Medical Genetics - V. M. Zaporozhan 2005

Classification, general characteristics, and symptomatology of hereditary diseases. General clinical diagnostics.
General principles of clinical diagnosis of hereditary diseases
Congenital malformations and microanomalies of development as signs of dysmorphogenesis

The Clinical examination of a patient with suspected hereditary pathology aims to identify signs of dysmorphogenesis. These are a component of many Hereditary diseases and manifest across virtually all body systems. Congenital Malformations and minor developmental anomalies indicate disruptions in morphogenesis and embryonic differentiation.

Congenital malformations (CMs) are permanent structural alterations in an organ or the entire body that exceed the normal range of structural variation, impair organ function, and/or cause cosmetic defects. They develop prenatally or (much less commonly) postnatally due to impaired further organ development (e.g., dental anomalies). In medical literature, synonyms for the term "congenital malformations" include "congenital anomalies" and "developmental defects."

The following terms are used to describe developmental defects.

Agenesis — complete Congenital absence of an organ.

Aplasia — congenital absence of an organ with the persistence of its vascular stalk.

Atresia — complete absence of a tubular channel or natural orifice.

Congenital hypotrophy — reduced body weight in a newborn or fetus. For older children, the terms "nanism" (dwarfism) or "microsomia" are used to denote reduced body size.

Heterotopia — presence of Cells, Tissues, or entire regions of an organ within another organ or in unusual anatomical locations where they normally should not be found.

Hypertrophy (hyperplasia) — an increase in the relative mass or size of an organ due to an increase in Cell number (hyperplasia) or cell size (hypertrophy).

Hypoplasia — underdevelopment of an organ manifested by a deficit in mass or dimensions (more than two standard deviations below the mean for a given age). The term "congenital hypoplasia" is sometimes applied to total body mass as a synonym for "congenital hypotrophy."

Dyschrony — alteration in the rate (acceleration or deceleration) of development.

Inversion — reverse (mirror-image) positioning of an organ.

Microsomia (gigantism) — increase in body dimensions.

Disorder of lobulation — increase or decrease in the number of lobes in the lung or Liver.

Oligo- — a reduction in the number of Organs or organ parts (oligodactyly — absence of one or more digits; oligogyria — absence of individual cerebral gyri).

Pagus — conjoined monozygotic twins ("siamese twins"): thoracopagus — joined in the chest region, craniopagus — in the HEAD region, ischiopagus — in the sacral region.

Pachy- — enlargement of an organ or its part (pachygyria — thickening of cerebral gyri; pachynychia — thickening of the Nails).

Persistence — retention of embryonic structures that normally disappear by a certain stage of development (patent ductus arteriosus). One form of persistence is non-closure (dysraphism) of an embryonic cleft (Spina bifida, cleft lip, cleft palate).

Poly- — presence of additional organs (polydactyly, polysplenia).

Syn- prefix denoting failure of Separation (Syndactyly — failure of digit separation).

Stenosis — narrowing of a tubular channel or natural orifice.

Duplication of an organ (duplication of the Uterus, aortic arch, etc.).

Ectopia — displacement of an organ, i.e., its Location in an unusual site (LOCATION OF THE Heart outside the thoracic cavity).

Minor developmental anomalies (MDAs), or stigmata of dysembriogenesis, are structural variations of an organ that do not impair its function and do not constitute a cosmetic defect, thus requiring no medical intervention.

MDAs can be divided into three groups:

1. Anthropometric (measurable) traits are defined by absolute or relative numerical values (body weight, height, head circumference, cephalic index, etc.). These data are compared with the normal distribution of the respective measurements within a population.

2. Alternative traits are either present or absent (Papillomas, fistulas, etc.). Some of these occur exclusively in specific hereditary syndromes (for example, vertical earlobe creases in Beckwith-Wiedemann syndrome).

3. Descriptive traits represent variations of normal characteristics that are difficult to quantify using standard Research Methods (changes in Skin keratinization, Hair Structure, etc.).

The number of minor anomalies of development (MADs) in healthy children ranges from 0 to 6. The most common include epicanthus, high palate, attached earlobes, flat nasal bridge, deformed auricles, clinodactyly of the fifth fingers, and others.

In hereditary diseases, the number of minor anomalies increases or specific combinations of them are observed. Since MADs serve as indicators of impaired morphogenesis and embryonic differentiation caused by both genetic and environmental factors, they aid in the accurate Diagnosis of hereditary pathologies when evaluated alongside other symptoms. When determining whether a detected minor anomaly indicates a genetic disorder, the ethnicity and phenotype of the child's parents must be taken into account.

The accuracy of diagnosing a hereditary disease and providing MEDICAL Genetic Counseling largely depends on how thoroughly developmental minor anomalies are identified during patient examination. For instance, isolated cleft lip and palate is inherited in a multifactorial manner, and the recurrence risk for the birth of an affected child is approximately 4%.

The combination of a cleft with hypertelorism points to frontonasal Dysplasia (an anomalad with a very low recurrence genetic risk), whereas its combination with hypotelorism is characteristic of holoprosencephaly (an autosomal recessive disorder with a 25% recurrence risk for subsequent affected children).

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Fig. 3.1. Hemihypertrophy:

a, b — facial hemihypertrophy; c — leg hemihypertrophy