Phenotypic abnormalities: Terminology and classification

Abstract

Clinical morphology has proved essential for the successful delineation of hundreds of syndromes and as a powerful instrument for detecting (candidate) genes (Gorlin et al. [2001]; Syndromes of the Head and Neck; Oxford: Oxford University Press. 1 p]. The major approach to reach this has been careful clinical evaluations of patients, focused on congenital anomalies. A similar careful physical examination performed in patients, who have been treated for childhood cancer, may allow detection of concurrent patterns of anomalies and provide clues for causative genes. In the past, several studies were performed describing the prevalence of anomalies in patients with cancer. However, in most studies, it was not possible to indicate the biologic relevance of the recorded anomalies, or to judge their relative importance. Are the detected anomalies common variants, and should they thus be regarded as normal, or are they minor anomalies or true abnormalities, indicating a possible developmental cause? Classification of items in the categories of common variants (disturbances of phenogenesis with a prevalence >4%), minor anomalies (disturbances of phenogenesis with a prevalence </=4%), and malformations (disturbances of embryogenesis) should allow weighing the importance of the scored items in the population under study, and should facilitate assessment of developmental disturbances (if any) in a study group. The lack of published consensus in the literature led us to produce a classification list with a twofold goal. First, we wanted to enhance uniformity in the scoring and classification of apparently abnormal physical findings by a nomenclature for errors of morphogenesis detectable on surface examination, and secondly a uniform classification system. This should allow investigators to evaluate systematically the presence of patterns in phenotypic anomalies, in the general population, and in patients with various disorders, suspected to be a developmental anomaly. Also, normal values may be obtained this way. Second, the list will allow a determination of the importance of the collected symptoms in a study population. We tested the feasibility of the application of the classification list in a study population: the list was piloted in a group of patients who have had cancer as a child, to detect patterns of anomalies related to specific types of tumors.

Observational Cohort Study of Pregnancy Outcome after First-Trimester Exposure to Fluoroquinolones

“…Congenital malformations were classified as major or minor by two experts according to established standards (21)(22)(23). Major birth defects were defined as structural abnormalities of medical, surgical, or cosmetic relevance.…”

Elements of morphology: General terms for congenital anomalies

“…The present authors, all members of the Elements of Morphology group, used as source for the general terms the series of publications that previously defined these [Smith, 1975;Spranger et al, 1982;Opitz et al, 1987;Merks et al, 2003]. We selected terms that were still in use (for example we did not consider the term "anomalad" as the term was discontinued in 1987 [Opitz et al, 1987]).…”

“…We use "substantial departure" here to imply that a particular anomaly is found in a small fraction (typically <2.5%) of the population or, in the case of measurable anomalies, the measured sign falls outside the normal reference range for the population (> or <2 SD from the mean). A more liberal threshold (<4%) has been advocated by others [Marden et al, 1964;Merks et al, 2003]. Anomalies, either major or minor (including malformations, deformations, disruptions, dysplasias, and sequences), can occur as isolated phenomena or as component manifestations of broader patterns or syndromes and are causally heterogeneous.…”

“…Disruption can affect several tissue types in a well-demarcated anatomical region and the phenotypic abnormalities may not conform to the boundaries normally imposed by embryonic development [Merks et al, 2003]. For example, interruption of the regional blood supply to a developing limb leads to ischemia, necrosis, and sloughing of the body part during development resulting in structural damage.…”

Supernumerary Nipple Children with Different Types of Malignancies

“…So we believe that; association of SN with cancer is not coincidence. The presences of SN were described as a malformation by Merks et al [7]. Also; in classical textbooks and comprehensive compilations the anomalies in association with SN are categorized based on organ systems [4].…”