Medical Genetics - V. M. Zaporozhan 2005

Chromosomal Diseases
General Symptoms of Chromosomal Diseases

Chromosomal Disorders manifest as syndromes involving multiple Congenital Malformations. The diagnostic features of chromosomal syndromes can be divided into three groups:

1. General signs that raise suspicion of chromosomal anomalies (mental or physical underdevelopment, craniofacial dysmorphism, dermatoglyphic changes, internal organ defects).

2. Features most commonly associated with specific syndromes. For instance, Edwards' syndrome presents with dolichocephaly in 90% of cases and flexor positioning of the hand in 96%. Patau syndrome typically features cleft lip and palate, microphthalmia, Polycystic Kidney Disease, and polydactyly in roughly 70% of cases. Down syndrome exhibits an upward slant of the eyes in over 90% of cases and a transverse palmar crease (simian crease) in 60%.

3. Pathognomonic features specific to a particular syndrome. For example, cri-du-chat syndrome is characterized by a distinctive cry resembling a cat's mewing. As a rule, polyploidy and Changes in the number and Structure of autosomes present with specific symptoms during Pregnancy and are diagnosed in newborns. Chromosomal disorders associated with alterations in the number and Structure of Sex Chromosomes generally follow a milder clinical course.

GENERAL SYMPTOMS OF POLYPLOIDY AND Autosomal anomalies

During pregnancy

1. Threatened Miscarriage.

2. Intrauterine growth restriction (diagnosed via serial ultrasound scans).

3. Oligohydramnios or polyhydramnios.

4. Gestational toxicosis.

5. Premature birth, less frequently a full-term pregnancy.

General symptoms

1. Hypotrophy or hypoplasia at birth.

2. Psychomotor developmental delay in infants and toddlers.

3. Intellectual disability in older children (typically severe).

4. Growth retardation.

5. Infertility.

Facial and cranial dysmorphism

1. Microcephaly.

2. "Dysmorphic facies": ocular micro-anomalies (upward or downward slant of the eyes, hypo- or hypertelorism, epicanthus, etc.), low-set and malformed auricles; microgenia (mandibular hypoplasia), among others.

Upper and lower extremities

1. Single transverse palmar crease, single flexion crease on the 5th digit and other dermatoglyphic variations, clinodactyly of the 5th digit, Syndactyly, polydactyly.

2. Sandal gap deformity of the FOOT.

3. Rocker-bottom foot.

4. Transverse plantar crease.

Internal Organs

Congenital malformations of The Heart and major Blood Vessels, Brain, genitourinary and digestive tracts, as well as other Organ Systems, alongside endocrine and immune system dysfunctions, are frequently observed.

As an exception, the following symptom complexes occur:

1. Mental retardation without any developmental defect^s.

2. Developmental defects accompanied by normal mental development.

3. Isolated (single) developmental defects.

SYMPTOMS OF DISEASES CAUSED BY CHANGES IN THE NUMBER AND STRUCTURE OF SEX CHROMOSOMES

Chromosomal disorders resulting from changes in the number and structure of X-chromosomes generally tend to follow a milder clinical course. This milder presentation of these syndromes is attributed to the inactivation of extra X-chromosomes during embryonic development.

These Chromosomal diseases are typically characterized by the following features: — intellectual development is often below average, but brain malformations are not as pronounced as in autosomal anomalies. Many patients have normal intelligence, and some even above average;

— phenotypic abnormalities primarily affect The Development of the reproductive organs and stature; developmental malformations do occur, particularly in Turner syndrome, but they are less frequent and less severe;

— the definitive phenotype usually forms during adolescence, with Turner syndrome being the exception, as its distinct clinical signs are already evident in newborns;

— mild forms may occur, which are detected only through population-based screening studies.