Understanding the Causes of Congenital Malformations
Etiology of Malformations
Etiologic factors responsible for malformations differ according to whether they intervene before, during, or after fertilization. Before fertilization, these are genetic abnormalities, which are transmitted by the laws of inheritance.
Hereditary Factors
Simple Transmission of Inherited Malformations
A single gene is abnormal. The modes of transmission are differentiated by character: dominant, recessive, or sex-linked.
- Autosomal Dominant (e.g., achondroplastic dwarfism). If only one parent carries the gene tare, 50% of the children will be affected.
- Autosomal Recessive (e.g., certain forms of microcephaly). It is necessary that the abnormal gene is present in both parents. The risk to offspring is one to four.
- Sex-Linked Inheritance (e.g., certain forms of hydrocephalus). Transmission of recessive traits carried on the X chromosome. A woman, apparently healthy, transmits the disease gene to half of her sons, who are born sick, and half of her daughters who, although apparently healthy, are carriers.
Complex Hereditary Transmission of Malformations
- Cleft Lip and Palate Division: 0.6 to 1.6% of all births, more often male; risk of recurrence of 3% in first-degree relatives (first cousins and second cousins). Increased risk after the birth of two children affected by tare (9%).
- Pyloric Stenosis: 1 to 3% of all births, more often male (5 times more males affected).
- Equinus Varus Foot Deformity: 1% of all births, more often male; risk of recurrence of 2% among relatives of the first grade.
- Dysplasia of the Hip: 1% of births (with a geographical variation in frequency), more frequent in females (one male child for every 7-8 female children), risk of recurrence in first-degree relatives, according to sex.
- Congenital Heart Disease: Its causes are manifold, but it is likely that a given genotype predisposes to a specific abnormality of cardiac development. The proportion of affected first cousins is 3 to 4% for ASD, and 1 to 2% for patent ductus arteriosus.
- Anencephaly and Spina Bifida: The etiology of these malformations is not well understood. The frequency varies depending on various factors, particularly geography, climate, and very private newspapers (0.5% in France, 5.2 per 1000 in Ireland). Girls are affected three times more often than boys. The recurrence risk depends on the frequency in the general population.
- Mental Weakness: The study of IQ distribution suggests that it is of a multifactorial nature.
Chromosome Aberration
Chromosomal abnormalities are evident by studying the karyotype of the affected person and are due to accidents during meiosis or during one of the first cell divisions of the zygote. It may be a numerical aberration (trisomy, monosomy) or a structural aberration (deletion, multicentric inversion, ring chromosome, translocation).
- Autosomal Aberrations: Down syndrome or trisomy 21, Edwards syndrome (trisomy 18), Cri du Chat syndrome (deletion of the short arms of chromosome 4 or 5).
- Gonosomic Aberrations: Turner syndrome (XO), Klinefelter syndrome (XXY), Triple X syndrome (XXX), XYY syndrome.
Exogenous Factors
Role of the mother’s history, role of the date of insult, nature of exogenous factors.