A.

Noonan Syndrom
1. Genetic Mechanism
Noonan syndrome is an autosomal dominant, variably expressed, multisystem disorder
with an estimated prevalence of 1 in 1000–2500. It was characterised by Jacqueline Noonan,
who reported nine patients with pulmonary valve stenosis, small stature, hypertelorism, mild
intellectual disability, ptosis, undescended testes, and skeletal malformations.
The RAS–MAPK pathway is a well-studied, widely important signal transduction pathway
through which extracellular ligands—such as some growth factors, cytokines, and hormones
stimulate cell proliferation, differentiation, survival, and metabolism. Cell surface receptors
are phosphorylated at sites within their cytoplasmic region after ligand binding. This binding
leads to recruitment of adaptor proteins (eg, GRB2), which form a constitutive complex with
guanine nucleotide exchange factors (eg, SOS) that convert inactive, GDP-bound RAS to its
active GTP-bound form. Activated RAS proteins then activate the RAF–MEK–ERK cascade
through a series of phosphorylation events, ending with activated ERK entering the nucleus
to alter gene transcription and modulating the activity of cytoplasmic targets to cause the
appropriate short-term and long-term cellular response to the stimulus. All the genes
implicated in Noonan syndrome encode proteins integral to this pathway and disease-causing
mutations usually enhance signal flow through this pathway.
2. Symptom
Many of the recognisable features of Noonan syndrome could be the consequence of
lymphatic obstruction or dysfunction during development, including webbing of the neck and
prominence of the trapezius, cryptorchidism, widely spaced nipples, low-set and posteriorly
rotated ears, hypertelorism, and ptosis. Other key features of Noonan syndrome include
congenital heart defects, superior pectus carinatum with inferior pectus excavatum,
developmental delay, short stature, and lymphatic dysplasias.
Sumber :
Roberts, A., Allanson, J., Tartaglia, M. and Gelb, B. (2013). Noonan Syndrome. NIH Public Accesss,
381(9863), pp.333-342.

B. Klippel Feil Syndrom

1. Genetic Mechanism
Klippel-Feil Syndrome (KFS) is defined as congenital fusion of two or more cervical vertebrae,
results from faulty segmentation along the embryo’s developing axis during 3-8 weeks of
gestation with incidence of 1:40000 to 1:42000 births. KFS, or synostosis of the cervical spine,
occurs as a result of failure in normal segmentation of cervical mesodermal somites during
embryonic development. This failure occurs at second-eight weeks of gestation and its cause
is unknown. The most common signs are short neck, low posterior hairline and restricted
mobility of upper spine. Associated abnormalities may include scoliosis or kyphosis,
Sprengel’s deformity, hemivertebrae, platybasia, basilar impression, spina bifida, anomalies of
the kidneys and the ribs, cleft palate, respiratory problems, deafness or hearing impairment,
and heart malformations.
2. Symptom
Most patients who have this syndrome are first seen with restricted motion of the neck,
torticollis, webbing of the neck, or Sprengel deformity. Webbed Neck as well as the rare in
Klippel-Feil syndrome.
 Sumber :

Patel, M., Gupta, R., Bajaj, N. and Tagore, V. (2014). Klippel-Feil syndrome: a case report.
International Journal of Research in Medical Sciences, 2(3), p.1199.

Hikade KR, Bitar GJ, Edgerton MT, Morgan RF (2002). Modified Z-plasty repair of webbed
neck deformity seen in Turner and Klippel-Feil syndrome. Cleft Palate Craniofac. J. 39 (3):
261–6.

C. Diamond-Blackfan Anemia Syndrom

1. Genetic Mechanism
Diamond-Blackfan anemia is caused by mutations in several genes, some of which have
been identified and some of which have not. Identified genes include but are not limited to:
RPS19, RPL5, RPS10, RPL11, RPL35A, RPS7, RPS17, RPS24, RPS26 and GATA1 genes.
Different subtypes exist and are divided based on the specific gene mutated; however, they
have similar features. Patients with mutations in the RPL5 gene have more serious symptoms
and about 45% have cleft palate and are smaller than average size. Patients with mutations in
the RPL11 gene have thumb anomalies more frequently than people with the other types.
Mutations in the GATA1 gene are associated with severe anemia. Most cases are isolated, but
about 45% of people with Diamond-Blackfan anemia inherit this condition from a parent.
Inheritance is typically autosomal dominant , but can rarely be X-linked.
2. Symptom
Approximately people with Diamond Blackfan Anemia Syndrom, 80%-99% have symptoms
in Abnormal Heart rate, Arrhythmia, Macrocytic Anemia, Migraine, Acute Leukemia, and
Webbed Neck is very rare occur in Diamond-Blackfan Anemia Syndrom.

Sumber :
Clinton, C & Gazda, HT. Diamond Blackfan Anemia. GeneReviews. 2014;
http://www.ncbi.nlm.nih.gov/books/NBK7047/.
Diamond-Blackfan Anemia. Online Mendelian Inheritance in Man (OMIM). 2017;
http://omim.org/entry/105650.
Genetics Home. "Diamond-Blackfan anemia". Genetics Home Reference. Retrieved 2017-06