Genetic counseling: Noonan Syndrome

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Noonan Syndrome

Introduction and contracting[]

What is your primary concern
Do you have any questions for us today
What are your expectations for your visit today

Outline the session[]

We will be taking medical history information
Dr. ___ will come in to perform a physical examination
We will be discussing if we think there is a diagnosis that can be made at this time
If a diagnosis is made we will explain the inheritance and information we know about the cause

Medical history[]

(follow form)

Overview of Noonan Syndrome[]

Common autosomal dominant, single gene
Mistakenly called male Turner syndrome due to similar characteristics
Occurs in both males and females equally

Characteristics of Noonan Syndrome[]

Short stature
Congenital heart defects
Broad or webbed neck
Unusual chest shape (low set nipples, superior pectus carinatum, inferior pectus excavatum)
Developmental delay
Cryptorchidism
Characteristic physical appearance changes over time

Features irrespective of age[]

Low set posteriorly rotated ears with thick helix (90%)
Vivid blue or blue-green eyes (lighter than expected for background)
thickened or ptotic eyelids
hypertelorism

Neonate and Infancy[]

(age features are most striking)

tall forehead
hypertelorism with downslant palpebral fissures (95%)
prominent eyes
Nose has depressed root, wide base, bulbous tip
Deeply grooved philtrum
High wide peaks to vermillion border of upper lip
Excess nuchal skin and low posterior hairline

Children[]

Facial appearance lacks expression (resembles individual with myopathy)

Adolescence[]

Facial shape inverted triangle, wide forehead tapered chin
Pinched nasal root and thin bridge
Neck lengthens accentuates skin webbing or trapezius muscle
Eyes less prominent
Curly or wooly hair in older child

Adult[]

Nasolabial folds prominent
Skin appears transparent and wrinkled
- Genetics of Noonan syndrome
  - missense mutations in gene PTPN11 at 12q24.1 identified in 50% of patients
  - gene identified in 2001 (normal gene encodes protein-tyrosine phosphatase, non-receptor type 11 seems to be essential in several intracellular signal transduction pathways controlling diverse developmental processes
  - absence of this mutation in some families suggests heterogeneity
  - AD single gene
  - 50% chance to pass on if affected
  - if parents not affected chance is low <1% (gene clinics)
  - direct transmission reported 30-75% of time rest are de novo
  - predominantly mothers not fathers transmit gene (3:1 ratio) (likely due to cryptorchidism and reduced fertility in males)

Prevalence[]

1/1000-1/2,500

Diagnostic testing[]

Testing for PTPN11 mutations available on research basis
Diagnosis based on clinical findings though
High-resolution ultrasound only prenatal test available

Differential Diagnosis[]

Turner syndrome in females should be ruled out through karyotype
Trisomy 8p, trisomy 22 mosaicism, sex chromosome rearrangement, in utero exposure to alcohol or primidone
Williams, Aarskog, Baraitser-Winter, Costello syndromes share some features
Multiple lentigines/LEOPARD syndrome can also have pulmonary valve dysplasia, cardiomyopathy, short stature, hypertelorism, pectus deformity, hearing loss, developmental delay
Watson syndrome shares pulmonary valve stenosis, short stature, mild intellectual handicap, café-au-lait patches
Cardio-facio-cutaneous syndrome lot of overlap and debate about whether same condition, but MR more severe, skin findings hyperkeratosis, ichthyosis, absent eyebrows, sparse hair, gastrointestinal problems more severe, eyes rarely characteristically light blue/ blue-green

Cause of characteristics[]

Hypothesized to be consequences of lymphatic obstruction

Growth and feeding[]

B.W. usually normal
15% have poor suck, 38% poor suck and vomiting, 24% require tube feeding 2 weeks or more
length at birth normal usually then follows 3% ile
final height lower end of normal in adults
some endocrinologists choose to treat with growth hormone even if deficiency not seen

Development and behavior[]

Delayed milestones
Mean age sitting 10 mth, walking 21 mth, two-word sentence 31 mth
10-15 % require special ed
IQ usually within normal range, but mild MR seen in 1/3
Verbal lower than nonverbal performance
Usually good peer, social interactions and self-esteem, but one study suggests that less socially competent and more behavior problems than sibs (not clinically significant)

Ears and hearing[]

May cause delayed speech
Reported in >1/3 usually secondary to ottitis media
Sensorineural loss in 3%

Cardiovascular[]

Potential bias in frequency due to requirement for diagnosis by many (50-80%)
Stenotic or dysplastic pulmonary valve most common (20-50%)
7% of all children with pulmonary stenosis have Noonan
hypertrophic cardiomyopathy (20-30%) found at birth, infancy or childhood
ASD (10-20%)
VSD (5-15%)
Coarctation of aorta (9%)
Others
ECG abnormality found in 87-90%

Eye Problems (occur in up to 95%)[]

Strabismus (48-63%)
Refractive errors (60-70%)
Amblyopia (33%)
Nystagmus (9%)
Other problems common

Blood/ liver spleen[]

1/3 have coagulation problems
2/3 give history of abnormal bleeding or mild-severe bruising
hepatosplenomegaly occurs reason unknown(clinically evident 25% ultrasound 51%)
should avoid aspirin

various lymphatic abnormalities described[]

Genitourinary[]

Renal abnormalities (generally mild 11%)
Cryptorchidism in 60-80% of males may cause deficient spermatogenesis
Fertility is rule in females

Skin[]

Follicular keratosis
Scalp hair curly, thick and wooly, or sparse with easy breakage
Café-au-lait spots and lentigines more frequent than general population

Management if suspected[]

Physical and neuro exam
Plot growth on NS charts
Cardiology eval
Ophthalmology
Hearing
Coagulation screen
Renal ultrasound
Clinical and x-ray of spine and rib cage
Develop eval
Genetics consult

Psychosocial considerations[]

Diagnosis may not be certain
Difficulty and stress of having child with health concerns or learning issues
Guilt if passed on the gene

Support resources[]

The Noonan Syndrome Support Group

PO box 145

Upperco, MD 21155

Phone: 410-374-5345

Email: info@noonansyndrome.org

Website:www.noonansyndrome.org

MAGIC Foundation for Children's Growth

1327 North Harlem Ave

Oak Park, IL 60302

Phone: 708-383-0899

Email: mary@magicfoundation.org

www.magicfoundation.org

References[]

Management of Genetic Syndromes, Edited by Suzanne b. Cassidy and Judith e. Allanson. 2001. Wiley-Liss Inc. Chapter 15 written by Judith E. Allanson.
Gene Clinics: Noonan Syndrome

Notes[]

The information in this outline was last updated in 2002.

This material has been imported fom the wikibook "Genetic counseling"[ http://en.wikibooks.org/wiki/Genetic_counseling] under the GNU Free Documentation License.

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