Hypertrophic obstructive cardiomyopathy (HOCM) with asymmetrical septum hypertrophy is present in 20% of patients. [ojrd.biomedcentral.com]

Hypertrophic cardiomyopathy, found in 20%-30% of individuals, may be present at birth or develop in infancy or childhood. [ncbi.nlm.nih.gov]

Table 1 presents the genes currently known to be involved in NS. [analesdepediatria.org]

The condition is present from before birth, although milder cases may not be diagnosed until a child gets older. [nhs.uk]

In approximately one quarter of affected individuals, pigmented moles (nevi) may be present. [rarediseases.org]

• Prolonged Bleeding

  A variety of bleeding disorders have been associated with Noonan syndrome. Some affected individuals have excessive bruising, nosebleeds, or prolonged bleeding following injury or surgery. [medlineplus.gov]

  Coagulation studies reveal prolonged bleeding times, factor VIII, XI and XII deficiencies, thrombocytopaenia and platelet function defects. These manifestations appear individually or in combination [4, 17]. [ojrd.biomedcentral.com]

  Some affected individuals may have von Willebrand disease; an inherited condition characterized by deficiency of coagulation factor VIII, prolonged bleeding time, and impaired adhesion of platelets. [rarediseases.org]

• Lymphedema

  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. Older individuals can also develop lymphedema, usually in the ankles and lower legs. [medlineplus.gov]

  In addition, appropriate supportive measures may be used in affected individuals with lymphedema. Early intervention may be important in helping children with Noonan syndrome reach their potential. [rarediseases.org]

  Noonan syndrome in an adult family presenting with chronic lymphedema. Am J Med., 65 (1978), pp. 379-383 [28] A.A. Romano, J.E. Allanson, J. Dahlgren, B.D. Gelb, B. Hall, M.E. Pierpont, et al. [analesdepediatria.org]

  The lymphatic system develops abnormally in NS, although the persistence of lymphedema at birth occurs less frequently than observed in Turner syndrome. [karger.com]

• Infertility

  Most males with Noonan syndrome have undescended testes (cryptorchidism), which may contribute to infertility (inability to father a child) later in life. [medlineplus.gov]

  If not corrected surgically, male reproductive cells (spermatozoa) may fail to develop properly within the testes (deficient spermatogenesis), and some affected males may experience infertility (sterility). [rarediseases.org]

  The literature also describes a higher frequency of infertility in male patients with NS. In contrast, it appears that women with NS have normal fertility (which would explain why maternal transmission predominates in familial cases). [analesdepediatria.org]

• Epilepsy

  More significant neurological problems, such as epilepsy, are noted in a small minority of patients. [karger.com]

• Surgical Procedure

  Cardiac, arteriovenous, and/or lymphatic malformations that may be present must be taken into consideration during decisions concerning surgical procedures. [rarediseases.org]

• Failure to Thrive

  Neonatal feeding difficulties and failure to thrive are present in 63% of patients [4]. In general, these feeding problems resolve spontaneously later in infancy. Mean prepubertal growth parallels the 3rd centile for height and weight. [ojrd.biomedcentral.com]

  Feeding problems are noted in the majority of affected infants and can cause failure to thrive [Shah et al., 1999]. [karger.com]

  Some infants with Noonan syndrome may experience feeding problems and fail to grow and gain weight at the expected rate (failure to thrive). [rarediseases.org]

• High Arched Palate

  Affected individuals may have a high arch in the roof of the mouth (high-arched palate), poor teeth alignment, and a small lower jaw (micrognathia). [medlineplus.gov]

  […] posteriorly rotated ears with a thick helix, high arched palate, micrognathia, and a short neck with excess nuchal skin and a low posterior hairline. [ojrd.biomedcentral.com]

  palate (55%–100%), dental malocclusion (50%–67%), temporo-mandibular joint problems (72%) and micrognathia. [analesdepediatria.org]

• Low Set Ears

  Some of the characteristic features that are found in patients with Noonan syndrome, regardless of age, include: Low-set ears with posterior rotation and thickened helix Eyes that are often wide-spaced with vivid blue or blue-green irises Broad or webbed [news-medical.net]

  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. [medlineplus.gov]

  NS facial features and signs include high forehead, hypertelorism, downslanting palpebral fissures, epicantal folds, ptosis, low-set and/or posteriorly rotated ears (fig. 2). A short and/or webbed neck and a low posterior hairline commonly occur. [karger.com]

• Sparse Hair

  Approximately one-third of the patients have thick curly hair, and 10% have thin sparse hair. Foetal pads on fingers and toes are common (67%) [4]. [ojrd.biomedcentral.com]

• Darkly Pigmented Skin

  Most of them exhibited hairless and darkly pigmented skin with eczema or ichthyosis, and tendency to pruritus. Ectodermal anomalies also included sparse eyebrows and dystrophic or thin nails. [karger.com]

• Sparse Hair

  Approximately one-third of the patients have thick curly hair, and 10% have thin sparse hair. Foetal pads on fingers and toes are common (67%) [4]. [ojrd.biomedcentral.com]

• Eczema

  Most of them exhibited hairless and darkly pigmented skin with eczema or ichthyosis, and tendency to pruritus. Ectodermal anomalies also included sparse eyebrows and dystrophic or thin nails. [karger.com]

• Hypertelorism

  The main facial features of NS are hypertelorism with down-slanting palpebral fissures, ptosis and low-set posteriorly rotated ears with a thickened helix. [ojrd.biomedcentral.com]

  These include Costello syndrome, cardiofaciocutaneous syndrome, neurofibromatosis type 1, and LEOPARD syndrome (the acronym stands for multiple lentigines, ECG conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormal genitalia, retardation [news-medical.net]

  Characteristic features of the head and facial (craniofacial) area may include widely set eyes (ocular hypertelorism); skin folds that may cover the eyes’ inner corners (epicanthal folds); drooping of the upper eyelids (ptosis); a small jaw (micrognathia [rarediseases.org]

  The acronymic name refers to the major features: Lentigines, ECG conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, and sensorineural Deafness [Gorlin et al., 1971]. [karger.com]

  […] become less prominent in adulthood.2 The characteristics features are a triangular face shape (broadened forehead with narrowing down toward the chin), low-set posteriorly rotated ears with a thick helix (90%), downslanting palpebral fissures (95%), hypertelorism [analesdepediatria.org]

• Short Neck

  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. [medlineplus.gov]

  In the adolescent and young adult, the eyes are less prominent and the neck appears less short. Sometimes there is marked webbing or prominent trapezius. [ojrd.biomedcentral.com]

  There is redundant skin in the neck and a prominent trapezius. [analesdepediatria.org]

• Psychomotor Retardation

  In addition, affected individuals may experience abnormal delays in the acquisition of skills requiring the coordination of mental and muscular activity (psychomotor retardation), learning disabilities, and language delays that may potentially be due [rarediseases.org]

• Hyperactivity

  Some patients have learning difficulties and/or hyperactive behavior. [karger.com]

  These findings establish hyperactive Ras as a cause of developmental abnormalities seen in NS [37]. Diagnostic methods Noonan syndrome is a heterogeneous but clinically recognisable, multiple congenital anomaly syndrome. [ojrd.biomedcentral.com]

  Other psychiatric disorders described in these patients include mood disorders, difficulties with communication and interpersonal interaction and attention-deficit hyperactivity disorder.13 Language impairments are more frequent in children with NS compared [analesdepediatria.org]

• Left Axis Deviation

  Left axis deviation, small R waves in the left precordial leads, as well as giant Q waves are also characteristic findings. [news-medical.net]

  Electrocardiograms (ECG) from NS patients display wide QRS complexes with a predominantly negative pattern in the left precordial leads (62%). They also display left axis deviation and giant Q waves [5, 8]. [ojrd.biomedcentral.com]

  An EKG, which records the electrical activities of the heart muscle, may reveal abnormal electrical patterns (e.g., left axis deviation, left anterior hemiblock, deep S wave). [rarediseases.org]

  The literature also describes electrocardiographic abnormalities in these patients (50%).6 Frequently, these involve wide QRS intervals with a predominantly negative pattern in the left precordial leads and left axis deviation with giant Q waves, even [analesdepediatria.org]

Treatments for Noonan syndrome There's currently no single treatment for Noonan syndrome, but it's often possible to successfully manage many aspects of the condition. [nhs.uk]

If the patient exhibits a poor response despite 1–2 years of treatment at high doses, consider discontinuation of treatment, as the peak response should occur in the early years of treatment. [analesdepediatria.org]

Standard Therapies Treatment The treatment of Noonan syndrome is directed toward the specific complications that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. [rarediseases.org]

GH treatment in pharmacological doses can be used to accelerate growth during the first years of life. Initial reports on the long-term effects of this treatment show a beneficial effect [10, 11]. [ojrd.biomedcentral.com]

A recent prospective survey on the effect of long-term GH treatment on adult height in NS, however, documented a significant mean height gain, and did not confirm occurrence of bone age acceleration during the first years of GH treatment [Noordam et al [karger.com]

However, the prognosis for NS patients with JMML is better than that for non-NS patients with JMML [19, 20]. Lymphatic vessel dysplasia, hypoplasia, or aplasia are common findings in NS (20%). [ojrd.biomedcentral.com]

An absence of symptoms, a normal cardiac output and pulmonary arterial blood pressure and a right ventricular pressure of less than 100 mmHg are associated with a good prognosis.33 The mortality associated to hypertrophic cardiomyopathy is the same in [analesdepediatria.org]

Table 1 Scoring system for Noonan syndrome (NS) # Full size table Epidemiology The incidence of NS is reported to be between 1 in 1000 and 1 in 2500 live births [3, 4]. [ojrd.biomedcentral.com]

Subsequent studies performed with large, clinically well-characterized cohorts have provided an estimate of the relevance of PTPN11 mutations in the epidemiology of NS, and explored genotype-phenotype correlations [Tartaglia et al., 2002; Zenker et al [karger.com]

The role of RAS/MAPK hyper-activation in the pathophysiology of this group of disorders offers a unique opportunity for the development of targeted approaches. [analesdepediatria.org]

For example, severe heart defects may need to be repaired with surgery, and growth hormone medicine may be used to help prevent restricted growth. [nhs.uk]

[…] surgery to prevent, lower the risk of, or control abnormal bleeding. [rarediseases.org]

Since many patients undergo one or more operations, special care is required to prevent intraoperative or postoperative haemorrhage. Suitable blood products should be made readily accessible in case such complications arise [18]. [ojrd.biomedcentral.com]

Since many affected children will require interventional procedures such as balloon pulmonary valvuloplasty and orchidopexy, this is important to bear in mind to prevent significant hemorrhagic complications. [karger.com]