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Microcephaly: general considerations and aids to nosology
1Department of Medical Genetics, Shodair Children's Hospital, Helena, Montana 59604.
Insights
Microcephaly, a smaller head circumference, can be primary (at birth) or secondary (acquired). Syndromal microcephaly presents complex diagnostic challenges requiring advanced resources.
Area of Science:
- Medical Genetics
- Developmental Biology
- Pediatrics
Background:
- Microcephaly is defined by occipito-frontal head circumference (OFC) below established norms, adjusted for age, sex, and parental OFC.
- Distinguishes between "relative" microcephaly (small head, small child) with better prognosis and "absolute" microcephaly.
- Classifies microcephaly as "primary" (abnormal at birth) or "secondary" (acquired postnatally due to various insults).
Purpose of the Study:
- To explore the complex nosology of syndromal and non-syndromal microcephaly.
- To illustrate the challenges in classifying microcephaly due to overlapping manifestations and pleiotropy.
- To highlight the utility of specialized databases in understanding microcephaly.
Main Methods:
- Utilized standard definitions for microcephaly, including occipito-frontal circumference (OFC) measurements and adjustments.
- Reviewed literature and case examples of syndromal microcephaly associated with normal or abnormal intelligence.
- Employed specialized resources such as McKusick's Catalog of Mendelian Inheritance in Man (MIM) and electronic databases (OMIM, POSSUM, SYNDROME, MEDLINE).
Main Results:
- Some syndromal microcephaly cases, including "primordial dwarfs" and certain genetic syndromes, can present with normal intelligence.
- The diagnostic classification of microcephaly is complicated by pleiotropy and overlapping clinical features.
- Electronic databases significantly aid in navigating the complexity of microcephaly nosology.
Conclusions:
- The classification of microcephaly is intricate, demanding sophisticated diagnostic approaches.
- Understanding the genetic and developmental basis of microcephaly is crucial for accurate diagnosis and prognosis.
- Advanced information retrieval tools are essential for comprehensive study of microcephaly.
Abstract:
Microcephaly is defined as an occipito-frontal head circumference (OFC) 2 or more standard deviations below the mean for age and sex using the new Roche et al. [Pediatrics 1987;79:706-712] charts, and corrected for parental OFC by the method of Weaver and Christian [J Pediatr 1980;96:990-994]. "Relative" microcephaly, i.e., a small head on a small child, may be associated with a much better intellectual prognosis than absolute microcephaly, although the average IQ of children with absolute microcephaly ascertained in a normal school system is normal when compared with that of appropriate control children. "Primary" microcephaly means an abnormal OFC at birth (corrected for gestational age and length), and "secondary" microcephaly a normal birth OFC with later, acquired microcephaly due to deceleration of brain growth reflecting infection, trauma, intoxication, metabolic disease, the Rett syndrome, or a true CNS degenerative disease. Some cases of syndromal microcephaly may be associated with normal intelligence including some "primordial dwarfs," children with Dubowitz syndrome, FAS, mild SC-Roberts syndrome, and an occasional Brachmann-de Lange individual. The nosology of (syndromal) microcephaly is extraordinarily complex and requires the assistance of special library resources and information retrieval expertise. At a minimum, it requires McKusick's Catalog of Mendelian Inheritance in Man (MIM); however, we find that our work is greatly enhanced by recently developed electronic databases such as MIM-online (OMIM), POSSUM, SYNDROME, and MEDLINE, as well. Three groups of syndromal and non-syndromal microcephaly are discussed selectively in order to illustrate the marvels of pleiotropy in human development and its abnormalities and the difficulties encountered in splitting and lumping entities with overlapping manifestations.