(NS) is a relatively common
Congenital genetic condition which affects both males and females. 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. NS is one of the most common conditions associated with congenital heart anomalies, especially those of the right heart. The
Syndrome is named after Dr Jacqueline Noonan, a
Paediatric Cardiologist based in Kentucky.
It is believed that 1 in 1,000 to 1 in 2,500 children worldwide are born with Noonan syndrome. It is one of the most common genetic syndromes associated with congenital heart malformations, similar in frequency to
Down Syndrome . However, the features can vary greatly in patients with NS, thus diagnosis can often be delayed.
Recurrence in siblings and apparent transmission from parent to child has long suggested a genetic defect with
Autosomal Dominant inheritance and variable expression. A clearly affected person had up to a 50% chance of transmitting it to a child. The fact that affected parents cannot be identified for many children with Noonan syndrome suggests that (1) a parent could carry the gene without being affected, (2) that manifestations were variably expressed and could be so subtle as to go unrecognized, (3) that a high proportion of cases represented new, sporadic
Mutation s, or (4) that Noonan syndrome is heterogeneous, comprised of more than one similar condition of differing cause, some not inherited.
In most of the families with multiple affected members, Noonan syndrome mapped to
Receptor . The latter pathway is important in the formation of the cardiac semilunar
Valve s.
Noonan syndrome has been assigned
OMIM number 163950
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The most prevalent (common) signs are highlighted in with frequency listed in parentheses.
—''(2/3 of patients have a heart defect)''
: —''(50%)''
:Septal defects:
Atrial —''(10%)'' or
Ventricular —''(less common)''
:
Heart Murmur
:
Cardiomyopathy
:
Failure To Thrive as an infant
:
Decreased Appetite
:Faddy eater
:Digestive/Intestinal problems
:Frequent or forceful
Vomiting
:
Swallowing Difficulties
: — ''(almost all males)''
:Posterior cervical
Hygroma (webbed neck)
:
Lymphedema (build-up of body fluid due to poor functioning of the lymphatic system)
:
Delayed Puberty
:
Lack Of Sexual Development
:
Clumsiness
:
Poor Coordination
:
Motor Delay
: ''—(1/3 of pts have mild MR)''
:
Learning Disabilities
:Speech and
Language Delays
:Severe
Joint Pain or
Muscle Pain often with no identifiable cause
:
Osteoporosis
—''(bleeding disorders are fairly common although often although there is an evident bleeding problem, no specific factor deficiency can be found)''
:Easy bruising
:
Vasculitis (blood vessel inflammation; many types and causes)
:
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
:
Short Stature
:Cervical (neck) spine fusion
:
Scoliosis
: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)
:
Distended Abdomen
:
:
:
Large Head
:Small head (
Microcephaly )
:Triangular face shape
:Broad forehead
:Short neck, webbed neck, posterior cervical
:
Curly Hair
: —''(95%)''
:Drooping of the eyelids (
Ptosis )
: (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
:Small, upturned nose
: —''(over 90%)''
: —''(over 90%)''
: (outer rim) —''(over 90%)''
:Incomplete folding of ears
:Chronic
Otitis Media (ear infections)
:
Glue Ear (thick glue-like fluid behind ear drum)
: (top lip line) —''(over 90%)''
:
Micrognathia (small mouth)
:High Arched palate
:Dental problems
:
Hypernasality
:Articulation Difficulties
:Poor tongue control
:Bluntly ended fingers
:Extra padding on fingers and toes
:
Simian Crease s; deeply grooved palms and bottoms of feet
:
Edema of the back of hands and tops of feet
:
Cubitus Valgus (elbow deformity)
:
Polydactyly (having extra fingers or toes)
:
Hirsutism (excessive body hair growth)
:Cutaneous
Lymphangioma (wart-like growth on the skin, very small, made up of abnormal lymph vessels)
:
Keloids (scar
Hypertrophy )
:
Hyperkeratosis - overdevelopment of outer skin layer
:
Pigmented Nevi (birthmark)
:
Vitiligo (unpigmented patches on the skin)
Despite identification of a candidate gene, 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 the PTPN11 gene, however absence of the gene will not exclude the diagnosis as they believe that there are at least 2 more genes that cause NS. The principal values of making such a diagnosis are that it suggests other problems to check for, it excludes other possible explanations for the features, and it suggests the possibility of recurrence risk in siblings or offspring of the patient.
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 improve shortness. Learning problems should be ameliorated by determining a child's optimal learning conditions. Behavior problems can usually be helped by counseling the family.
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 1960's that the condition became commonly referred to as Noonan syndrome.
Jacqueline Noonan 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.
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.
- Turner Syndrome — a different disorder which is often confused with Noonan syndrome because of several physical features that they have in common.
