Hilde Van Esch, Centre for Human Genetics, University Hospital Leuven, Leuven, Belgium Jean-Pierre Fryns, Centre for Human Genetics, University Hospital Leuven, Leuven, Belgium
Dysmorphology is the study of human congenital malformations and combines concepts and knowledge of different medical fields, including embryology, paediatrics and clinical genetics.Introductory article
. How is Dysmorphism Defined? . Clinical Diagnostic Approach of a Dysmorphic Child . Molecular and Cytogenetic Basis of Dysmorphic Syndromes . Future Perspectives
How is Dysmorphism Defined?
The ﬁeld of dysmorphology has expanded dramatically over the last 25 years. New insights have been gained in the pathogenesis of variousstructural defects, leading to better diagnosis and the possibility for prenatal detection. Given the vast number, a listing of all known recognizable patterns of malformation goes beyond the scope of this review. Rather, this article provides an approach to the child that presents with a congenital malformation. Congenital defects can be divided into single defects in development and multiplemalformation defects or syndromes. Single primary defects in development can be further subdivided, according to the underlying morphogenic error that has resulted in the observed defect, into malformations, deformations and disruptions. A ‘malformation’ is a primary structural defect arising from a localized error during morphogenesis (Figure 1b). In most cases, the defect involves only a single structureas for example a cleft lip or neural tube defect. Genetic as well as environmental factors play an important role in the pathogenesis of malformations. This will be discussed further in this article. A ‘deformation’ is an alteration in shape or structure of a part that has differentiated normally (Figure 1c). Most deformations involve the musculoskeletal system and are caused by intrauterinepressure. This may be due to intrinsic factors because of neuromuscular problems within the fetus. This occurs, for example, in disorders involving muscle degeneration (e.g. myotonic dystrophy of Steinert (MIM 160900)) and disorders involving motor neurons, such as Werdnig–Hoﬀman type 2 disease (MIM 253550). Fetal crowding of extrinsic origin is usually due to a decreased volume of amniotic ﬂuid. Ineither case, the ability of the fetus to move and to kick is severely impaired resulting in decreased fetal movements and abnormal development of the musculoskeletal system. The most frequent observed congenital deformities are talipes equinovarus and hip dislocation. These might be isolated ﬁndings in an otherwise perfectly healthy child; however an underlying neuromuscular disorder always has tobe excluded. Especially, multiple joint contractures should alert the physician to the possibility of such a disorder. A ‘disruption’ occurs when there is the destruction of a previously normally formed part (Figure 1a). Two basic mechanisms are known that can produce a disruption. One involves the entanglement followed by the tearing apart or amputation of a normally developed structure, involvingmostly the limbs and digits, by amniotic bands. These amniotic bands are strands of amnion, ﬂoating within the amniotic ﬂuid. The second mechanism involves the interruption of the blood supply to a developing part, leading to infarction, necrosis and ultimately resorption of structures distal to the insult. Genetic factors only play a minor role in the pathogenesis of disruptions and theprognosis is determined by the extent and localization of the structure that is lost. When a single, primary defect during morphogenesis results in multiple abnormalities through a cascade of different effects and errors, this is called a ‘sequence’. For example the Potter sequence, consisting of low-birth weight, wrinkled skin, typical facial dysmorphism (Potters
Figure 1 Clinical examples...
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