Congenital malformations - Edocr

10 PART I GENERAL CONSIDERATIONS
between minor malformation and a normal
variant is often arbitrary and is primarily
based on the frequency of a finding
in general population. A normal variant
usually occurs in 4% or more of the population
as compared to minor malformations
which are present in less than 4% of
the normal population. It is common for
isolated minor anomalies to be familial.
Minor malformations are most frequent in
areas of complex and variable features
such as the face and distal extremities.
Minor malformations are relatively frequent
and a higher incidence may be noted
among premature infants and infants with
intrauterine growth retardation. In general,
minor malformations are more subtle, have
low validity of diagnoses, and are not reported
consistently. They are nevertheless
significant as they may be an indication
of the presence of a major malformation
and may also provide critical clues to the
diagnosis. The risk of having a major malformation
increases with the number of
associated minor malformations. It is estimated
that infants with three or more
minor defects have a 20–90% risk of
a major malformation; those with two minor
defects have 7–11% risk; those with
one minor defect have a 3–4% risk compared
to infants with no minor malformations
who have a 1–2% risk of a major
malformation. 2,3 Some of this variability
in risk is probably related to variability in
definition, documentation, and validity of
minor malformation diagnoses in different
studies.
E. Etiological classification of birth defects.
In order to achieve consistency among various
studies, a new hierarchical system of
classification was proposed recently. 24 This
new classification system divides all congenital
malformations into the following eight categories
based on etiology: (1) Chromosome
(C): for microscopically visible, unbalanced
chromosome abnormalities such as Trisomies;
(2) Microdeletion (MD): for all submicroscopic
chromosome abnormalities including
microdeletions, uniparental disomy, and imprinting
mutations such as 22q11 deletion
(DiGeorge syndrome) and 15q11 deletion
(Prader-Willi or Angelman syndrome);
(3) Teratogen (T): for known teratogens and
prenatal infections such as fetal alcohol syndrome
and congenital cytomegalovirus
(CMV) infection; (4) New dominant (ND):
for new dominant mutations such as achondroplasia,
Apert syndrome; (5) Familial (F):
for familial disorders not included as a new
dominant such as tuberous sclerosis, fragile
X syndrome; (6) Syndrome (S): for recognized
nonfamilial, nonchromosomal syndromes
such as Kabuki syndrome; (7) Isolated
(I): for isolated anomalies not included in
one of the above categories such as gastroschisis,
isolated cleft lip; and (8) Multiple
(M): for unrelated anomalies from more than
one system with no unifying diagnosis such
as VACTERL and MURCS. This classification
system would allow cases to be classified to
one category only, the highest in the list of
categories applicable.
In summary, congenital anomalies are an
important cause of morbidity and mortality both
in the perinatal period and later in life, and despite
a considerable decline in the prevalence
of some types of congenital malformations,
around 2–3% of all births are still associated
with a major congenital malformation. A better
understanding of the etiology and pathogenesis
of these defects has led to several prevention
strategies over the years. Rubella immunization
and avoidance of teratogenic drugs in women of
reproductive age, use of folic acid supplementation
and maintenance of euglycemia in
diabetic patients during the periconception
period, premarital and preconception genetic
counseling to couples at risk of certain genetic
disorders, and screening for Down syndrome
in presence of advanced maternal age are a few