Medical Genetics - V. M. Zaporozhan 2005

Congenital Malformations
Congenital malformations: general concepts, population frequency, and specific weight in the structure of morbidity and mortality

The science of Congenital Malformations (CMs) is called teratology (from the Greek teratos meaning monster). Teratology studies the Etiology, Pathogenesis, clinical manifestations, diagnostic Methods, Treatment, and Prevention of congenital malformations.

According to G. I. Lazyuk et al. (1991), "a congenital malformation is a persistent morphological alteration of an organ or the entire Organism that exceeds the limits of normal structural variation, impairs organ function, and/or causes a cosmetic defect." These are defects that arise prenatally As a result of disrupted histogenesis and Organogenesis. As a rule, they are diagnosed at birth, but sometimes they become phenotypically apparent only after the child is born (as a result of impaired postnatal organ development). Examples of defects detected postnatally include patent ductus arteriosus and dental anomalies.

In medical literature, the terms congenital defect and developmental defect are also used as synonyms for congenital malformation. The term "monstrosity" as a synonym for developmental defects is no longer used due to deontological principles. METABOLISM/2.html">THE CONCEPT OF "congenital anomaly" is broader, encompassing not only malformations (morphological alterations of an organ) but also hereditary Metabolic Disorders.

Thus, a CM is a gross morphological (anatomical) developmental defect resulting in impaired function of an organ or the entire organism, or a major structural anomaly.

A distinction should be made between Congenital malformations and minor developmental anomalies. Minor developmental anomalies (MDAs), or stigmata of dysembriogenesis, are morphological alterations of an organ that exceed the limits of normal structural variation but do not impair its function and do not cause cosmetic de

fects. Alternatively, MDAs can be defined as morphological alterations of an organ that do not require cosmetic or any other medical correction. A healthy person normally may have from 0 to 6 minor developmental anomalies (attached earlobe, epicanthus, high-arched ("gothic") palate, clinodactyly of the fifth fingers, etc.). A high number or a specific combination of MDAs may indicate a hereditary condition, in which case the patient should undergo a thorough genetic evaluation.

While minor developmental anomalies can be Variants of the norm, congenital malformations represent pathology.

Differences in the incidence rates of congenital malformations have regional features and depend on the completeness of registration, clarity of Structure/97.html">Definitions (what exactly is classified as a CM), numerical, national, and age COMPOSITION OF THE studied population, historical, ethnic, and demographic factors, as well as geographical and environmental conditions. The average incidence of congenital malformations in newborns is 20-30 per 1,000 live births. Many defects are diagnosed at a later stage; therefore, the prevalence of children with malformations may reach up to 50 per 1,000 by the age of two, and up to 80 per 1,000 by the age of five.

In Ukraine, from 1993 to 2001, the average incidence of congenital malformations per 1,000 live births was 27.34 (Table 9.1). In 2001, the incidence of congenital malformations reached 30.5 per 1,000 live births. In the same year, congenital malformations accounted for 2.9% of the morbidity structure and 3.1% of the mortality structure in infants during their first year of life.

The incidence of many developmental defects is influenced by parental age and seasonal factors.

Malformation incidence and maternal age. Turner syndrome, Down syndrome, and musculoskeletal and respiratory malformations are more frequently observed in children born to young mothers (under 19 years of age) compared to mothers aged 22-35 years. This may be associated with the insufficient maturity of the hormonal control of ovulation and The phenomenon of "gamete overripeness." In mothers older than 35, there is an increased proportion of children with Down, Patau, and Edwards syndromes, as well as Central Nervous system defects (particularly cases of fetal anencephaly in primiparous women). The increasing incidence of chromosomal trisomies with maternal age is attributed to the extended duration from the initiation to the completion of oogenesis.

Table 9.1. Incidence of congenital malformations in Ukraine (1993-2001, per 1,000 live births)

Malformation incidence and paternal age. Paternal age correlates with an increased frequency of children born with cleft lip and palate, as well as monogenic dominant malformations (Achondroplasia, Apert syndrome, etc.), which is explained by the peculiarities of Spermatogenesis. Spermatogenesis takes approximately 70 days, during which germ Cell precursors pass through all Selection/3.html">Stages of development (proliferation, growth, maturation, and differentiation). Proliferation involves mitotic divisions of spermatogonia. The older the male, the greater the number of mitoses spermatogonia undergo and the more frequently DNA reduplication occurs. DNA reduplication is the process most commonly prone to errors leading to Gene Mutations. Thus, with advancing paternal age, the probability of gene mutations increases (affecting both dominant and recessive genes, though dominant mutations manifest immediately in the first generation).

Seasonal variations in the incidence of congenital malformations. Chromosomal nondisjunction During the first meiotic division in oogenesis is more frequently observed when conception occurs in February, March, April, May, and October. This leads to a higher rate of spontaneous abortions and Chromosomal Disorders in newborns. The minimum frequency of nondisjunction occurs when conception takes place in June, July, August, November, and December. These seasonal differences are attributed to delayed ovulation in women during the winter-spring and autumn periods and the phenomenon of "gamete overripeness."