NOONAN SYNDROME
 
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NOONAN SYNDROME

 

DEFINITION:

A disorder of unknown etiology with phenotypic features similar to those of Turner Syndrome.

EPIDEMIOLOGY:

  • incidence: 1/1,000-1/2,500 live births
  • age of onset:
    • newborn
  • risk factors:
    • familial - autosomal dominant with variable expression (sporadic cases thought to represent de novo mutations)
    • chrom.#: ?
    • gene: ?
  • M = F

PATHOGENESIS:

1. Etiology

  • unknown, but may be similar to that hypothesized for Turner Syndrome
  • genetic defect -> lymphangiectasia during a critical period in perinatal development -> disruption of normal tissue migration and organ placement by lymphedema -> Noonan phenotypes
  • in support of this hypothesis, cystic hygromas and edema have been detected prenatally in suspected cases

CLINICAL FEATURES:

1. Craniofacial Dysmorphisms

1. Newborn

  • hypertelorism with down-slanting palpebral fissures (95%)
  • deeply-grooved philtrum (95%)
  • low-set posteriorly-rotated ears with thick helix (90%)
  • low posterior hairline (55%)
  • high-arched palate (45%)
  • micrognathia (25%)

2. Infancy

  • large head with turricephaly
  • hypertelorism with prominent eyes and level palpebral fissures
  • thick-hooded eyelids or ptosis
  • nose with depressed root, wide base, and bulbous tip

3. Childhood

  • face appears coarse or myopathic then triangular
  • neck lengthens accentuating the webbing

4. Adolescence

  • eyes less prominent
  • nose with pinched root, wide base, and thinner higher bridge

5. Adult

  • prominent nasolabial folds
  • high anterior hairline
  • transparent wrinkled skin

2. Organ Malformations

1. Central Nervous System Manifestations

  • articulation abnormalities (72%)
  • mild-moderate mental retardation (33%)
  • gross motor developmental delay (25%)
  • speech and language developmental delay (20%)
  • mild hearing loss (12%)

2. Cardiovascular Manifestations

1. Congenital Heart Malformations (66%)

  • pulmonary valve stenosis (50%)
  • ASD (10%)
  • asymmetric septal hypertrophy (10%)

3. Endocrine Manifestations

1. Short Stature

  • birth: 40% have a normal birth weight
  • infancy: 40% failure to thrive
  • infancy -> puberty: 60% grow along the 3rd% with a normal growth velocity
  • adolescence : growth spurt reduced or absent
  • adult (untreated) : short stature (lower limit of normal)

2. Fertility

1. Males
  • 60% have cryptorchidism (usually bilateral) -> deficient spermatogenesis
  • small testes
  • delayed and/or inadequate development of secondary sexual characteristics
2. Females
  • normal or delayed development of secondary sexual characteristics
  • normal fertility
  • the 3x greater maternal transmission of the gene over male transmission is thought to be due to male infertility due to crytorchidism

4. Musculoskeletal Manifestations

  • pectus carinatum superiorly with pectus excavatum inferiorly (70%)
  • cubitus valgus (50%)
  • dental malocclusion (35%)
  • clinobrachydactyly with blunt finger-tips (30%)
  • vertebral/sternal anomalies (25%)

5. Other Manifestations

1. Ocular

  • keratoconus, myopia
  • strabismus, nystagmus

2. Hematology (20%)

  • various bleeding anomalies - platelet dysfunction, Factor XI Deficiency, von Willebrand Disease

3. King Syndrome

  • Noonan phenotype + malignant hyperthermia

INVESTIGATIONS:

1. Karyotype

  • normal: male (XY), female (XX)

2. Imaging Studies

  • 2D Echo, ECG
  • Skeletal X-rays

3. Serum

  • CBC, Factors XI, VIIIwW

MANAGEMENT:

1. Supportive

  • multidisciplinary approach
    • Paediatrics, Cardiology, Endocrinology, Orthopedics,
    • Ophthalmology, Hematology

2. Surgery

  • for cryptorchidism

 

 

 

Pediatric Database - NOONAN SYNDROME

 

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