Medical Genetics - V. M. Zaporozhan 2005

Classification, general characteristics, and symptomatology of hereditary diseases. General clinical diagnostics
Symptoms of hereditary and congenital pathology across various age periods

The following signs may indicate hereditary or congenital pathology.

In newborns

1. Prematurity is characteristic of many chromosomal syndromes.

2. Hypotrophy or hypoplasia at birth are present in numerous chromosomal and Monogenic Disorders.

3. Macrosomia is observed in Beckwith-Wiedemann syndrome, diabetic embryofetopathy, etc.

4. Microcephaly can be inherited as an autosomal recessive trait and serve as a symptom of many monogenic and chromosomal syndromes, sometimes resulting from Brain Damage caused by teratogenic factors (intrauterine infections, Hypoxia).

5. Macrocephaly may be a familial trait (a normal variant) or a manifestation of hereditary pathology (e.g., Achondroplasia, etc.).

6. Congenital Malformations (which may be hereditary or teratogenic in origin).

7. Minor developmental anomalies (more than 6) or their specific combination.

8. Underdevelopment or abnormal Development of the genitalia is a symptom of adrenal cortex dysfunction (adrenogenital syndrome) as well as many monogenic and chromosomal syndromes.

9. Muscular hypotonia and hyporeflexia are characteristic of neuromuscular disorders, Down syndrome, Prader-Willi syndrome, etc.

10. Seizures can be symptoms of inherited Metabolic Disorders and CNS malformations.

11. Acid-base imbalances (alkalosis, acidosis) are symptoms of inherited metabolic disorders.

In infants and toddlers

1. Failure to thrive (poor weight gain) is observed in enzymopathies, Chromosomal diseases, etc. Exposure of the fetus to teratogenic factors (e.g., alcohol) can cause both pre- and postnatal growth retardation.

2. Delayed psychomotor development. This is frequently a symptom of chromosomal diseases (especially when combined with specific minor Developmental Anomalies and congenital malformations). It is observed in many aminoacidurias (inherited Amino acid METABOLISM disorders). Sometimes it is a symptom of neuromuscular diseases.

3. Loss of previously acquired skills is a symptom of storage diseases (sphingolipidoses, leukodystrophies, etc.) and aminoacidurias.

4. Microcephaly.

5. Macrocephaly.

6. Deviations in physical development:

a) facial and cranial hypertrophy and Asymmetry (in hemifacial hypertrophy syndrome, etc.);

b) limb hypotrophy and asymmetry (Russell-Silver syndrome, etc.);

c) accelerated physical development (Beckwith-Wiedemann syndrome, etc.);

d) trunk and limb disproportion (long, slender limbs in Marfan Syndrome and homocystinuria; shortening of the proximal limb segments in achondroplasia, etc.);

e) shortened trunk (in spinal anomalies).

7. Diffuse or focal Skin pigmentation disorders. Café-au-lait spots are characteristic of neurofibromatosis, hypopigmented macules are observed in tuberous sclerosis, geographic map-like skin changes occur in incontinentia pigmenti, and multiple pigmented nevi are associated with basal Cell nevus syndrome. Generalized depigmentation is present in albinism, ectodermal Dysplasia, and phenylketonuria.

8. An unusual odor of sweat and urine is characteristic of inherited metabolic disorders (such as maple syrup urine disease, or phenylketonuria with its characteristic musty odor).

In preschool and early school-age children

1. Intellectual disability that becomes particularly noticeable during school age. It is typically preceded by delayed neuropsychological development in early childhood (Table 3.2).

2. At this age, certain inborn errors of metabolism (mucopolysaccharidosis) and neuromuscular disorders (muscular dystrophy) may first manifest, among others.

3. Chronic anemia may be caused by hemoglobinopathies (such as thalassemia) or red Blood cell metabolism disorders (for example, glucose-6-phosphate dehydrogenase deficiency).

4. Premature Puberty is observed in Beckwith-Wiedemann syndrome and the virilizing form of congenital adrenal hyperplasia in boys, among other conditions. It can also be a symptom of tumors affecting the Adrenal Glands, Ovaries, or the hypothalamic-pituitary system.

During adolescence and adulthood

1. Certain Nervous system disorders manifest during this period. Epilepsy and Friedreich's ataxia may develop in adolescents, whereas Wilson's disease, Huntington's chorea, and Alzheimer's disease typically appear in adulthood.

2. The early onset of midlife diseases (such as coronary artery disease or arterial Hypertension) is sometimes caused by monogenic disorders (e.g., familial hypercholesterolemia).

3. Hereditary nephritis and Polycystic Kidney Disease, where arterial hypertension may be one of the earliest clinical manifestations.

4. Underdevelopment of sexual characteristics. Primary Amenorrhea may occur in testicular feminization syndrome, while primary amenorrhea and underdeveloped secondary sex characteristics are typical of Turner syndrome (45,X). Underdeveloped secondary sex characteristics in boys are characteristic of Klinefelter syndrome (47,XXY).

Table 3.2. Main causes of intellectual disability

5. Infertility may be caused by chromosomal rearrangements, carriage of lethal genes, chromosomal disorders, or developmental malformations. For instance, uterine malformations can be a cause of Female Infertility. Male infertility associated with oligozoospermia is frequently observed in Klinefelter syndrome, cystic fibrosis, and Y-chromosome microdeletions.

6. Recurrent Pregnancy loss is observed in balanced chromosomal rearrangements, heterozygous carrier status for the same recessive lethal genes in both parents, and other hereditary pathologies.

7. Hereditary forms of malignant tumors may develop.