Approach to the Child with Birth Defects

Lecture #16

November 12 (Monday), 2001

Required Reading: Principles of Medical Genetics

Gelerhter TD, Collins FS, Ginsburg D

1998 Williams and Wilkins

Pages: review -171-194, new -280-290

Understand information in this handout!

  • Be able to distinguish major anomalies (such as cleft palate, congenital cardiac defects) from minor anomalies (single transverse palmar crease)

It is important to specifically look for, characterize, and precisely describe and document any major or minor anomalies that may be present in an individual when considering a genetic condition.

Major anomalies are often defined as anomalies or malformations that create significant medical problems for the patient or that require specific surgical or medical management. Major anomalies or malformations generally are not considered a variation of the normal spectrum.

Minor anomalies are often described as features that vary from those that are most commonly seen in the normal population but that, in and of themselves, do not cause increased morbidity.

    • Understand that many "normal" individuals may have a couple of minor anomalies, even perhaps a major anomaly, without having any particular syndrome or disorder. If several minor anomalies and/or a few major anomalies are present in one individual, a clinician must suspect an underlying syndrome or association and evaluate that individual accordingly.

    • Recognize that both major and minor anomalies may be associated with particular syndromes or, in many cases, may be an isolated finding in an otherwise healthy individual. For example, a cleft lip or palate may be an isolated finding (non-syndromic) in an otherwise healthy individual, or, may be part of a syndrome in an individual with multiple birth defects.

    • Understand that what appears to be the same birth defect or congenital anomaly may have completely different etiologies in different individuals. For example a cleft lip and/or palate may be associated with a chromosome disorder, exposure to a known teratogen, amniotic bands, an autosomal dominant single gene disorder, or a combination of various genetic and environmental factors (multifactorial). It is also important to consider and remember the timing of fetal development when considering the cause of a birth defect (you will learn more about this in your embryology course).

    • Characterization of all major and minor anomalies in great detail as precisely as possible is essential to help arrive at the correct diagnosis. Most often, it is not just one major anomaly or one minor anomaly that makes a diagnosis but rather it is a constellation of major and minor anomalies that point to a specific syndrome diagnosis or known association.

    • Understand the importance and utility of genetic counseling and genetic evaluations in the diagnostic work-up of individuals with congenital anomalies. Understand the roles of a genetic counselor in the case of stillborn infants including the importance of non-directive counseling and special issues related to infant or fetal death.

Genetic counseling at the time of fetal or of an infant’s death involves the same principles that genetic counseling does at other times. However, because of the death, it is often a very difficult time for the family to discuss and "hear" about further diagnostic evaluations and/or recurrence risks. It is usually not a good time for parents to make future reproductive choices at the time of the death of a child. Thus, it is best to have families return to clinic a few weeks or months after the loss for further counseling. It is also important that, at the time of death of the infant or birth of the stillborn infant, that the genetic counselor/geneticist works closely with other members of the health care team, including social workers, to make sure parents have a chance to see their baby, understand what happened, address issues surrounding their loss, and discuss issues relating to a burial or memorial service.

  • Understand the concepts of:


Sequence or Field Defect






A syndrome is generally recognized and defined as a well-characterized constellation of major and minor anomalies that occur together in a predictable fashion presumably due to a single underlying etiology which may be monogenic, chromosomal, mitochondrial, or teratogenic in origin. For instance Down Syndrome trisomy 21, (a numeric chromosome disorder - 47 XX or XY, +21) is a syndrome associated with a predictable constellation of major and minor anomalies that create a recognizable phenotype that allowing people who have seen other individuals with trisomy 21 to immediately suspect the diagnosis when they see another individual with the same condition, even though all of the characteristic anomalies (or features) are generally not present in any one affected individual.

An association is a group of anomalies that occur more frequently together than would be expected by chance alone but that do not have a predictable pattern of recognition and/or a suspected unified underlying etiology.

A sequence is a group of related anomalies that generally stem from a single initial major anomaly that alters the development of other surrounding or related tissues or structures. Potter’s sequence is recognized by a constellation of physical findings where the outward appearance of the newborn is often characterized by flattened abnormal facial features and deformations of the hands and feet. These features along with poor lung development are secondary to decreased amounts of amniotic fluid (oligohydramnios) which is most often due to major renal (kidney) abnormalities (eg a single major anomaly) associated with decreased fetal urine output.

The term field defect is often used to describe related malformations in a particular region and sometimes is used interchangeably with sequence. The Pierre-Robin sequence is in fact sometimes referred to as a field defect where a small jaw resulting in posterior displacement of the tongue causes a cleft palate. Thus, these birth defects are related to one another in a temporal and physical sense - being limited to that field or area of the head. Spina bifida with changes to the lower extremities and disruption of bowel and bladder dysfunction would be another example of a sequence or field defect.

A field defect, however can be associated with other anomalies in a syndrome such as velocardiofacial syndrome where affected individuals have often a characteristic facial appearance associated with their cleft palate and cardiac defects. This illustrates the importance of a comprehensive examination in reaching the correct diagnosis for an individual.

    • When considering dysmorphic features it is also important to keep in mind the various ways in which structures and tissues may become abnormal.

For instance a structure may be visibly abnormal due to a deformation. A deformation is caused by an abnormal external force on the fetus during in utero development that resulted in abnormal growth or formation of the fetal structure. For example, in fetuses that grow in a uterine environment where not enough amniotic fluid is present (oligohydramnios) as described above when discussing Potter sequence, the fetus may have a flattened face due to compression of the face against the uterine wall with no room for significant movement and full development of the face or facial features.

Another type of abnormality is known as a disruption where a fetal structure is growing normally and then growth is arrested due to something which disrupts the process. This is seen in the condition of amniotic bands where a digit or extremity may be growing normally but then growth is disrupted or discontinued due to the development of amniotic band at the end of that extremity. This may result in missing fingers, toes, or hands and feet. Oftentimes disruptions and deformations are relatively isolated and not associated with multiple congenital anomalies.

A malformation signifies that fetal growth and development did not proceed normally due to underlying genetic, epigenetic, or environmental factors that altered the development a particular structure.

Another type of generalized anomaly is related to an underlying tissue dysplasia where the intrinsic cellular architecture of a tissue is not normally maintained throughout growth and development. Many of the skeletal syndromes of short stature are due to dysplasia in the developing bone and cartilage.