TITLE:
Lethal Developmental Defects: An Overview
AUTHORS:
Ashutosh Halder
KEYWORDS:
Lethal Developmental Defect, Lethal Malformation, Neural Tube Defect, Chromosomal Abnormality, Amniotic Band Syndrome, Skeletal Dysplasia, Nonimmune Hydrops Fetalis
JOURNAL NAME:
Open Journal of Obstetrics and Gynecology,
Vol.4 No.16,
December
5,
2014
ABSTRACT: About 3% of all
conceptions are associated with major congenital malformations, many of them
are lethal developmental defect and genetic in origin or teratogenic (adverse
effects of the environment during gametogenesis or early embryogenesis).
Genetics with or without adverse environment has role in virtually every
developmental defect/malformation disorders in causation, predisposition,
susceptibility & modulation of disease. Advances in genetics, introduction
of triple marker screening, routine obstetric ultrasound examination into
obstetric practice & accesses to prenatal diagnosis helped in secondary
prevention (early detection & termination) of lethal developmental defects.
Ultrasound detection of fetal developmental defects/malformation is common now
and often decision on pregnancy solely based on ultrasonic morphological
description. This practice leads to difficulty in providing accurate counseling
as well as preventing disorder in subsequent pregnancy, in particular early.
Hence an understanding of reproductive genetics of major developmental
disorders is important for today’s perinatal care specialists. This overview
will outline the various lethal developmental defects observed in an advanced
reproductive genetics set up and various approaches adopted to derive
diagnosis. Detailed assessment of fetus after termination
of pregnancy (spontaneous/induced) for fetal anomalies was carried out in most
cases. As most cases was referred
after termination in formalin routine chromosomal analysis was not possible
however, in selected cases targeted FISH analysis with specific chromosomal
probe was carried out to confirm clinical diagnosis. Detailed evaluation of
fetus is important as this practice often helped in modification of genetic
counseling, as well as course of management in the next pregnancy. No molecular
diagnostic or screening work was carried out due to non availability of
information and facility in past. However, this is important today as many of
the lethal developmental defects are yet to be categorized etiopathologically,
and hence immediate need is to start clinical registry along with biorepository
of developmental defects cases for future research work on informative
families, in particular with multiple affected fetuses/sibs, using genomics,
proteomics, metabolomics, platforms.