Pediatric Medical Genetics - S.I. Smiyan 2003

Chromosomal diseases
General remarks

Chromosomal Disorders encompass pathological conditions clinically manifested by multiple Congenital Malformations, the GENETIC BASIS OF which stems from deviations in the normal amount of chromosomal material within the body's Cells, that is, caused by genomic or chromosomal Mutations.

Most chromosomal disorders are sporadic in nature, meaning they arise As a result of genomic or chromosomal mutations in the Gametes of healthy parents or during the early Divisions of the zygote, rather than being inherited across generations. This is due to high mortality rates in infancy, as well as sexual underdevelopment and Infertility. The phenotypic basis of chromosomal disorders is rooted in disruptions during the early Embryonic period. Consequently, pathological changes take shape as early as the prenatal stage of development, either causing embryonic or fetal demise or establishing the primary Clinical presentation right from birth. An exception is represented by sexual development anomalies, which mainly manifest during Puberty.

The three most common chromosomal disorders were described as clinical developmental syndromes long before their association with Chromosomal aberrations was established.

These are Down syndrome, discovered in 1866; Klinefelter syndrome, described in 1942; and Turner syndrome, the first clinical description of which was made by N.A. Shereshevsky in 1925, and subsequently described by J. Turner in 1938. The discovery of chromosomal number aberrations in these patients in 1959 marked the beginning of The Study of novel Chromosomal Diseases. Throughout the 1960s, clinical cytogenetics fully emerged: numerous malformation syndromes caused by numerical or structural aberrations of specific Chromosomes were discovered, their overall frequency among newborns and in Spontaneous Abortion material was determined, and the incidence of syndromes associated with individual chromosomes was established.

Advances in identifying all Selection/39.html">Human chromosomes and their individual segments, achieved in human cytogenetics during the 1970s, shaped the modern scope of clinical cytogenetics, which continues to evolve today.

The current period is characterized by the delineation of cytogenetically and clinically distinct syndromes caused by imbalances in specific segments across virtually all 22 autosomes and the 2 sex chromosomes.

Chromosomal pathology plays a significant role in human Embryonic and Fetal mortality as well as in the overall incidence of multiple malformations in newborns. On average, about 40% of diagnosed spontaneous abortions are attributed to chromosomal abnormalities. Approximately 6% of all stillbirths exhibit alterations in the chromosomal apparatus. Out of every 1,000 live births, 3 to 5 infants have chromosomal disorders. Furthermore, if all cases of multiple congenital malformations are taken as 100%, chromosomal aberrations account for 35–40% of them.

All of this underscores the necessity for obstetricians, pediatricians, pediatric endocrinologists, psychoneurologists, orthopedists, pathologists, and other specialists to understand the Etiology, clinical presentation, diagnostic principles, Treatment, and Prevention of this major group of pathological conditions.

The Diagnosis of hereditary disorders must be based on genealogical analysis (a thorough study of family history across several generations), the twin method, cytological studies, biochemical genetics Methods, dermatoglyphics, endocrinological methods, and—most importantly—the identification of typical symptoms characteristic of Hereditary diseases.