Disability
Noonan Syndrome
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Noonan Syndrome
Epidemiology
Autosomal Dominant
in 40% of cases (Sporadic in 60% of cases)
Incidence
Severe
Phenotype
: 1 in 1000 to 2500
Mild
Phenotype
: 1 in 100
Pathophysiology
Gene
tic 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
Signs
Prenatal (
Ultrasound
and lab)
Increased
Nuchal Translucency
Polyhydramnios
Hydrothorax
Abnormal maternal
Triple Screen
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
Signs
Infant
Wispy
Hair
Eyes prominent with
Droopy Eyelid
s
Wide, depressed nose with upturned bulbous tip
Philtrum deeply grooved resulting in an upper lip with cupid's bow shape
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
Signs
Adult
High anterior hairline
Head in shape of an inverted triangle
Nasolabial folds prominent
Prominent skin
Wrinkle
s
Associated Conditions
Congenital Heart Disease
Pulmonic Stenosis
Hypertrophic Cardiomyopathy
Hematologic disorders
Bleeding Disorder
s (
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 Disorder
s and speech disorders may occur
Eye Disorders: Visual deficit
Strabsimus
Nystagmus
Cataract
s
Ear Disorders
Sensorineural Hearing Loss
Deafness
Skin Disorders
Dystrophic Nail
s
Prominent finger pad and toe pads
Elastic skin
Numerous
Lentigines
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
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)
Resources
Genetics
Home Reference
http://ghr.nlm.nih.gov/condition/noonan-syndrome
References
Bhambhani (2014) Am Fam Physician 89(1): 37-43 [PubMed]
Romano (2010) Pediatrics 126(4): 746-59 [PubMed]
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