES Macrocephaly, a type of cephalic disorder, is a condition in which the head circumference is larger than average for the age and sex of the infant or child. ... For the musical, see Hair (musical). ...

Widely set eyes (hypertelorism)(95%)
Drooping of the eyelids (ptosis (eyelid))
Epicanthal folds (extra fold of skin at the inner corner of the eye)
Proptosis (bulging eyes)
Refractive visual errors
Inward or outward turning of the eyes (strabismus)
Nystagmus - jerking movement of the eyes

NOSE Hypertelorism is an abnormally increased distance between two organs or bodily parts, usually referring to an increased distance between the eyes (orbital hypertelorism), seen in a variety of syndromes, including DiGeorge syndrome and Loeys-Dietz syndrome. ... In ophthalmology, ptosis is an abnormally low position (drooping) of the upper eyelid which may grow more or less severe during the day. ... A young woman with an epicanthal fold on both eyes Eye with epicanthal fold An epicanthal fold, epicanthic fold, or epicanthus is a skin fold of the upper eyelid (from the nose to the inner side of the eyebrow) covering the inner corner (medial canthus) of the human eye. ... Exophthalmos is a bulging of the eye anteriorly out of the orbit. ... Strabismus (from Greek: στραβισμός strabismos, from στραβίζειν strabizein to squint, from στραβός strabos squinting, squint-eyed[1]) is a condition in which the eyes are not properly aligned with each other. ... Nystagmus is involuntary eye movement that can be part of the vestibulo-ocular reflex (VOR), with the eyes moving first in the direction of the lesioned side (slow phase) followed by a quick correction (fast phase) to the opposite side or away from the lesioned side. ...

Small, upturned nose


Low set ears(over 90%)
Backward rotated ears(over 90%)
Thick helix of ear (outer rim) —(over 90%)
Incomplete folding of ears
Chronic Otitis media (ear infections)

MOUTH/SPEECH Otitis media is inflammation of the middle ear: the small space between the ear drum and the inner ear. ...

Deeply grooved philtrum (top lip line) —(over 90%)
Micrognathia (undersized lower jaw)
High Arched palate
Dental problems
Articulation Difficulties
Poor tongue control

LIMBS/EXTREMITIES Micrognathia is a medical term for an unnaturally small jaw. ...

Bluntly ended fingers
Extra padding on fingers and toes
Edema of the back of hands and tops of feet
Cubitus valgus (elbow deformity)

SKIN This page is about the condition called edema. ... Cubitus valgus: A deformity of the elbow resulting in an increased carrying angle (so that, with the arm extended at the side and the palm facing forward, the forearm and hand are held at greater than 15 degrees). ...

Lymphedema (swelling of the extremities)
Keloids (scar hypertrophy)
Hyperkeratosis - overdevelopment of outer skin layer
Pigmented nevi (birthmark)

A keloid scar is a special case of a scar. ... Bodybuilder Markus Rühl has marked hypertrophy of skeletal muscle. ... Hyperkeratosis results when an excess of proteins called keratins are produced. ... Nevus (or naevus) is a general term that refers to a number of different, usually benign, pigmented lesions of the skin. ...


Despite identification of four causative genes, the diagnosis of Noonan syndrome is still based on clinical features. In other words, it is made when a physician feels that a patient has enough of the features to warrant the label indicating association. The patient can be tested for mutations in the PTPN11, SOS1, or KRAS genes, however absence of a mutation will not exclude the diagnosis as there are more as yet undiscovered genes that cause NS. The principal values of making such a diagnosis are that it guides additional medical and developmental evaluations, it excludes other possible explanations for the features, and it allows more accurate recurrence risk estimates.


Each specific abnormality can be treated as if it occurred in isolation. A congenital heart malformation can be corrected surgically. Undescended testes can be brought into the scrotum surgically. Growth hormone is sometimes given to address short stature. Learning problems should be ameliorated by determining a child's optimal learning conditions. Behavior problems can usually be helped by counseling the family. During male mammalian development, the testes normally descend from their original position in the abdomen to their final home, the scrotum. ... Growth hormone (GH) is a protein hormone secreted by the pituitary gland which stimulates growth and cell reproduction. ...


The first description of a patient with the features of Noonan syndrome was made by Koblinsky in 1883, although it was not until the late 1960s that the condition became commonly referred to as Noonan syndrome.

Jacqueline Noonan (born October 28, 1921 in Burlington, Vermont) is a pediatric cardiologist and pediatrician, now based in Kentucky, who qualified in Boston in 1956. When she subsequently began work at the University of Iowa as their first pediatric cardiologist, she noticed that children with a rare type of heart defect, valvular pulmonary stenosis, often had a characteristic physical appearance with short stature, webbed neck, wide spaced eyes, and low-set ears. Both boys and girls were affected. Even though these characteristics were sometimes seen running in families, chromosomes appeared grossly normal. She studied 833 patients at the congenital heart disease clinic, looking for other congenital abnormalities, and in 1962 presented a paper: "Associated non-cardiac malformations in children with congenital heart disease". This described 9 children who in addition to congenital heart disease had characteristic faces, chest deformities and short stature. Both males and females were found to be similarly affected, and the chromosomes were apparently normal. Not to be confused with Iowa State University. ... Pulmonary stenosis is a congenital medical condition in which outflow of blood from the right ventricle of the heart is obstructed at the level of the pulmonic valve. ... Karyogram of human male using Giemsa staining. ... Year 1962 (MCMLXII) was a common year starting on Monday (the link is to a full 1962 calendar) of the Gregorian calendar. ...

Dr John Opitz, a former student of Dr Noonan, first began to call the condition "Noonan Syndrome" when he saw children who looked like those whom Dr Noonan had described. Dr Noonan later produced a paper entitled "Hypertelorism with Turner Phenotype", and in 1971 at the Symposium of Cardiovascular defects, the name 'Noonan Syndrome' became officially recognized.

See also

  • Turner syndrome — a different disorder which is often confused with Noonan syndrome because of several physical features that they have in common.
  • Fetal alcohol syndrome — another disorder that is sometimes confused with Noonan syndrome because of some common facial features and mental retardation[7]
  • Leopard syndrome— A related disorder caused by mutations in PTPN11 that are catalytically inactivating.
  • Cardiofaciocutaneous syndrome — A related disorder which also affects genes encoding elements of the Ras/MAP kinase pathway.
  • PTPN11— a gene mutated in Noonan Syndrome and LEOPARD Syndrome
  • SOS1— a gene mutated in Noonan Syndrome
  • KRAS— A gene mutated in Noonan Syndrome and Cardiofaciocutaneous syndrome.
  • Dermatoglyphics

Fetal alcohol syndrome or FAS is a disorder of permanent birth defects that occurs in the offspring of women who drink alcohol during pregnancy. ... Postdlf 23:42, 15 Jun 2005 (UTC) Categories: Possible copyright violations ... Cardiofaciocutaneous Syndrome is an extremely rare and serious genetic condition. ... PTPN11 is a gene encoding the protein tyrosine phosphatase (PTP), Shp2. ... SOS1 (Son of Sevenless 1) is gene encoding a GTPase activating protein that acts as a nucleotide exchange factor for Ras-GTPase. ... An image of Italian Karst (Monfalcone). ... Dermatoglyphics (from ancient Greek derma = skin, glyph = carving) is the scientific study of fingerprints. ...


  1. ^ Curcić-Stojković O, Nikolić L, Obradović D, Krstić A, Radić A (1978). "[Noonan's syndrome. (Male Turner's syndrome, Turner-like syndrome)]". Med Pregl 31 (7-8): 299-303. PMID 692497. 
  2. ^ Tartaglia M, et al. Nature Genetics 2001;29:465-468
  3. ^ Roberts AE, et al. Nature Genetics Published online: 3 December 2006
  4. ^ Bentires-Alj M, et al. Nat Med. 2006; 12:283-285
  5. ^ Shubbert, S. et al. (2006) Germline KRAS mutations cause Noonan syndrome. Nature Genetics, 29, 465-468.
  6. ^ Razzaque, M. A. et al. Nature Genetics Published online: 1 July 2007
  7. ^ CDC. (2004). Fetal Alcohol Syndrome: Guidelines for Referral and Diagnosis. Can be downloaded at http://www.cdc.gov/fas/faspub.htm.

External links

  Results from FactBites:
Welcome (541 words)
Noonan Syndrome is a condition which affects both children and adults.
Noonan Syndrome is one of the most common of those conditions associated with congenital heart abnormality.
The Noonan Syndrome Support Group, Inc. is committed to the most accurate and current understanding of Noonan syndrome.
Syndrome Help And Advice | Syndrome Directory (556 words)
Treacher Collins Syndrome is an uncommon genetic disorder that causes craniofacial deformity: approximately 1 in 10,000 children are born with the syndrome.
Noonan Syndrome is a fairly common congenital (present at birth) genetic disorder which can affect either males or females: as many as 1 in 2,500 children are born with the condition.
Noonans Syndrome is one of the more common genetic disorders that is strongly connected to congenital heart problems.
  More results at FactBites »



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