Shaina Mavreen D. Villaroza
1. Wolf-Hirschhorn Syndrome:
Wolf–Hirschhorn syndrome (WHS), also known
as chromosome deletion Dillan 4p syndrome, Pitt-Rogers-Danks
syndrome (PRDS) or Pitt syndrome, was first described in 1961 by
Americans Herbert L. Cooper and Kurt Hirschhorn and, thereafter,
gained worldwide attention by publications by the German Ulrich
Wolf, and Hirschhorn and their co-workers, specifically their articles
in the German scientific magazine Humangenetik. It is a
characteristic phenotype resulting from a partial deletion of
chromosomal material of the short arm of chromosome 4.
The signs and symptoms of Wolf-Hirschhorn are related to
the loss of multiple genes on the short arm of chromosome 4.
WHSC1, LETM1, and MSX1 are the genes that are deleted in people
with the typical signs and symptoms of this disorder. These genes
play significant roles in early development, although many of their specific functions are
unknown. Researchers believe that loss of the WHSC1 gene is associated with many of the
characteristic features of Wolf-Hirschhorn syndrome, including the distinctive facial
appearance and developmental delay. Deletion of the LETM1 gene appears to be associated
with seizures or other abnormal electrical activity in the brain. A loss of the MSX1 gene may
be responsible for the dental abnormalities and cleft lip and/or palate that are often seen
with this condition.
2. Jacobsen Syndrome
Jacobsen Syndrome, also known as 11q deletion
disorder, is a rare congenital disorder resulting from
deletion of a terminal region of chromosome 11 that
includes band 11q24.1. It can cause intellectual
disabilities, a distinctive facial appearance, and a
variety of physical problems including heart defects and
a bleeding disorder. The syndrome was first identified
by Danish physician Petra Jacobsen, and is believed to
occur in approximately 1 out of every 100,000 births.
Other features of Jacobsen syndrome can
include heart defects, feeding difficulties in infancy,
short stature, frequent ear and sinus infections, and
skeletal abnormalities. The disorder can also affect the digestive system, kidneys, and
genitalia. The life expectancy of people with Jacobsen syndrome is unknown, although
affected individuals have lived into adulthood.
3. Cri-du-chat Syndrome
Cri du chat syndrome, also known as
chromosome 5p deletion syndrome, 5p minus
syndrome or Lejeune’s syndrome is a rare genetic
disorder due to a missing part of chromosome 5. Its
name is a French term (cat-cry or call of the cat)
referring to the characteristic cat-like cry of affected
children. It was first described by Jérôme Lejeune in
1963. The condition affects an estimated 1 in 50,000
live births, strikes all ethnicities, and is more common
in females by a 4:3 ratio.
The syndrome gets its name from the
characteristic cry of affected infants, which is similar
to that of a meowing kitten, due to problems with the
larynx and nervous system. About 1/3 of children lose
the cry by age 2. Other symptoms of cri du chat
syndrome may include:
feeding problems because of difficulty
swallowing and sucking.
low birth weight and poor growth.
severe cognitive, speech, and motor delays.
behavioral problems such as hyperactivity, aggression, tantrums, and
unusual facial features which may change over time.
4. Rett Syndrome
Rett syndrome is a neurological and developmental disorder that mostly occurs in
females. Infants with Rett syndrome seem to grow and develop normally at first, but then
stop developing and even lose skills and abilities.
For instance, they stop talking even though they used to say certain words. They
lose their ability to walk properly. They stop using their hands to do things and often
develop stereotyped hand movements, such as wringing, clapping, or patting their hands.
Rett syndrome is considered one of the autism spectrum disorders. Most cases of Rett
syndrome are caused by a mutation on the MECP2 gene, which is found on the X
Some argue that it is misclassified as an autism spectrum disorder, just as it would
be to include such disorders as fragile X syndrome, tuberous sclerosis, or Down syndrome
where one can see autistic features. However, it has been suggested that it be removed from
the DSM-5, because it has a specific etiology.
It has also been argued that Rett Syndrome is in fact a neurodegenerative condition
as opposed to a neurodevelopmental condition. This was shown by the fact that mice with
induced Rett Syndrome can have their neurons completely restored and a normal phenotype
by adding the MECP2 gene back to their genome. This information has also helped lead to
further studies in curing or treating the disorder.
It was first described by Austrian pediatrician Andreas Rett in 1966.
5. Duchene Muscular Dystrophy
Duchenne muscular dystrophy (DMD) is a
recessive X-linked form of muscular dystrophy,
affecting around 1 in 3,600 boys, which results in
muscle degeneration and eventual death. The disorder
is caused by a mutation in the dystrophin gene, located
on the human X chromosome, which codes for the
protein dystrophin, an important structural component
within muscle tissue that provides structural stability
to the dystroglycan complex (DGC) of the cell
membrane. While both sexes can carry the mutation,
females rarely exhibit signs of the disease.
Symptoms usually appear in male children
before age 5 and may be visible in early infancy. Even
though symptoms do not appear until early infancy, there is laboratory evidence, which can
distinguish a child with the disease at birth. Progressive proximal muscle weakness of the
legs and pelvis associated with a loss of muscle mass is observed first. Eventually this
weakness spreads to the arms, neck, and other areas. Early signs may include
pseudohypertrophy (enlargement of calf and deltoid muscles), low endurance, and difficulties
in standing unaided or inability to ascend staircases. As the condition progresses, muscle
tissue experiences wasting and is eventually replaced by fat and fibrotic tissue (fibrosis). By
age 10, braces may be required to aid in walking but most patients are wheelchair dependent
by age 12. Later symptoms may include abnormal bone development that lead to skeletal
deformities, including curvature of the spine. Due to progressive deterioration of muscle, loss
of movement occurs, eventually leading to paralysis. Intellectual impairment may or may not
be present but if present, does not progressively worsen as the child ages. The average life
expectancy for patients afflicted with DMD is around 25.
6. Charcot-Marie-Tooth Disease Type IA
The most common cause of CMT (70-80% of the
cases) is the duplication of a large region in
chromosome 17p12 that includes the gene PMP22.
Some mutations affect the gene MFN2, which codes for
a mitochondrial protein. Cells contain separate sets of
genes in their nucleus and in their mitochondria. In
nerve cells, the mitochondria travel down the long
axons. In some forms of CMT, mutated MFN2 causes
the mitochondria to form large clusters, or clots, which
are unable to travel down the axon towards the
synapses. This prevents the synapses from functioning.
Type 1 Charcot-Marie-Tooth disease is characterized by abnormalities in myelin, the
protective substance that covers nerve cells. Type 2 Charcot-Marie-Tooth disease is
characterized by abnormalities in the fiber, or axon, that extends from a nerve cell and
transmits nerve impulses. Type 4 Charcot-Marie-Tooth disease affects either the axon or
myelin and is distinguished by its pattern of inheritance. In intermediate forms of Charcot-
Marie-Tooth disease, abnormalities occur in both axons and myelin. Type X Charcot-Marie-
Tooth disease is caused by mutations in a gene on the X chromosome, one of the two sex
chromosomes. Within the various types of Charcot-Marie-Tooth disease, subtypes (such as
1A, 2A, 4A, and X1) are distinguished by the specific gene that is altered.
Charcot-Marie-Tooth disease is a group of progressive disorders that affect the
peripheral nerves and result in problems with movement and sensation. Peripheral nerves
connect the brain and spinal cord to muscles and to sensory cells that detect sensations such
as touch, pain, heat, and sound.
7. Edwards Syndrome
Edwards syndrome (also known as Trisomy 18 (T18) or Trisomy
E) is a genetic disorder caused by the presence of all or part of an
extra 18th chromosome. This genetic condition almost always results
from nondisjunction during meiosis. It is named after John H. Edwards,
who first described the syndrome in 1960. It is the second most common
autosomal trisomy after Down syndrome that carries to term.
Affected individuals may have heart defects and abnormalities
of other organs that develop before birth. Other features of trisomy 18
include a small, abnormally shaped head; a small jaw and mouth; and
clenched fists with overlapping fingers.
Edwards syndrome occurs in around one in 6,000
live births and around 80 percent of those affected are
female. The majority of fetuses with the syndrome die
before birth. The incidence increases as the mother's age
increases. The syndrome has a very low rate of survival,
resulting from heart abnormalities, kidney malformations,
and other internal organ disorders.
8. Patau Syndrome
Patau syndrome is a syndrome caused by a chromosomal abnormality, in which some
or all of the cells of the body contain extra genetic material from chromosome 13. This can
occur either because each cell contains a full extra copy of chromosome 13 (a disorder known
as trisomy 13 or trisomy D), or because each cell contains an extra partial copy of the
chromosome (i.e., Robertsonian translocation) or because of mosaic Patau syndrome. Full
trisomy 13 is caused by nondisjunction of chromosomes during meiosis (the mosaic form is
caused by nondisjunction during mitosis). In Patau syndrome, the extra genetic material
from chromosome 13 disrupts the normal course of development, causing severe heart and
kidney defects, amongst other features characteristic of Patau syndrome. Like all
nondisjunction conditions (such as Down syndrome and Edwards syndrome), the risk of this
syndrome in the offspring increases with maternal age at pregnancy, with about 31 years
being the average. Patau syndrome affects somewhere between 1 in 10,000 and 1 in 21,700
Newborns with Patau syndrome share common physical characteristics:
Extra fingers or toes (polydactyly)
Deformed feet, known as rocker-bottom feet
Neurological problems such as small head (microcephaly), failure of the brain
to divide into halves during gestation (holoprosencephaly), severe mental
Facial defects such as small eyes (microphthalmia), absent or malformed
nose, cleft lip and/or cleft palate
Heart defects (80% of individuals)
9. Down Syndrome
Down syndrome (DS) or Down's syndrome, also
known as trisomy 21, is a chromosomal condition caused
by the presence of all or part of a third copy of chromosome
21. Down syndrome is the most common chromosome
abnormality in humans. It is typically associated with a
delay in cognitive ability (mental retardation, or MR) and
physical growth, and a particular set of facial
characteristics. The average IQ of young adults with Down
syndrome is around 50, compared to children without the
condition with an IQ of 100. A large proportion of
individuals with Down syndrome have a severe degree of
The physical features and medical problems
associated with Down syndrome can vary widely
from child to child. While some kids with DS need a
lot of medical attention, others lead healthy lives.
Down syndrome is named after John
Langdon Down, the British physician who
described the syndrome in 1866.
Philadelphia chromosome or Philadelphia
translocation is a specific chromosomal abnormality that is
associated with chronic myelogenous leukemia (CML). It is the result of a reciprocal
translocation between chromosome 9 and 22, and is specifically designated t(9;22)(q34;q11).
The presence of this translocation is a highly sensitive test for CML, since 95% of people with
CML have this abnormality (the remainder has either a cryptic translocation that is invisible
on G-banded chromosome preparations, or a variant translocation involving another
chromosome or chromosomes as well as the long arm of chromosomes 9 and 22). However,
the presence of the Philadelphia (Ph) chromosome is not sufficiently specific to diagnose
CML, since it is also found in acute lymphoblastic leukemia (ALL, 25–30% in adult and 2–
10% in pediatric cases) and occasionally in acute myelogenous leukemia (AML).
National Institutes of Health, Eunice Kennedy Shriver,
National Institute of Child Health & Human Development