Medical Genetics - V. M. Zaporozhan 2005

Methods for Diagnosing Hereditary Diseases
Syndromological Analysis

Syndromological analysis is the evaluation of a patient's phenotype (including minor anomalies, Congenital Malformations, and other clinical signs) to identify a consistent pattern of features for diagnostic establishment. Most hereditary syndromes are diagnosed based on a characteristic clinical picture. Genetic Disorders stem from Mutations that manifest as a complex of specific symptoms (syndromes). Notably, identical mutations in different patients result in similar phenotypes. Individuals with hereditary pathologies resemble each other more closely than they resemble their biological parents. Therefore, syndromological analysis is of paramount importance in diagnosing genetic conditions.

When analyzing a patient's phenotype, special attention is paid to minor anomalies and malformations. Minor anomalies can occasionally occur in healthy individuals (ranging from 0 to 6). However, patients with hereditary disorders typically exhibit a higher number of developmental minor anomalies and/or a specific combination of them. Syndromological Analysis of the patient's phenotype is fundamental for diagnosing the most well-known and prevalent Monogenic Diseases and syndromes characterized by malformations, such as Achondroplasia, Apert syndrome, Franceschetti syndrome, and many others. This method serves as an adjunctive tool in diagnosing Chromosomal Disorders, which are typically characterized by specific craniofacial dysmorphisms and malformations that help select a cohort of patients for cytogenetic testing. In some chromosomal syndromes, the patient's phenotype is so distinct that the syndrome can be diagnosed with high probability based solely on clinical examination data. Classic Examples include patients with Down syndrome, Turner syndrome, and Klinefelter syndrome. Nevertheless, the Diagnosis of a chromosomal disorder must always be confirmed by Cytogenetic Methods. This necessity arises from the existence of genocopies, meaning that Gene Mutations can produce a phenotype mimicking a chromosomal syndrome. For instance, a genocopy of Turner syndrome is Noonan syndrome (an autosomal dominant disorder). Cases have also been documented where Down syndrome was mistakenly diagnosed in hypothyroid patients based solely on facial features without considering other specific clinical markers.

Syndromological analysis is an important complementary method in diagnosing hereditary Connective Tissue disorders (such as Marfan Syndrome and Ehlers-Danlos syndrome), certain storage diseases (such as the characteristic "coarse facies" in patients with mucopolysaccharidosis), and other inherited Metabolic Disorders.

In some cases, examining not only the patient but also their relatives (identifying specific micro- and macrosymptoms of the disorder) can be crucial. If physical examination of relatives is not feasible, family photographs may be utilized. Analyzing the phenotype of a patient's relatives through family photographs can sometimes help identify likely carriers of the pathogenic gene, thereby clarifying the mode of inheritance.

Atlases of hereditary syndromes are widely used to refine the diagnosis of genetic disorders. In our region, the most popular reference atlas is "Hereditary Syndromes and Medical-Genetic Counseling" (S. I. Kozlova et al., 1996), which describes 460 syndromes, 148 of which are illustrated with photographs.

The end of the book features a diagnostic index designed to help locate a specific syndrome based on a set of symptoms observed in the patient. For example, Asymmetry of the trunk, face, and limbs is described in this book in relation to 9 syndromes, macrosomia in relation to two, and so forth. If necessary, the patient's phenotype can be compared with the photographs provided in the atlas. Since patients with hereditary disorders resemble each other more than they resemble their healthy relatives, this comparison proves highly useful for establishing an accurate diagnosis.

The following atlases have been published in English:

1. Jones K. L. Smith’s recognizable patterns of human malformation. — 5-th ed. — Philadelphia: WB Saunders, 1997.

Contains descriptions of the most common syndromes accompanied by photographs of patients.

2. Gorlin R. J., Cohen M. M., Levin L. S. Syndromes of the HEAD and Neck. — 3-rd ed. — New York: Oxford University Press, 1990.

Descriptions of malformations and minor Developmental anomalies of the head and neck in both common and rare hereditary syndromes.

3. Taybi H., Lachman R. Radiology of syndromes, metabolic disorders and skeletal dysplasias. — 4-th ed. — St. Louis: Mosby, 1996.

A comprehensive Overview of hereditary disorders characterized by skeletal involvement.