In studies of birth defects clinical dysmorphology constantly confronted with the phenomenon of pleiotropy. Congenital defects are pleiotropy, when the only primary pathogen causes abnormalities in more than one organ system in different parts of the embryo or in multiple structures that arise at different times of fetal life. Agent responsible for the formation of malformations may be mutant gene and teratogen.
Pleiotropic developmental defects appear in two different ways, depending on the mechanism of action of a pathogenic agent. If the agent causes many anomalies in parallel, a set of abnormalities called syndrome. If the mutant gene or teratogen affected at one point of time only one organ system, breaking it and thus causing other pleiotropic defects, as secondary defects, such defects are called sequence.
Pleiotropic syndromes can be explained on the example of an autosomal dominant syndrome, branchio-OTO-renal dysplasia. It has long been recognized that patients with abnormalities of the branchial arches, influencing the development of neck and auditory structures, are at high risk of renal anomalies. For example, the syndrome of branchio-OTO-renal dysplasia consists of abnormal development of the cochlea and the external ear, cysts and fistulas of the neck, dysplasia of the kidneys and malformation of urinary system.
The mechanism of this Association is explained by the fact that the formation as ear and kidney in mammals use a common conservative set of genes and proteins. This syndrome is caused by mutations in one of these genes, EYA1, which encodes protein phosphatase functioning in the development of hearing AIDS, and kidney. Similarly, the syndrome Rubinstein-Taybi is caused by loss of function of coactivator transcription, leading to abnormalities of transcription of many genes.
An example of a sequence is the formation of a high cleft palate and small lower jaw, called the Robin sequence. The sequence of Robin develops due to the fact that growth restriction of the mandible to 9 weeks of gestation causes the tongue to lie more posteriorly than normal, creating interference with the normal closure of the palatal plates, causing a split in the sky. The Robin sequence may be an isolated congenital defect of unknown etiology or the result of external influences on the forming of the lower jaw with a twin in the uterus a multiple pregnancy
This phenotype can also be an integral part of the disease, known as Stickler syndrome caused by mutations in a gene, which encodes a subunit of collagen type II, manifested by an abnormally small lower jaw and growth disorders, joints and eyes. Sequence, Robin syndrome Stickler — the sequence itself because the mutant gene does not cause collagen disorders closing sky; forked sky is secondary to the primary defect in the growth of the jaw.
Whatever the reason, cleft palate with Robin sequence differs from true primary split of the sky, with other causes with different prognosis and complications for the child and family. Knowledge of dysmorphology and genetic principles necessary for the development of a correct diagnosis of each type of defects and the understanding that different primary causes are associated with different predictions. These and other examples illustrate the principle that the clinical practice of dysmorphology based on the scientific Foundation of developmental biology. For this reason, the practitioner should have a practical knowledge of the basic principles of developmental biology and be familiar with how abnormal function of genes disrupts development of their patients.