Lardel Kent D.

Caray T01
Cytogenetics BIO 111
Why is the Chromosome the considered to be the basis for heredity?

The speculation that chromosomes might be the key to understanding heredity led several
scientists to examine Mendel's publications and re-evaluate his model in terms of the behavior of
chromosomes during mitosis and meiosis. In 1902, Theodor Boveri observed that proper
embryonic development of sea urchins does not occur unless chromosomes are present. That
same year, Walter Sutton observed the separation of chromosomes into daughter cells during
meiosis. Together, these observations led to the development of the Chromosomal Theory of
Inheritance, which identified chromosomes as the genetic material responsible for Mendelian
inheritance.
The Chromosomal Theory of Inheritance was consistent with Mendel's laws and was
supported by the following observations: During meiosis, homologous chromosome pairs
migrate as discrete structures that are independent of other chromosome pairs. The sorting of
chromosomes from each homologous pair into pre-gametes appears to be random. Each parent
synthesizes gametes that contain only half of their chromosomal complement. Even though male
and female gametes (sperm and egg) differ in size and morphology, they have the same number
of chromosomes, suggesting equal genetic contributions from each parent. The gametic
chromosomes combine during fertilization to produce offspring with the same chromosome
number as their parents.
The machinery of inheritance lies mainly in the nucleus or more particularly the
chromosomes of the cells which form the gametes. The chromosomes in fact are the only entities
that are always passed on in equal quantities from parents to offspring, during sexual
reproduction. The rediscovery of Mendelism in 1900 and the subsequent developments in the
field of genetics, very clearly established the importance of chromosomes in the inheritance of
characters.
 10 Human Genetic Disorders Associated to Chromosome

1. Trisomy 13 (Patau Syndrome)

Trisomy 13, also called Patau syndrome, is a
chromosomal condition associated with severe
intellectual disability and physical abnormalities in
many parts of the body. Individuals with trisomy 13
often have heart defects, brain or spinal cord
abnormalities, very small or poorly developed eyes
(microphthalmia), extra fingers or toes, an opening
in the lip (a cleft lip) with or without an opening in
the roof of the mouth (a cleft palate), and weak
muscle tone (hypotonia).
Most cases of trisomy 13 result from having
three copies of chromosome 13 in each cell in the
body instead of the usual two copies. The extra
genetic material disrupts the normal course of development, causing the characteristic features of
trisomy 13. Trisomy 13 can also occur when part of chromosome 13 becomes attached
(translocated) to another chromosome during the formation of reproductive cells (eggs and
sperm) or very early in fetal development. Affected people have two normal copies of
chromosome 13, plus an extra copy of chromosome 13 attached to another chromosome. In rare
cases, only part of chromosome 13 is present in three copies.
Common abnormalities of this condition include Intellectual disability and motor disorder;
microcephaly, polydactyly; structural eye defects, including microphthalmia, Peters' anomaly,
cataract, iris and/or fundus (coloboma) and retinal dysplasia.
Most cases of trisomy 13 are not inherited and result from random events during the
formation of eggs and sperm in healthy parents. An error in cell division called nondisjunction
results in a reproductive cell with an abnormal number of chromosomes. Trisomy 13 occurs in
about 1 in 16,000 newborns. Although women of any age can have a child with trisomy 13, the
chance of having a child with this condition increases as a woman gets older.
Medical management of children with Trisomy 13 is planned on a case-by-case basis and
depends on the individual circumstances of the patient. Treatment of Patau syndrome focuses on
the particular physical problems with which each child is born. Many infants have difficulty
surviving the first few days or weeks due to severe neurological problems or complex heart
defects.
References:
Chen M, Yeh GP, Shih JC, Wang BT. Trisomy 13 mosaicism: study of serial cytogenetic changes
in a case from early pregnancy to infancy. Prenat Diagn. 2004 Feb;24(2):137-43. Review
Crider KS, Olney RS, Cragan JD. Trisomies 13 and 18: population prevalences, characteristics,
and prenatal diagnosis, metropolitan Atlanta, 1994-2003. Am J Med Genet A. 2008 Apr
1;146A(7):820-6. doi: 10.1002/ajmg.a.32200.
Hall HE, Chan ER, Collins A, Judis L, Shirley S, Surti U, Hoffner L, Cockwell AE, Jacobs PA,
Hassold TJ. The origin of trisomy 13. Am J Med Genet A. 2007 Oct 1;143A(19):2242-8
Janvier, Annie; Farlow, Wilfond (August 1, 2012). "The experience of families with children
with trisomy 13 and 18 in social networks". Pediatrics. 130 (2): 293298.
Parker MJ, Budd JL, Draper ES, Young ID. Trisomy 13 and trisomy 18 in a defined population:
epidemiological, genetic and prenatal observations. Prenat Diagn. 2003 Oct;23(10):856-60.
 2. Trisomy 18 (Edwards syndrome)
Edwards' syndrome (trisomy 18) is a common
autosomal chromosomal disorder due to the
presence of an extra chromosome 18.
Most cases of trisomy 18 result from having
three copies of chromosome 18 in each cell in the
body instead of the usual two copies. The extra
genetic material disrupts the normal course of
development, causing the characteristic features of
trisomy 18.
Approximately 5 percent of people with trisomy
18 have an extra copy of chromosome 18 in only
some of the body's cells. In these people, the
condition is called mosaic trisomy 18. The severity of mosaic trisomy 18 depends on the type
and number of cells that have the extra chromosome. The development of individuals with this
form of trisomy 18 may range from normal to severely affected.
Some feature of individuals having the disease include growth restriction, polyhydramnios,
strawberry-shaped cranium, choroid plexus cyst, overlapping of hands fingers (2nd and 5th on
3rd and 4th respectively),congenital heart defects, omphalocele, single umbilical artery.
Currently, most cases in the developed world are diagnosed antenatally based on screening by
maternal age, maternal serum marker screening, or detection of sonographic abnormalities
during second or third trimester. Antenatal diagnosis of trisomy 18 leads to termination of
pregnancy in 86% of cases.
There are ethical issues surrounding the care and management of infants and children with
Edwards' syndrome. There is some agreement that management decisions should focus on the
best interest of the child and pay due respect to parental opinion. A collaborative approach with
openness among team members is recommended and guidelines for management in the neonatal
unit have been proposed. Treatment of a liveborn infant is generally supportive but life-
sustaining measures are not always carried out. Considerable thought and discussion are
recommended before undertaking measures such as surgical correction of abnormalities. Ideally
a full informed discussion with parents, undertaken before the birth of the child, should inform
management.
Trisomy 18 occurs in about 1 in 5,000 live-born infants; it is more common in pregnancy,
but many affected fetuses do not survive to term. Although women of all ages can have a child
with trisomy 18, the chance of having a child with this condition increases as a woman gets
older.
References:
Bruns DA; Caring for an infant with trisomy 18: A case study and guidelines, Clinical Nursing
Studies
Chen CP, Chern SR, Tsai FJ, Lin CY, Lin YH, Wang W. A comparison of maternal age, sex ratio
and associated major anomalies among fetal trisomy 18 cases with different cell division of error.
Prenat Diagn. 2005 Apr;25(4):327-30.
Cho RC, Chu P, Smith-Bindman R; Second trimester prenatal ultrasound for the detection of
pregnancies at increased risk of Trisomy 18 based on serum screening. Prenat Diagn. 2009
Feb;29(2):129-39. doi: 10.1002/pd.2166.
Irving C, Richmond S, Wren C, et al; Changes in fetal prevalence and outcome for trisomies 13
and 18: a population-based study over 23 years. J Matern Fetal Neonatal Med. 2011
Jan;24(1):137-41. doi: 10.3109/14767051003758879. Epub 2010 Apr 12.
Pont SJ, Robbins JM, Bird TM, Gibson JB, Cleves MA, Tilford JM, Aitken ME. Congenital
malformations among liveborn infants with trisomies 18 and 13. Am J Med Genet A. 2006 Aug
15;140(16):1749-56.
Ramesh KH, Verma RS. Parental origin of the extra chromosome 18 in Edwards syndrome. Ann
Genet. 1996;39(2):110-2
Yeo L, Guzman ER, Day-Salvatore D, Walters C, Chavez D, Vintzileos AM. Prenatal detection
of fetal trisomy 18 through abnormal sonographic features. J Ultrasound Med. 2003
Jun;22(6):581-90; quiz 591-2.
 3. Cri du chat Syndrome (Cats cry)

Cri du chat syndrome (CdCS or 5p-) is a rare genetic

disorder in which a variable portion of the short arm of
chromosome 5 is missing or deleted (monosomic).
Symptoms vary greatly from case to case depending upon
the exact size and location of the deleted genetic material.
Common symptoms include a distinctive cry that
resembles the mewing of a cat, characteristic facial
features, slow growth, and microcephaly, a
condition that indicates that head circumference is
smaller than would be expected for an
infant's age and sex. Affected children also exhibit delays in the acquisition of skills requiring the
coordination of muscular and mental activities (psychomotor disability) and moderate to severe
intellectual disability.
Cri-du-chat syndrome is caused by a deletion of the end of the short (p) arm of chromosome
5. This chromosomal change is written as 5p-. The size of the deletion varies among affected
individuals; studies suggest that larger deletions tend to result in more severe intellectual
disability and developmental delay than smaller deletions. The signs and symptoms of cri-du-
chat syndrome are probably related to the loss of multiple genes on the short arm of chromosome
5. Researchers believe that the loss of a specific gene, CTNND2, is associated with severe
intellectual disability in some people with this condition.
About 10 percent of people with cri-du-chat syndrome inherit the chromosome abnormality
from an unaffected parent. In these cases, the parent carries a chromosomal rearrangement called
a balanced translocation, in which no genetic material is gained or lost. Balanced translocations
usually do not cause any health problems; however, they can become unbalanced as they are
passed to the next generation. Cri-du-chat syndrome occurs in an estimated 1 in 20,000 to 50,000
newborns. This condition is found in people of all ethnic backgrounds.
References:
Cerruti Mainardi P. Cri du Chat syndrome. Orphanet J Rare Dis. 2006 Sep 5;1:33.

Mainardi PC, Pastore G, Castronovo C, Godi M, Guala A, Tamiazzo S, Provera S, Pierluigi M, Bricarelli FD. The
natural history of Cri du Chat Syndrome. A report from the Italian Register. Eur J Med Genet. 2006 Sep-
Oct;49(5):363-83. Epub 2006 Jan 13

Rodrguez-Caballero A, Torres-Lagares D, Rodrguez-Prez A, Serrera-Figallo MA, Hernndez-Guisado JM,

Machuca-Portillo G. Cri du chat syndrome: a critical review. Med Oral Patol Oral Cir Bucal. 2010 May
1;15(3):e473-8. Review

Wu Q, Niebuhr E, Yang H, Hansen L. Determination of the 'critical region' for cat-like cry of Cri-du-chat syndrome
and analysis of candidate genes by quantitative PCR. Eur J Hum Genet. 2005 Apr;13(4):475-85.
 4. Down Syndrome (Trisomy 21)
Down syndrome is a chromosomal condition which is commonly
associated with a characteristic appearance, an intellectual disability
and a weak muscle tone in infancy.
Genetically, Down syndrome results from trisomy 21 in which
the each body cell has three copies of chromosome 21 instead
of the usual two copies. This condition is mostly not inherited
but by a random event during the formation of reproductive cells in
a parent. Those affected individual may not have an
unaffected parent. The parent carries a rearrangement of genetic
material between chromosome 21 and another chromosome. This
rearrangement is called a balanced translocation. No genetic
material is gained or lost in a balanced translocation, so these
chromosomal changes usually do not cause any health problems. However, as this translocation
is passed to the next generation, it can become unbalanced. People who inherit an unbalanced
translocation involving chromosome 21 may have extra genetic material from chromosome 21,
which causes Down syndrome.
There are many features and symptoms of Down syndrome. Physically people with the
condition is characterize by a short height, low muscle tone, short neck, and stocky arms and
legs. They also have slanted eyes, small ears and an irregularly shaped mouth and tongue. With
regards to health, individuals often have intellectual disability, heart defects, hyperthyroidism
and behavioral problems.
Treatment for Down syndrome focuses on making sure that the affected child or individual
has a regular medical checkup, helping him/her develop and master skills, and watching some
early signs of health problems.
References:
Antonarakis SE, Lyle R, Dermitzakis ET, Reymond A, Deutsch S. Chromosome 21 and down
syndrome: from genomics to pathophysiology. Nat Rev Genet. 2004 Oct;5(10):725-38
Cohen WI. Current dilemmas in Down syndrome clinical care: celiac disease, thyroid disorders,
and atlanto-axial instability. Am J Med Genet C Semin Med Genet. 2006 Aug 15;142C(3):141-8
Steingass KJ, Chicoine B, McGuire D, Roizen NJ. Developmental disabilities grown up: Down
syndrome. J Dev Behav Pediatr. 2011 Sep;32(7):548-58. doi: 10.1097/DBP.0b013e31822182e0.
Bull MJ, et al. (2011). Health supervision for children with down syndrome. Pediatrics, 128(2):
398-406. Retrieved from webmd.com

5. Turner Syndrome (45X0)

Turner syndrome is a condition associated with a chromosomal aberration which
affect the females. Specifically and more commonly, this is a result of a lack of an X
 chromosome in females, called
monosomy X from the usual two X
chromosomes in females. The
condition can also occur if one of the
sex chromosomes is partially
missing or rearranged rather than
completely absent. Some women
with Turner syndrome have a
chromosomal change in only some
of their cells, which is known as
mosaicism.
About 1 in 2,500 newborn girls worldwide,
are affected by Turners syndrome but it is
much more common among pregnancies that do not survive to term like miscarriages and
stillbirths. Individuals with this condition have a short stature and non-functioning ovaries which
causes infertility while some women may also have extra skin on the neck (webbed neck),
puffiness or swelling (lymphedema) of the hands and feet, skeletal abnormalities, heart defects,
high blood pressure, and kidney problems.
Most people with Turner's syndrome have normal intelligence and approximately 10 percent
of patients, regardless of the karyotype, will have considerable developmental delays, need
special education, and require ongoing assistance in his/her adult life. Turner syndrome may be
diagnosed before birth or shortly after birth or during early childhood. However, in some cases,
the disorder may not be diagnosed until well into adulthood, often as an incidental finding.
During their adolescent life, the affected individuals experience anxiety, social isolation and
sometimes immaturity. Patients with Turner's syndrome appear to have a decreased life
expectancy, primarily as a result of complications of heart disease and diabetes.
References:
Bondy CA. New issues in the diagnosis and management of Turner syndrome. Rev Endocr
Metab Disord. 2005 Dec;6(4):269-80
Daniel MS. Turner Syndrome. (2015). Medscape Reference:
http://emedicine.medscape.com/article/949681-overview.
Sybert VP, McCauley E. (2004) Turner's syndrome. N Engl J Med. Sep 16;351(12):1227-38.
Toft D, Rehan K. (2014). Turner Syndrome Complications. Retrieved from
https://www.endocrineweb.com/conditions/turner-syndrome/turner-syndrome-complicationns
Ostberg JE, Conway GS. Adulthood in women with Turner syndrome. Horm Res.
2003;59(5):211-21. Review
6. Klinefelters Syndrome
 Another condition affecting males is the Klinefelters
syndrome. This is often called the XXY Condition since it
affects the XY chromosome of the males. Klinefelters
syndrome affects the males physical appearance as well as its
cognitive development. However, its signs and symptoms
may vary from one individual to the other.
People typically have two sex chromosomes in each cell
with females having two X chromosomes while males have
one X and Y chromosomes. Most often, Klinefelter syndrome
results from the presence of one extra copy of the X
chromosome in each cell (47,XXY). Extra copies of genes on
the X chromosome interfere with male sexual development,
often preventing the testes from functioning normally and
reducing the levels of testosterone.
Klinefelter syndrome and its variants are not inherited;
these chromosomal changes usually occur as random events during the formation of reproductive
cells (eggs and sperm) in a parent. An error in cell division called nondisjunction results in a
reproductive cell with an abnormal number of chromosomes.
Symptoms of this condition may include small, firm testicles, delayed or incomplete puberty,
breast growth (gynecomastia), reduced facial and body hair, infertility, tall height, abnormal body
proportions (long legs, short trunk, shoulder equal to hip size), learning disability and speech
delay.
According to statistics Klinefelter syndrome occur 1 in every 500 to 1,000 newborn males
has an extra X chromosome, making it one of the most common chromosomal disorders seen
among newborns. There are varieties of Klinefelter syndrome such as 48,XXXY and 49,XXXXY
are much rarer, occurring in 1 in 50,000 to 1 in 85,000 or fewer newborns.
References:
Chen H.. Klinefelter syndrome. Medscape Reference. July 2015;
http://emedicine.medscape.com/article/945649-overview
Frhmesser A, Kotzot D. Chromosomal variants in klinefelter syndrome. Sex Dev.
2011;5(3):109-23. doi: 10.1159/000327324. Epub 2011 Apr 29. Review
Klinefelter syndrome. Eunice Kennedy Shriver National Institute of Child Health and Human
Development. November 2013;
http://www.nichd.nih.gov/health/topics/klinefelter/Pages/default.aspx.
Klinefelter syndrome. Genetics Home Reference (GHR). January 2013;
http://ghr.nlm.nih.gov/condition/klinefelter-syndrome
 7. Williams syndrome
Williams syndrome is a developmental disorder that affects many parts
of the body. This condition is characterized by mild to moderate intellectual
disability or learning problems, unique personality characteristics,
distinctive facial features, and heart and blood vessel (cardiovascular)
problems. Young children with Williams syndrome have distinctive facial
features including a broad forehead, a short nose with a broad tip,
full cheeks, and a wide mouth with full lips. Many affected
people have dental problems such as teeth that are small,
widely spaced, crooked, or missing. In older children and
adults, the face appears longer and more gaunt.
This is caused by the deletion of genetic material from a specific region of chromosome 7.
The deleted region includes 26 to 28 genes, and researchers believe that a loss of several of these
genes probably contributes to the characteristic features of this disorder.
CLIP2, ELN, GTF2I, GTF2IRD1, and LIMK1 are among the genes that are typically deleted
in people with Williams syndrome. Researchers have found that loss of the ELN gene is
associated with the connective tissue abnormalities and cardiovascular disease (specifically
supravalvular aortic stenosis) found in many people with this disease. Studies suggest that
deletion of CLIP2, GTF2I, GTF2IRD1, LIMK1, and perhaps other genes may help explain the
characteristic difficulties with visual-spatial tasks, unique behavioral characteristics, and other
cognitive difficulties seen in people with Williams syndrome. Loss of the GTF2IRD1 gene may
also contribute to the distinctive facial features often associated with this condition.
Most cases of Williams syndrome are not inherited but occur as random events during the
formation of reproductive cells (eggs or sperm) in a parent of an affected individual. These cases
occur in people with no history of the disorder in their family. Williams syndrome affects an
estimated 1 in 7,500 to 10,000 people.
References:
Carrasco X, Castillo S, Aravena T, Rothhammer P, Aboitiz F. 2005. Williams syndrome:
pediatric, neurologic, and cognitive development. Pediatr Neurol. Mar;32(3):166-72.
Eckert MA, Galaburda AM, Mills DL, Bellugi U, Korenberg JR, Reiss AL. 2006. The
neurobiology of Williams syndrome: cascading influences of visual system impairment? Cell
Mol Life Sci. Aug;63(16):1867-75.
Pober BR. Williams-Beuren syndrome. N Engl J Med. 2010 Jan 21;362(3):239-52. doi:
10.1056/NEJMra0903074. Review. Erratum in: N Engl J Med. 2010 Jun 3;362(22):2142.
Schubert C. 2009. The genomic basis of the Williams-Beuren syndrome. Cell Mol Life Sci.
Apr;66(7):1178-97.
8. Charcot-Marie-Tooth Syndrome
 Charcot-Marie-Tooth disease is a group of progressive disorders that
affect the peripheral nerves. Peripheral nerves connect the brain and spinal
cord to muscles and to sensory cells that detect sensations such as touch,
pain, heat, and sound. Damage to the peripheral nerves can result in loss
of sensation and wasting (atrophy) of muscles in the feet, legs, and hands.
The disease usually becomes apparent in
adolescence or early adulthood, but onset may occur
anytime from early childhood through late
adulthood. Symptoms of Charcot-Marie- Tooth
disease vary in severity, even among members
of the same family. Some people never realize they have the disorder, but most have a moderate
amount of physical disability. A small percentage of people experience severe weakness or other
problems which, in rare cases, can be life-threatening. In most affected individuals, however,
Charcot-Marie-Tooth disease does not affect life expectancy.
CMT1A results from a duplication of the gene on chromosome 17 that carries instructions for
producing the peripheral myelin protenin-22. CMT2 can result from alterations in many genes,
including MFN2 and KIF1B (CMT2A); RAB7A (CMT2B); LMNA (CMT2B1); TRPV4
(CMT2C); BSCL2 and GARS (CMT2D); NEFL (CMT2E); HSPB1 (CMT2F); MPZ (CMT2I
and CMT2J); GDAP1 (CMT2K); and HSPB8 (CMT2L). Certain DNM2 gene mutations also
cause a form of CMT2.
The pattern of inheritance varies with the type of Charcot-Marie-Tooth disease. CMT1, most
cases of CMT2, and most intermediate forms are inherited in an autosomal dominant pattern.
This pattern of inheritance means that one copy of the altered gene in each cell is sufficient to
cause the disorder. In most cases, an affected person has one affected parent. CMT4, a few
CMT2 subtypes, and some intermediate forms are inherited in an autosomal recessive pattern,
which means both copies of the gene in each cell have mutations. Most often, the parents of an
individual with an autosomal recessive condition each carry one copy of the mutated gene, but
do not show signs and symptoms of the condition.
References:
Baets J, De Jonghe P, Timmerman V. Recent advances in Charcot-Marie-Tooth disease. Curr
Opin Neurol. 2014 Oct;27(5):532-40. doi: 10.1097/WCO.0000000000000131. Review
Bassam BA. Charcot-Marie-Tooth disease variants-classification, clinical, and genetic features
and rational diagnostic evaluation. J Clin Neuromuscul Dis. 2014 Mar;15(3):117-28.
El-Abassi R, England JD, Carter GT. Charcot-Marie-Tooth disease: an overview of genotypes,
phenotypes, and clinical management strategies. PM R. 2014 Apr;6(4):342-55. doi:
10.1016/j.pmrj.2013.08.611. Epub 2014 Jan 13. Review
9. SchmidFraccaro syndrome
 Cat eye syndrome is a rare chromosomal disorder that
may be evident at birth. Individuals with a normal
chromosomal make-up have two 22nd chromosomes,
both of which have a short arm, known as 22p, and a
long arm, called 22q. However, in individuals with cat
eye syndrome, the short arm and a small region of the
long arm of chromosome 22 (i.e., 22pter-22q11) are
present three or four times (trisomy or tetrasomy) rather
than twice in cells of the body.
Associated symptoms and findings may vary greatly in range and severity, including among
affected members of the same family. While some may have few or mild manifestations that may
remain unrecognized, others may have the full spectrum of malformations. However, in many
cases, characteristic features of the disorder include mild growth delays before birth; mild mental
deficiency; and malformations of the skull and facial (craniofacial) region, the heart, the kidneys,
and/or the anal region.
` Cat eye syndrome is named for coloboma of the eye, an often bilateral finding in some
affected individuals. The syndrome has been recognized for more than a century. The presence of
coloboma occurring along with anal atresia (see Symptoms above) was initially considered
primary features of the syndrome. However, cat eye syndrome was more specifically defined in
1965, when researchers reported that some affected individuals have only one or neither of these
features. The diagnosis is currently based on the presence of extra chromosomal material derived
from chromosome 22.
Diagnosis criteria typically requires at least two of the ocular coloboma, anal atresia, and
renal malformations; or one of the above accompanied by minor symptoms; or the combination
of any five or more minor symptoms. Cat Eye Syndrome is estimated to afflict 1 in 50,000 to 1
in 150,000.
Treatment is largely dependent on the phenotype of the patient and the severity of
symptoms. Ocular coloboma cannot be corrected; however, eyesight can be improved using
prescription eyewear in mild cases. In addition, heart and anal malformations and hernias can
usually be corrected using surgery. Skin tags can also be removed by simple procedures.
References:
Footz TK, et al. Analysis of the Cat Eye Syndrome Critical Region in Humans and the Region of
Conserved Synteny in Mice: A Search for Candidate Genes at or near the Human Chromosome
22 Pericentromere. Genome Res. 2001;11:1053-70.
Johnson A, et al. A 1.5-Mb contig within the cat eye syndrome critical region at human
chromosome 22q11.2. Genomics. 1999.
Chen, H. (2006). Cat eye syndrome. Atlas of genetic diagnosis and counseling (pp. 136-137,138). Totowa, New
Jersey: Humana Press

10. Wolf-Hirschhorn syndrome

 Wolf-Hirschhorn syndrome is a condition that affects many parts of the body. The
major features of this disorder include a characteristic facial appearance,
delayed growth and development, intellectual disability, and seizures.
Almost everyone with this disorder has distinctive facial features, including a
broad, flat nasal bridge and a high forehead. This combination
is described as a "Greek warrior helmet" appearance. The eyes
are widely spaced and may be protruding. Other characteristic facial features
include a shortened distance between the nose and upper lip (a short
philtrum), a downturned mouth, a small chin
(micrognathia), and poorly formed ears with
small holes (pits) or flaps of skin (tags).
Additionally, affected individuals may have asymmetrical facial features and an
unusually small head (microcephaly).
Wolf-Hirschhorn syndrome is caused by a deletion of genetic material near the end of the
short (p) arm of chromosome 4. This chromosomal change is sometimes written as 4p-. The size
of the deletion varies among affected individuals; studies suggest that larger deletions tend to
result in more severe intellectual disability and physical abnormalities than smaller deletions.
The prevalence of Wolf-Hirschhorn syndrome is estimated to be 1 in 50,000 births. However,
this may be an underestimate because it is likely that some affected individuals are never
diagnosed. For unknown reasons, Wolf-Hirschhorn syndrome occurs in about twice as many
females as males.
References:
Battaglia A, Carey JC. Wolf-Hirschhorn syndrome and Pitt-Rogers-Danks syndrome. Am J Med
Genet. 1998 Feb 17;75(5):541.
Nieminen P, Kotilainen J, Aalto Y, Knuutila S, Pirinen S, Thesleff I. MSX1 gene is deleted in
Wolf-Hirschhorn syndrome patients with oligodontia. J Dent Res. 2003 Dec;82(12):1013-7
South ST, Hannes F, Fisch GS, Vermeesch JR, Zollino M. Pathogenic significance of deletions
distal to the currently described Wolf-Hirschhorn syndrome critical regions on 4p16.3. Am J Med
Genet C Semin Med Genet. 2008 Nov 15;