II. Epidemiology
- Autosomal Dominant in 40% of cases (Sporadic in 60% of cases)
- Incidence
III. Pathophysiology
-
Genetic mutation affecting RAS/Mitogen-Activated Protein Kinase (MAPK)
- Protein Tyrosine phosphatase non-receptor type 11 gene mutation (PTPN11) is causative in 50% of cases
- Affects Cell Cycle
IV. Signs: Prenatal (Ultrasound and lab)
- Increased Nuchal Translucency
- Polyhydramnios
- Hydrothorax
- Abnormal maternal Triple Screen
V. Signs: Newborn
- Head large in contrast to a small face
- Tall forehead and narrow temples
- Wide-spaced eyes (Hypertelorism)
- Palpebral fissure (at canthus) slants downward
- Epicanthal folds
- Wide, depressed nose with upturned bulbous tip
- Small chin
- Short neck and increased nuchal skin
- Ears rotated back
- Dorsal hand and foot edema
VI. Signs: Infant
- Wispy Hair
- Eyes prominent with Droopy Eyelids
- Wide, depressed nose with upturned bulbous tip
- Philtrum deeply grooved resulting in an upper lip with cupid's bow shape
VII. Signs: Child or Teen
- Curly, wool-like hair
- Wide forehead
- Small chin
- Webbed Neck
- Wide-spaced nipples
- Pectus Excavatum or pectus carnitum (inferior Sternum depressed)
- Cubitus valgus (Forearm laterally deviated)
- Head in shape of an inverted triangle
VIII. Signs: Adult
- High anterior hairline
- Head in shape of an inverted triangle
- Nasolabial folds prominent
- Prominent skin Wrinkles
IX. Associated Conditions
-
Congenital Heart Disease
- Pulmonic Stenosis
- Hypertrophic Cardiomyopathy
- Hematologic disorders
- Bleeding Disorders (Platelet or Clotting Factor disorder)
- Leukemia or myeloproliferative disorder
- Lymphedema
- Growth disorder
- Failure to Thrive (and feeding difficulties)
- Short Stature (in 50-70% of cases)
- Final adult height in males: 63-66 in
- Final adult height in females: 59-61 in
- Genitourinary
- Delayed Puberty
- Male Infertility
- Cryptorchidism
- Renal malformation (e.g. duplex collecting system, solitary Kidney)
- Musculoskeletal
- Chest deformity (Pectus Excavatum or Pectus carnitum)
- Scoliosis
- Talipes Equinovarus
- Cubitus valgus
- Neurologic
- Normal intelligence in most patients
- Developmental Delay, Learning Disorders and speech disorders may occur
- Eye Disorders: Visual deficit
- Ear Disorders
- Skin Disorders
- Dystrophic Nails
- Prominent finger pad and toe pads
- Elastic skin
- Numerous Lentigines
X. Differential Diagnosis
-
Turner Syndrome
- Similar phenotypic features, but Noonan Syndrome has a normal karyotype and occurs in both males and females
- Cardio-facio-cutaneous syndrome
- Costello Syndrome
- LEOPARD Syndrome
- Acronym: Lentigines, EKG abnormalities, ocular Hypertelorism, pulmonary stenosis, abnormal genitalia, retardation of growth, Deafness
- Neurofibromatosis 1
- Watson Syndrome
XI. Diagnosis: Two or more positive criteria consistent with Noonan Syndrome
- Characteristic facial features (see signs above)
- Developmental Delay
- Delayed Puberty or Infertility
- Short Stature (<10% and especially if <3%)
- Pectus Excavatum or pectus carnitum
- Cryptorchidism (Undescended Testes)
- First degree relative diagnosed with Noonan Syndrome (or with suggestive features)
-
Congenital Heart Disease
- Especially Pulmonic Stenosis, Hypertrophic Cardiomyopathy or EKG abnormalities)
XII. Resources
- Genetics Home Reference