NOONAN SYNDROME – CASE REPORT

Abstract

Noonan Syndrome is a rare, autosomal dominant disorder characterized by short stature, facial abnormalities, congenital heart defects and urogenital malformations. Ocular changes occur in 95% of patients and usually include hypertelorism, ptosis, refractive errors, strabismus, amblyopia, rarely nystagmus, colobomas, cataracts, optic nerve drusen. Case report: We present a case of a boy, 10 months old, referred by the pediatrician because of strabismus. During the general examination of the head and face, we noted that the ears were low-set, and the lower jaw was slightly smaller. Ophthalmological examination revealed hypertelorism, left eye esotropia, hyperopia, and optic disc pit. Other associated malformations were: dilatation of both pyelons, cryptorchidism, pulmonary stenosis. Genetic analysis confirmed the diagnosis of Noonan syndrome. The variety of clinical manifestations of this syndrome indicates that a multidisciplinary approach is necessary for diagnosis, treatment, and follow-up of these patients.

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54
Case report UDC: 616-007-053.2-071:617.7
doi:10.5633/amm.2014.0209
NOONAN SYNDROME – CASE REPORT
Milena Vujanović1, Gordana Stanković-Babić1,2, Sonja Cekić1,2
Noonan Syndrome is a rare, autosomal dominant disorder characterized by short
stature, facial abnormalities, congenital heart defects and urogenital malformations.
Ocular changes occur in 95% of patients and usually include hypertelorism, ptosis,
refractive errors, strabismus, amblyopia, rarely nystagmus, colobomas, cataracts, optic
nerve drusen.
Case report: We present a case of a boy, 10 months old, referred by the
pediatrician because of strabismus. During the general examination of the head and
face, we noted that the ears were low-set, and the lower jaw was slightly smaller.
Ophthalmological examination revealed hypertelorism, left eye esotropia, hyperopia, and
optic disc pit. Other associated malformations were: dilatation of both pyelons,
cryptorchidism, pulmonary stenosis. Genetic analysis confirmed the diagnosis of Noonan
syndrome.
The variety of clinical manifestations of this syndrome indicates that a
multidisciplinary approach is necessary for diagnosis, treatment, and follow-up of these
patients. Acta Medica Medianae 2014;53(2):54-56.
Key words: congenital anomalies, ocular manifestations, systemic manifestations
Clinic for Eye Diseases, Clinical Center Niš, Serbia1
Univers ity of Niš Facult y of Medicine, Serbia2
Contact: Milena Vujanović
Clinic for Eye Diseases, Clinical Cente r Niš
Bul. Dr Zorana Đinđića 48, 18000 Niš, Serbia
E-mail: milenavujanovic@gmail.com
Introduction
Noonan Syndrome (NS) is a rare autosomal
dominant inherited disorder. It was known under
various names such as male Turner's syndrome,
Turner-like syndrome or Turner syndrome with
normal karyotype, when in 1963 Dr. Jacqueline
Noonan defined these changes as a specific
syndrome which was named after her (1). The
incidence of NS is different and ranges from 1/1000
to 1/2500 live births (2,3).
The disease is characterized by short statue,
facial abnormalities, congenital heart defects and
urogenital malformations. Less frequently the
disease may be accompanied by delayed psycho-
motor development. Also, in these patients,
especially in childhood, disorders of coagulation
factors (VIII, XI, XII) and thrombocytopenia are
common. The hearing loss may also occur. In a
small percentage of subjects, pigmentation
disorders such as naevi, cafe-au-lait spots and
lentigo occur. It is of great importance to mention
that in these patients, there is a high incidence of
lesions of the eye, usually hypertelorism, down-
slanting palpebral fissures, epicanthic folds, ptosis,
refractive errors, strabismus, amblyopia, nys-
tagmus, and rarely cataract, colobomas, and
keratoconus (4-6).
We present a case of a boy, 10 months old,
sent by the pediatrician because of strabismus.
Ophthalmological examination showed: hyper-
telorism, down-slanting palpebral fissures, left eye
esotropia (angle of deviation 15 Δd). Ocular
motility, as well as convergence, were preserved in
all directions. The child followed a toy and a light
source in all directions (Figure 1). Anterior segment
examination was normal and the value of
intraocular pressure/IOP was 10mmHg. After
performing the indirect ophthalmoscopy (indirect
ophthalmoscope-Heine 500, Germany) we found
that retinal blood vessel network was completely
developed and the bilateral presence of optic disc
pits was diagnosed. During cycloplegia, achieved by
topical administration of Sol. Atropin 0,25%, mild
hypermetropia (+1,0Dsph) was found. Ultrasound
examination of the eyes was performed.
(Ultrasound A/ B Scanner UD-6000, Tomey, A-
scan, 10MHz, 5.3 mm). Axial length (Lax) was
measured on both eyes, 20.95 mm right eye and
OS 20.98 mm left eye. Ultrasound B-scan confirmed
the presence of optic disc pit (Figure 2 and 3).
Visual evoked potential in the right eye was normal,
but on the left it was less defined, with prolonged
latency and lower amplitude.
Figure 1.

Acta Medica Medianae 2014, Vol.53(2) Noonan syndrome – case report
55
Table 1. Scoring system for diagnosis of NS
Present changes
A=major
B=minor
Face
Typical face dysmorphology
Suggestive face dysmorphology
Heart
Pulmonary valve stenosis,
cardiomiopathy
Other defect
Body height
<P3*
<P10*
Thorax
Pectus carinatun/excavatum
Broad thorax
Family history First degree relative with definite NS
First degree relative with suggestive
NS
Other
Mental retardation, cryptorchidism
and lymphatic dysplasia
Milder forms of these changes
* P3 and P10-related measures height by age (normal range P3-P97)
Definitive NS: 1 "A" plus other major sign or two minor signs; 1 "B" plus two major signs or three minor signs
Figure 2. Eho OD (Ultrasound A / B Scanner UD-6000,
Tomey, A-scan, 10MHz, 5.3 mm)
Figure 3. Eho OS (Ultrasound A / B Scanner UD-6000,
Tomey, A-scan, 10MHz, 5.3 mm)
General examination of the head and neck
showed that the ears were low-set, irregularly
shaped, posteriorly rotated, with a thick helix, high
arched palate, micrognathia.
From the child’s medical documentation on
the previous treatment we found out that it was a
premature child (GS 36 weeks, TM 2500g) which
suffered from respiratory distress syndrome,
intracranial hemorrhage of the first degree,
dilatation of both renal pyelons, migratory testis,
and stenosis a. pulmonalis. Because of hypotonia,
the child was prescribed an adequate physical
treatment by a physiatrist.
However, due to all these changes, the child
was referred to a geneticist. A normal male
karyotype type (46 XY) was determined, but the
clinical examination of the child pointed to Noonan
syndrome. Genetic testing of the child and parents
confirmed PTPN11 gene mutation on chromosome
12.
Discussion
Syndrome Noonan includes a very hetero-
geneous group of multiple congenital anomalies,
which are easy to recognize clinically. However,
due to a various degree of manifestations of
these changes, a scoring system was created to
help the diagnostic process (Table 1) (7).
This scoring system is very important for
early recognition of this syndrome and appro-
priate treatment of numerous anomalies.
As the child grows, the clinical diagnosis is
more and more difficult as the changes are not
easily noticed, and the risk of consequences of
untreated anomalies such as cardiac anomaly,
cryptorchidism, chest wall deformities, coagulation
disorders, slow psychomotor development, strabi-
smus and amblyopic increase during the growth.
The ocular abnormalities in Noonan syn-
drome are very common and are found in about
95% of cases (6,8). The most common are
refractive errors (61%), strabismus (48-63%),
and amblyopia (33%) (5,8). Coloboma and other
malformations of the retina occur very rarely
(10%) and are usually associated with PTPN11
gene mutations (8,9). Given such a high inci-
dence of ocular changes, the ophthalmologist can
be a very important link in the diagnostic chain,
as was the case with the patient we presented.
Even though the diagnosis of Noonan
syndrome can be established on the basis of the
clinical picture, it is important to do genetic
testing whenever possible. In approximately 50%
of these patients there is a mutation of PTPN11
gene on chromosome 12. This gene is respon-
sible for the synthesis of the enzyme tyrosine
phosphatase SHP-2. It is an intracellular signal
for initiating a cascade reaction growth factor
receptor, cytokines and hormones that regulate
the processes of growth and development (10,11).
Noonan syndrome mostly occurs on a sporadic

Noonan syndrome – case report Milena Vujanović et al.
56 This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) Licence
basis or in a pattern consistent with autosomal
dominant inheritance, with a predominance of
maternal transmission (11,12). De novo mutation
of PTPN11 is possible in sporadic cases of Noonan
syndrome and is predominantly of paternal
origin, as was the case in the present patient.
However, there is evidence for a rare autosomal
recessive form of the disease (12).
Conclusion
This rare syndrome is characterized by a
very heterogeneous group of changes in various
organs, which further requires a multidisciplinary
approach in order to provide early diagnosis and
treatment of numerous malformations in these
patients.
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SYNDROMA NOONAN – PRIKAZ BOLESNIKA
Milena Vujanović, Gordana Stanković-Babić, Sonja Cekić
Nunanov sindrom je retka autozomalno dominantno nasledna bolest, koja se
karakteriše niskim rastom, abnormalnostima lica, urođenim promenama na srcu i
urogenitalnom traktu. Promene na oku javljaju se kod 95% ovih bolesnika i najčešće su to
hipertelorizam, ptoza, refrakcione anomalije, strabizam, ambliopija, ređe nistagmus,
kolobomi, katarakta, druze papile vidnog živca.
Prikazujemo slučaj dečaka starog 10 meseci, upućenog od strane pedijatra zbog
skretanja levog oka. Opštim pregledom glave i lica primećeno je da su uši niže postavljene,
a donja vilica nešto manja. Oftalmološkim pregledom nađen je hipertelorizam, esotropija
levog oka, hipermetropija, anomalija optičkog diska po tipu jamice. Pregledom
dokumentacije deteta saznajemo da se radi o prevremeno rođenom detetu, koje je imalo
respiratorni distres sindrom, intrakranijalne hemoragije, dilataciju oba pijelona, migratorni
testis, stenozu a.pulmonalis. Konsultativnim pregledom genetičara potvrđena je dijagnoza
sindroma Noonan.
Raznolikost kliničkih manifestacija ovog sindroma ukazuje na neophodnost
multidisciplinarnog pristupa kako u otkrivanju tako i u kasnijem lečenju i praćenju ovih
bolesnika. Acta Medica Medianae 2014;53(2):54-56.
Ključne reči: kongenitalne anomalije, očne manifestacije, sistemske manifestacije