What are congenital diseases?
Congenital means “born with something,” and congenital diseases refer to disorders in which there is an abnormality in the shape of the body or the function of organs at birth.
The opposite term, acquired, refers to a disease that develops due to causes that occur after birth.
It has been reported that the incidence rate of congenital diseases in Japan is about 2%.
It can affect any organ, including the brain, heart, or digestive tract, and the severity varies.
The reasons for the development of congenital diseases remain largely unknown, but for those that are known, it is believed that there are four main patterns.
Causes of congenital disorders
1. Chromosomal abnormalities
There are 23 pairs of chromosomes in the nucleus of human cells, totaling 46, and each chromosome contains multiple genes.
It is a congenital disease that occurs when an abnormality occurs in the number or structure of chromosomes during the developmental process of egg and sperm formation, or during the division of a fertilized egg, and is said to account for approximately 25% of congenital diseases. Examples include trisomy 21 (Down syndrome) , in which there are three copies of chromosome 21, and trisomy 13, in which there are three copies of chromosome 13. It
is a disease that involves genes, but chromosomal abnormalities are often caused by mutations and are not necessarily inherited from parents.
2. Single gene abnormalities
Congenital disorders caused by a single gene abnormality include disorders that are inherited from parents according to Mendelian laws.
If the gene for a disease is on an autosome, it is inherited as a dominant or recessive genetic disorder; if the gene for a disease is on a sex chromosome, it is inherited through sex-linked inheritance (X-linked inheritance).
Representative diseases include familial coli polyposis, a dominant genetic disease, phenylketonuria, a recessive genetic disease, and sex-linked hemophilia.
It is said to account for approximately 20% of congenital diseases.
3. Multifactorial inheritance
This is a disease caused by multiple genetic abnormalities and environmental factors after birth, and is thought to account for approximately half of all congenital diseases.
This pattern also includes Hirschsprung’s disease, congenital heart disease, and lifestyle-related diseases such as diabetes and high blood pressure.
4. Environment and teratogens
Birth defects can occur when a pregnant woman is exposed to teratogens, such as radiation, certain drugs, or environmental substances, or when she becomes infected with an infectious disease, such as rubella or toxoplasmosis.
It is said to account for approximately 5% of congenital diseases.
Major diseases of chromosome abnormalities
Trisomy 21 (Down Syndrome)
Trisomy 21 (Down syndrome) occurs when there are three copies of chromosome 21 instead of two (called trisomy 21).
In most cases of trisomy 21 (Down syndrome) , the chromosomes do not separate properly during the cell division process between the sperm and egg cells of the parents (chromosomal nondisjunction), resulting in a fertilized egg having three copies of chromosome 21.
For this reason, even if both parents are healthy, there is a certain probability that a baby will be born with trisomy 21 (Down syndrome) .
It is known that the possibility of developing trisomy 21 (Down syndrome) increases with maternal age, with reports indicating that the risk is less than 0.1% in women aged 20-25, but approximately 1% at age 40.
In addition to characteristic facial features such as slightly slanted eyes and a flat face, and physical symptoms such as muscle weakness, there may also be developmental delays.
There are also many cases where congenital heart disease such as endocardial defect and ventricular septal defect, and digestive abnormalities such as duodenal atresia and imperforate anus are also present.
Prenatal testing can be performed at around 10 to 15 weeks using the Quattro test, which can be performed using blood, or NIPT (NIPT is a non-invasive prenatal test) . NIPT (NIPT) has a detection rate of over 95% and a false positive rate of around 0.3%, making it highly reliable.
A definitive diagnosis is made by amniocentesis.
Major diseases caused by single gene abnormalities
Phenylketonuria
Phenylketonuria is a congenital metabolic disease in which the enzyme that converts phenylalanine, an essential amino acid that must be ingested from food, into another amino acid called tyrosine is weak, resulting in the accumulation of phenylalanine in the body and the reduction of tyrosine.
It is a recessive genetic disease caused by an abnormality in the phenylalanine hydroxylase (PAH) gene.
This means that if both parents are carriers of the PAH gene, there is a 1 in 4 chance that a child will be born with the disease.
It is a relatively rare disease, occurring in approximately 1 in 80,000 people, with approximately 500 patients in Japan.
Brain development disorders occur between a few months after birth and around two years of age, and symptoms include microcephaly, epilepsy, and mental retardation.
It also causes symptoms such as a characteristic urinary odor and albinism, such as red hair or pale skin.
The test is performed after birth through newborn mass screening, in which a blood sample is taken from the sole of the foot.
Special milk and a low-protein diet can be used to reduce dietary phenylalanine intake and control the levels of phenylalanine in the blood within a certain range, preventing the onset of symptoms.
Major diseases with multifactorial inheritance
Congenital heart disease
Congenital heart disease refers to a condition in which the structure of the heart or blood vessels is abnormal from birth.
The heart is made up of four chambers: the left atrium, left ventricle, right atrium, and right ventricle. Each chamber is separated by valves and walls to prevent blood from flowing backwards or mixing with other blood.
Congenital heart disease can include holes in the walls that separate rooms, narrowed valves, or abnormal attachment of blood vessels.
There are many types of congenital heart disease, and although their severity varies, the overall incidence rate is approximately 1%.
It is thought that the disease is caused by a combination of multiple genetic abnormalities and environmental factors during pregnancy (maternal smoking and drinking, taking certain medications, infections such as rubella).
The most common congenital heart disease is ventricular septal defect, a hole in the wall separating the left and right ventricles, which accounts for approximately 60% of all cases.
Other common conditions include pulmonary artery stenosis, a narrowing of the pulmonary artery, the blood vessel that carries blood from the heart to the lungs, and atrial septal defect, a hole in the wall separating the left and right atria.
Fetal ultrasound can determine whether or not a fetus has congenital heart disease as early as 20 weeks.
If it is discovered, detailed postnatal treatment plans can be discussed at a specialized hospital before birth.
After birth, your baby’s heart will be examined in detail using tests such as an electrocardiogram, X-rays, and cardiac ultrasound, as well as cardiac catheterization.
If the burden on the heart is small, observation may be sufficient, but if there are significant structural changes to the heart and it is under a great deal of strain, early treatment with medication or surgery is necessary.
Major diseases caused by environmental and teratogenic factors
Congenital Rubella syndrome
If a mother has rubella during early pregnancy, the rubella virus can be transmitted to the fetus and cause a condition called congenital rubella syndrome in the newborn.
The three major symptoms are congenital heart diseases such as ventricular septal defect and patent ductus arteriosus, hearing loss, and cataracts, but a variety of other symptoms can also be seen, including retinopathy, hepatosplenomegaly, thrombocytopenia, developmental disorders, and mental retardation.
If the condition does develop, treatment may include surgery for congenital heart disease or cataracts.
However, the most important thing is to prevent infection, and women who may become pregnant should get vaccinated.
【References】
- MSD Manual – Overview of Congenital Anomalies
- Hokkaido University Center for Environmental Health Sciences – Incidence of congenital anomalies
- National Cerebral and Cardiovascular Center – Children’s Heart Disease
- Rare Disease Information Center – Phenylketonuria
- National Institute of Infectious Diseases – Congenital rubella syndrome
Article Editorial Supervisor
Dr Hiroshi Oka
NIPT specialist clinic, MD
Graduated from Keio University, School of Medicine
