Transcript Noonan syndrome - Lakshmi Hospital

DR.S.M.THIRUNUAVUKKARASU
MD (GM)., DMRD., D.Diab., F.Echo.,
DEPARTMENT OF MEDICINE
GOVT. THENI MEDICAL COLLGE
THENI
46 YEAR FEMALE FORM A VILLAGE NEAR SINDHALAICHERY HAD COME TO OUR HOSPITAL
FOR HAVING RECURRENT SIZURES FOR THE PAST 1 WK H/O PRESENT ILLNESS PT HAD
SEISURE ACTIVITY FROM HER 23rd YEAR ONWARDS PT NOTED TO HAVE GTCS TYPE OF
SIZURES FROM HER 23 YEARS HAD LOCAL TRT AND HAD RECURRENT SEIZURES ATLEAST
ONCE IN 10 YEARS PT HAD MENARCHE AT HER 16 YEARS- IRREGUAR PERIODS-NORMAL
INTELLIGENCE MARRIED AT HER 21 YEARS HAD BECOME PREGNANT AT HER 22 YEARS,
HAD SPONTANEOUS ABORTION AT 3MA2 YEARS LATER SHE BECOME PREGNANT FTND FEMALE
CHILD DIED ON 2ND DAY DEATH WAS ATRIBUTED TO PREMATURE BIRTH
BORN IN A FAMILY AS 2ND CHILD
•
•
ELDER BROTHER DIED AT HIS 45 YEARS ( 3 YEAR BACK)
HE HAS 2 MALE CHILDREN ONE AT 11 HAS RECURRENT LRI ANOTHER ONE AT 8
HAS SPEECH DEFECTS
3 42 YEAR FEMALE 2 CHILDREN ONE HAVING PHOCOMELIA OF LT UL
4 40 YEAR MALE
MR UN MARRIED NEED ASSISTANCE
5 35 YEARS MALE COMMITTED SUICIDE AT HIS 35 YEARS
6. 33 YEARS FEMALE LL POLIO HAS ONE MALE CHILD AT 2 YEARS NOT SPEAKING
Pt IS APPARENTLY NORMAL
WALKS WITH DIFFICULTY (B/L CLUB FOOT)
HT IS 150 CM
NO DEVELOPMENTAL DELAY –HISTORY COULD NOT BE ELICITED PROPERLY
PT IS HAVING WEBBING OF THE NECK
Incomplete folding of ears
PT IS HAVING PECTUS CARINATUM
THORACIC SCLOSIS CONVEXITY FACING THE RT SIDE
B/L CLUB FOOT
NO E/O CRANIAL N PALSIES
HIGHER FUNCTIONS ARE NORMAL
NO SENSORY DISTURBANCES
NO MOT OR DEFICIT
NO ANS DISUTBANCE
VITALS ARE NORMAL
INVESTIGATIONS
HT
150 CM
CBC
NORMAL
USG
NORMAL
ECG
NORMAL
CT BRAIN NORMAL
ECHO
SAV EF 65%
EEG
ABNORMAL WITH B/L PAROXYSMAL DISCHARGES
WITH THIS -A PROBABLE DIAGNOSIS OF NOONAN’S SYNDROME WAS MADE
Approximately 1 in 1,000 and 1 in 2,500 children worldwide
are born with NS.
It is one of the most common genetic syndromes associated with
congenital heart disease, similar in frequency to Down syndrome.
However, the range and severity of features can vary greatly in patients with NS.
Therefore, the syndrome is not always identified at an early age.
Establishing the diagnosis can be very difficult, especially in adulthood.
There is a great variability in expression, and the phenotype becomes less pronounced
with increasing age.
Noonan syndrome (NS) is a relatively common autosomal dominant congenital disorder
that affects both males and females.
It is referred to as the male version of Turner's syndrome
however, the genetic causes of Noonan syndrome and Turner syndrome are distinct.
people with NS have one of the following heart defects:
Pulmonary valvular stenosis (50–60%)
Septal defects: atrial (10–25%) or ventricular (5–20%)
Heart murmur
Hypertrophic cardiomyopathy (12–35%)
Studies show that 30-45 % - CVS NORMAL
Lungs
Restrictive lung function has been reported in some patients
Gastrointestinal system
Failure to thrive From infancy to puberty (75%)
Decreased appetite
Digestive problems
Frequent or forceful vomiting
Swallowing difficulties
Intestinal malrotation
Need for a feeding tube
Low gut motility
Gastroparesis (delayed gastric emptying)
Genito-urinary system
Cryptorchidism (undescended testicles)
Lymphatic system
Posterior cervical hygroma (webbed neck) Lymphedema
Developmental
Intellectual disability
Clumsiness
Motor development delay
Learning disabilities
Dysmaturity
Speech-language pathology
Autism, pervasive developmental disorder
Frequent illnesses, doctor appointments, pain, headaches and fatigue are a few things that
can affect school attendance and performance.
Neuropsychological testing is recommended to find strengths and challenges to tailor
support needed for school, career.
Speech therapy for speech and articulation issues, physical therapy and occupational
therapy for gross and fine motor delays are needed.
Hypotonia and motor difficulties often impact handwriting. Accommodations for
lessening handwriting demands will improve performance and save long term hand function.
Hematologic
Bleeding disorders
Easy bruising
Amegakaryocytic thrombocytopenia (low platelet count)
Blood clotting disorders
Von Willebrand disease
Prolonged activated partial thromboplastin time
Partial deficiency of Factor VIII:C
Partial deficiency of Factor XI:C
Partial deficiency of Factor XII:C
Platelet dysfunction
Combined coagulation defects
Imbalance of Plasminogen Activator Inhibitor Type-1 (PAI-1)
and Tissue Plasminogen Activator (t-PA) Activity.
Musculoskeletal
Joint pain or muscle pain, with differing severity, which varies in severity
Undifferentiated Connective Tissue Disorders with hypermobility
Neurological
Arnold-Chiari malformation (type 1), which can lead to hydrocephalus, has been
noted in some patients Seizures
Stature and posture
Short stature
Cervical (neck) spine fusion
Scoliosis
Prominence of breast bone (pectus carinatum)
Depression of breast bone (pectus excavatum)
Joint contractures or tightness
Joint hypermobility or looseness
Growth retardation
Winging of the scapula
Hypotonia (low muscle tone) and hypermobility syndrome
Lordosis (increased hollow in the back) due to poor stomach muscle tone
Head
Excess skin on the back of the neck
Low hairline at the nape of the neck
High hairline at the front of the head
Large head
Triangular face shape
Broad forehead
Short neck, webbed neck
Curly hair
Eyes
Hypertelorism (widely set eyes) (95%)
Epicanthal folds (extra fold of skin at the inner corner of the eye)
Ptosis (drooping of the eyelids)
Proptosis (bulging eyes)
Refractive visual errors
Strabismus (inward or outward turning of the eyes)
Nystagmus (jerking movement of the eyes)
In some cases, an affected person inherits the mutation from one affected parent. Other cases
result from new mutations in the gene and occur in people with no history of the disorder in
their family.
The principal features include
congenital heart defect (typically pulmonary valve stenosis;
also atrial septal defect and hypertrophic cardiomyopathy),
short stature, learning problems,
pectus excavatum, impaired blood clotting, and a characteristic configuration
of facial features including a webbed neck and a flat nose bridge.
NS is a RASopathy, and
is one of several disorders that are caused by a disruption of RAS-MAPK pathway signaling.
Most cases of Noonan syndrome result from mutations in 1 of 3 genes, PTPN11, SOS1, or
RAF1. PTPN11 gene mutations account for approximately 50% of all cases of Noonan
syndrome.
The cause of Noonan syndrome in the remaining 20% of people with this disorder is
unknown.
Neonatal feeding difficulties and failure to thrive may be seen. Onset of puberty is
delayed by approximately 2 years, and the pubertal growth spurt is often reduced or
absent. The average bone age is also delayed by 2 years.
Mean adult height is 162.5 cm in males and 152.7 cm in females.
Both values are below the 3rd centile.
Characteristic chest deformities consist of pectus carinatum superiorly and pectus
xcavatum inferiorly. These sternal abnormalities are present in 70-95% of cases.
Other common orthopedic features include cubitus valgus (50%), radioulnar synostosis
(2%), clinobrachydactyly (30%), joint hyperextensibility (50%), and talipes equinovarus
(12%).
In both sexes, pubertal development is delayed.
Fertility is not impaired in female patients.
Hearing loss due to otitis media is a frequent complication.
Nose
Small, upturned nose
Ears and hearing
Low-set ears (in over 90%)
Backward-rotated ears (over 90%)
Thick helix (outer rim) of ear(over 90%)
Incomplete folding of ears
Chronic otitis media (ear infections)
Hearing loss
Mouth and speech
Deeply grooved philtrum (top lip line) (over 90%)
Micrognathia (undersized lower jaw)
High arched palate
Dental problems
Articulation difficulties
Poor tongue control
Limbs/extremities
Bluntly ended fingers
Extra padding on fingers and toes
Edema of the back of hands and tops of feet
Cubitus valgus (elbow deformity with abnormal turning-in)
Skin
See also: List of conditions associated with café au lait macules
Lymphedema (lymph swelling of the extremities)
Keloid formation, excessive scar formation
Hyperkeratosis (overdevelopment of outer skin layer)
Pigmented nevi (darkly pigmented skin spots)
Connective tissue disease
DIAGNOSIS
Diagnosis is based on clinical features
In other words, it is made when a physician feels that a patient has enough of the
features to warrant the label indicating association. The patient can be screened for
mutations in the PTPN11, SOS1, or KRAS genes; however, absence of a mutation will
not exclude the diagnosis as there are more as yet undiscovered genes that cause NS.
DIFFERENTIAL DIAGNOSIS
The first to mention is Turner syndrome (45, X0
Cardio-Facio-Cutaneous (CFC) syndrome,
Costello syndrome,
Neurofibromatosis type 1 (NF1),
and LEOPARD syndrome
William's syndrome and
Aarskog syndrome.
GENETIC COUNSELING
Before the child is born, consultations with parents may address the following,
as appropriate:
Explain the mechanisms for occurrence or recurrence of NS in the fetus and the
recurrence risk in the family.
Review the natural history and manifestations of NS, including variability.
Discuss further studies that should be done, particularly those in the newborn period
that will confirm the diagnosis.
If miscarriage, stillbirth, or termination occurs, confirmation of the clinical diagnosis by
autopsy is also important.
Review the currently available treatments and interventions.
Explore the options available to the family for the management and rearing of the child.
ANTENATAL USG
NS should be considered in all fetuses with polyhydramnios, pleural effusions, edema,
and increased nuchal fluid with a normal karyotype.
If there is clinical evidence of NS in the fetus or a first-degree relative has NS,
obstetric ultrasound is indicated at 12-14 and 20 weeks′ gestation and again in the third
trimester.
Fetal echocardiography is indicated at 18-20 weeks′ gestation. If NS is suspected
in the unborn child, physical examination of the parents for features of the syndrome is indicated.
A DNA test for mutation analysis can be carried out on blood, chorionic villi, and amniotic
fluid samples.
Herewith also, pre-implantation genetic diagnosis becomes a possibility.
PROGNOSIS
New medical problems are not expected to appear in adulthood.
However, males who were born with undescended testes
may have fertility problems.
There is no evidence for
gynecological or childbearing complications in females with NS.
THANKYOU
DR. SMT ARASU