Congenital Abnormalities

By
Muhammad-Amin Shamall Muhammad-Amin
Supervised by
Dr. Shang Abdulqadir
Summary
Congenital abnormalities are a common cause of perinatal and neonatal mortality, in
developing an undeveloped countries, they have multifactorial etiologist and 40% of
the cases are idiopathic, they are more common in populations that have
consanguineous marriages, many factors can cause congenital abnormalities in which
some can be explained and others have unknown causes. The developing of a child
which begins when the sperm fertilizes the egg goes through many complicated steps,
in which any of them may go wrong and cause an abnormality. Some congenital
abnormalities are inherited from the parents, and some may appear out of no where in
the new born child which can pass it on to his/her child.
Table of Contents
Summary..................................................................................................................................2
Congenital anomaly (CA).........................................................................................................3
Types of Anomaly................................................................................................................4
Associations in Anomalies....................................................................................................4
Teratogenesis............................................................................................................................4
Classification of Congenital Anomalies....................................................................................5
What causes congenital anomalies?..........................................................................................5
The role of genetics in the etiology of CM’s.............................................................................5
Monogenic inheritance.........................................................................................................6
Multifactorial and polygenetic inheritance............................................................................6
Chromosomal aberrations.....................................................................................................6
Environmental factors...............................................................................................................6
Physical teratogens...............................................................................................................6
Chemical teratogens..............................................................................................................6
Drugs and teratogenic effect.................................................................................................7
Proved drugs.....................................................................................................................7
Presumable drugs..............................................................................................................8
Possible drugs...................................................................................................................8
Biological teratogens............................................................................................................8
selected infectious agents..................................................................................................8
How to prevent congenital disorders and provide care for the affected children.......................9
Some Common congenital Abnormalities................................................................................9
Congenital malformation of the genital organs.....................................................................9
Congenital malformation of the nervous system: neural tube defect.....................................9
Cleft palate and cleft lip......................................................................................................10
Congenital malformation and deformation of the musculoskeletal system.........................11
References..............................................................................................................................11
Congenital anomaly (CA)
Is an anomaly that affects a body part or physiological function and it is present at
birth. It is caused by the abnormal ontogenetic development of the fetus. The process
is affected by genetic, environment, or both factors. The disturbance and the
abnormalities take place on the level of tissue, cell or molecule.

Types of Anomaly
 Malformation, is an abnormal development of an organ or tissue from the
beginning.
 Disruption, is a destructive process that affect an organ or tissue that started to
develop normally at first.
 Deformation, is an abnormal physical force that damages healthy organ or
tissue.
 Dysplasia, is caused by an abnormal organization of the cells in the organ or
tissue.

Associations in Anomalies
Some anomalies appear alone, or in sequence with other anomalies or even in
association, or in syndrome.

 Isolated anomaly, an anomaly that is not associated with any other conditions
(e.g. isolated polydactyly)
 Sequence, multiple anomalies that result from the pathogenic cascade caused
by primary insult (e.g. Potter’s sequence)
 Association, selected congenital anomalies tat tend to develop at the same time
(e.g. VATER association)
 Syndrome, a phenotypic trait anomaly (e.g. Down syndrome)

Teratogenesis
Teratogene, is an agent that can affect normal ontogenetic development and lead to
congenital abnormalities.

Mutagene, is an agent that can agent the genetic information on the level of DNA and
chromosomes, and cause mutation.

Some mutagens are also teratogens.

Classification of Congenital Anomalies
1. Congenital malformation of the nervous system
2. Congenital malformation of the eye, ear, face and neck
3. Congenital malformation of the circulatory system
4. Congenital malformation of the respiratory system
5. Cleft lip and cleft palate
6. Other congenital malformation of the digestive system
7. Congenital malformation of the genital organs
8. Congenital malformation of the urinary system
9. Congenital malformation and deformation of the musculoskeletal system
10. Other congenital malformation
11. Chromosomal abnormalities

This classification is made by WHO – International Classification of Diseases

(ICD)

What causes congenital anomalies?

 Genetic factors
 Environmental factors
 Unknown factors

Etiology of the congenital anomalies in man

10%
9%
6%
55%
20%

Etilogy unknown Multifactorial heredity Chromosomal aberration

Gene mutation Enviromental factors

The role of genetics in the etiology of CM’s

 Monogenic inheritance
 Polygenic / Multifactorial inheritance
 Chromosomal aberrations
 Others (epigenetics etc.)
Monogenic inheritance
Some congenital malformation are inherited as a monogenic trait. There are several
genes, whose mutation are associated with selected congenital anomalies. Example
includes, Marfan syndrome, Ehlers-Dahnols syndrome, Osteogenesis imperfecta,
Achondroplasia, Holoprosenecephaly, Xeroderma pigmentosum.

Multifactorial and polygenetic inheritance

 Polygenetic means that more than one gene is affected
 Multifactorial inheritance means that not only genetic factors but also
environmental factors affect the trait.

Chromosomal aberrations
Numerical aberrations include abnormalities in total number on chromosomes
Structural aberrations include abnormalities in the structure of the chromosomes.
Autosomal aberrations include abnormalities of the autosome. Gonosomal aberrations
include abnormalities of the gonosomes. Examples of chromosomal aberrations
includes: Down syndrome, Edward syndrome, Patau syndrome, Turner syndrome,
Triple X syndrome, XYY syndrome, and many others…

Environmental factors
There are many environmental factors that can cause congenital anomalies or are able
to cause them in specific situations. Those factors are known as teratogens. However
the effect of teratogens is dependent on the genetic.

There are three main groups of teratogens

1. Physical
2. Chemical
3. Biological

Physical teratogens
 X-rays (common diagnosis doses are not dangerous)
 Ionizing radiation (e.g. gamma radiation)
 High temperature (sauna, fever)
 Mechanical factors (amniotic bands, oligohydramnion)
Ultrasonography and electromagnetic field seem to be safe.

Chemical teratogens
 Chemical substances used in industry or agriculture (organic solvents, paints,
polychlorinated biphenyls, heavy metals)
 Alcohol (cause fetal alcohol syndrome)
 Products of cigarette smoking.
  Other drugs like cocaine and steroids
 Cytostatic and some other groups of medicaments.

Drugs and teratogenic effect

The current bloom of pharmaceutical industry provides many medicines each year,
and they all must be tested. Teratogenic effect can be species dependent it is possible
that the human embryo won’t be affected by the same substance that effect lets a cat
embryo. It can also be dose dependent, the same dose of a substance can be
teratogenic for human embryo but maybe not effective on a rat embryo. It might also
be time dependent lets say the substance can be teratogenic only in specific week of
pregnancy, it can only effect the development of specific organ.

During blastogenesis, the damage caused by the teratogens cause no anomalies. The
embryo is either able to repair all damage or stops development and die.
Organogenesis (3th-12th week of pregnancy) is the critical period for most teratogens.
The morphological anomalies are usually caused during this period. The second and
third trimester is not so critical, however the toxic effect of some substances is
pathologic as well.

The teratogenic effect of the drugs can be classified into

 Proved ones
 Presumable ones
 Possible ones
 And couldn’t excluded ones

Proved drugs
 Alcohol (facial dysmorphy, brain growth retardation, congenital anomalies
of the heart)
 Warfarin, is a medication used as an anticoagulant (chondrodysplasia
punctate, risk of abortion)
 Retinoids, is a class of chemical compounds that are vitamers of vitamin A
or are chemically related to it. Used to regulated epithelial cell growth
(anomalies like Di-George syndrome, anomalies of CNS, anomalies of the
internal ear)
 Aminopterine, amino derivative of folic acid, is and antineoplastic drug
with immunosuppressor properties often used in chemotherapy. And
Methotrexate, is a chemotherapy agent and immune system suppressant,
used to treat cancer, autoimmune diseases, ectopic pregnancy and for
medical abortions. (anomalies of cranium and skeleton, anencephaly)
 Thalidomide, medication used to treat a number of cancers including
multiple myeloma, graft-versus-host disease and a number of skin
conditions (abnormal development of long bones, phocomelia,
polydactyly, syndactyly, oligodactyly and other malformations)
Presumable drugs
 Phenytoine, is an anti-seizure medication (congenital anomalies of the heart,
failure of the CNS closure, cleft palate)
 Trimethadione, it is most commonly used to treat epileptic conditions that are
resistant to other treatments (anomalies of the heart, anomalies of the
urogenital system, mental retardation)
 Valproate, used to treat epilepsy and bipolar disorder, and to prevent migraine
headaches (facial dysmorphy, defects of CNS)
 Lithium, used for treating bipolar disorder (anomalies of the heart, Ebstain’s
anomaly)

Possible drugs
 Amphetamine, it is CNS stimulant used to treat attention deficit
hyperreactivity disorder, narcolepsy, and obesity (congenital anomalies of the
heart, exencephaly, atresia of bile ducts)
 Diazepam, a medicine that produces a calming effect (cleft lip and cleft palate)
 ACE-Inhibitors, a type of medicine used for the treatment of high blood
pressure and heart failure (hypoplysia of the skull, renal dysgenesis)
 Corticosteroids, a class of drug used to lower inflamations in the body and
reduce immune system activity (cleft palate, renal atrophy)
 Androgens, drugs that stimulate development of male sexual characteristics
(masculinization of the external genitelia)
 Progesteron, used with estrogens for hormone therapy for treating menopausal
symptoms and low sex hormones in women (virilization, anomalies of the
heart, anomalies of the CNS, defects of the extremities, esophageal atresia)

Biological teratogens
1. infectious agents
2. diseases of the mother, example: Diabetes mellitus, Phenylketonuria

selected infectious agents

 Rubivirus (cataract, deafness, heart anomalies, microcephaly, mental
retardation)
 Cytomegalovirus (microcephaly,chorioretinitis,deafness, hepatosplenomegaly)
 Varicella-zoster virus (microcephaly, chorioretinitis, defects of the extremities,
mental retardation, cataract)
 Parvovirus B-19 (hydrops fetalis, heart malformations)
 Influenavirus (failure of the CNS closure)
 Coxsackie virus (fetal pancreatitis and fetal meningoencephalitis)
 HIV (immunodeficiency, dysmorphy)
 Treponema pallidum (teeth development failure, IUGR, hydrops fetalis)
 Toxoplasma gondii (hydrocephaly, microcephaly, chorioretinitis, blindness)
How to prevent congenital disorders and provide care for the
affected children
To increases the chances for every couple to have a healthy child, to decrease the
consequences of potentially avoidable congenital abnormalities for those affected,
their families, the health care system, and the society they live in, and to support the
wellbeing of children with congenital anomalies, many measures should be taken to
address this issue.

1. Supporting family planning, letting the woman and the couple choose when to
have a child and deciding on their family size.
2. Ensuring a healthy balanced diet for women.
3. Reducing and removing teratogenic substances from the diet especially
alcohol.
4. Controlling infections in women of reproductive ages, and modify and
optimize maternal health by detecting and managing chronic illnesses linked
with increased risk of congenital abnormalities, such as type 2 diabetes and
epilepsy.
5. teaching physicians, nurses, allied health care practitioners in the recognition,
causes, and care of children with congenital anomalies.
6. Medical and social services align to provide timely treatments for children
with congenital disorders.
7. Showing and providing emotional and practical help for parents to let them
understand and control their risk of congenital ailments, and support families
with children with congenital problems.
8. Educating the public about congenital abnormalities.

Some Common congenital Abnormalities

Congenital malformation of the genital organs
Hypospadias, displacement of the urethral meatus ventrally and proximally from the
tip of the penis. Classified into three categories:

1. First degree, the urethral meatus is located on either the gland or the corona.
2. Second degree, the urethral meatus is located balanopenile furrow or coronal
sulcus.
3. Third degree, the urethral meatus is located in the junction of the penis and the
scrotum.

Congenital malformation of the nervous system: neural tube defect

Neural tube defect affects the brain and the spinal cord and it is the most common
among congenital anomalies
  Anecephaly, a total or partial absence of the brain, together with total
or partial absence of the cranial vault and the covering skin.
 Chraniorachichisis, the presence of ancephaly with a contiguous spine
defct without meninges covering the neural tissue.
 Iniencephaly, a rare and complex neural tube defect characterized by
extreme retroflexion of the head.
 Frontal encephalocele, herniation of brain tissue covered by meninges
through a defect in the frontal bone.
 Nasofrontal encephalocele, herniation of brain tissue, usually covered
by meninges, through an opening between the frontal bone and the
nasal and ethmoid bones.
 Cervical spine bifida, most cases develop hydrocephalus.
 Thoracic spina bifida, most cases will develop hydrocephalus.
 Lumber spine bifida, some cases will develop hydrocephalus.
 Sacral spine bifida, few cases will develop hydrocephalus.

Cleft palate and cleft lip

 Cleft palate, fissure of the palate, which can affect the soft and hard palate.
  Cleft lip, bilateral, partial or complete bilateral fissure of the upper lip that
may be associated with a cleft of the gum.
 Cleft lip, specific as unilateral, partial or complete unilateral fissure of the
upper lip that may be associated with a cleft of the gum
 Cleft hard palate with bilateral cleft lip, or complete bilateral fissure of the
upper lip, associated with a fissure of the palate.
 Cleft hard palate with cleft lip, specific unilateral, partial or complete
unilateral fissure of the upper lip, associated with a fissure of the palate.

Congenital malformation and deformation of the musculoskeletal system

 Talipes equinovarus, combination of forefoot and hindfoot in equinus and in
varus, meaning, the foot points downward and inward and is rotated outward
axially.
 Reduction defects of upper and lower limbs.
 Complete absence of upper limbs.
 Absence of upper are and forearm with the hand present.
 Absence of both forearm and hand.
 Absence of hand and fingers, absence of finger.
 Absence of the thumb.
 Longitudinal reduction defect of the radius
 Longitudinal reduction defect of ulna.
 Split hand, complete or partial absence of central fingers and metacarpals.
 Complete absence of the lower limbs.
 Absence of thigh and lower leg with foot present.
 Absence of both lower leg and foot.
 Absence of foot and toes.
 Absence of toes.
 Absence of the first toe.
 Longitudinal reduction defect of femur.
 Longitudinal reduction defect of tibia.
 Longitudinal reduction defect of fibula.
 Split foot, complete or partial absence of central toes and metatarsals.
References
 Congenital anomalies Etiology, diagnosis and incidence. Antonin sipek.
 The Prevalence and Types of Congenital Anomalies in Newborns in Erbil.
Galawezh O. Othman.
 Prevention of Congenital Disorders and Care of Affected Children: A
Consensus Statement. Gary L. Darmstadt, Christopher P. Howson, Gijs
Walraven, Robert W. Armstrong, Hannah K. Blencowe, Arnold L.
Christianson, Alastair Kent, Helen Malherbe, Jeffery C. Murray, Carmencita
D. Padilla, Salimah R. Walani.
 Birth Defects Surveillance: Atlas of Selected Congenital Anomalies.