Prenatal diagnosis of fetal syndromes

Abstract A syndrome is a pattern of multiple anomalies arising due to a single known causative factor. Ultrasonography has enabled us to recognize many fetal anomalies and dysmorphic features. Recognition of the anomaly pattern leads to the diagnosis of a particular syndrome. This enables us to counsel prospective parents and aids in management. We present a selection of fetal syndromes in the form of a pictorial essay.

A syndrome is a patt ern of multiple anomalies thought to be pathogenetically related and not known to represent a single sequence or a polytopic Þ eld defect. [1]The constituent anomalies of a syndrome result from a single known cause.The anomalies usually involve multiple systems and do not bear a cause-eff ect relationship between themselves (i.e., they are not a sequence).
The etiologic factor could be a chromosomal abnormality, a mutant gene defect, an infective agent, or a teratogenic drug or addictive substance.However there are still many situations where the etiology has not been resolved. [2]er the past years, the role of the fetal imaging specialist has evolved from just listing the anomalies detected in a fetus to recognizing the speciÞ c syndrome or sequence or association of which these anomalies are components of.This facilitates proper counseling of the parents as well as management planning.
The ability to provide as clear information as possible is of great importance during this period of turmoil and confusion in the prospective parents.Such information includes matt ers related to fetal prognosis, the need for invasive testing, obstetric management plan, short-and long-term neonatal prognosis, and neonatal management decisions.Contact with support groups will go a long way in aiding the parental understanding of the condition.A good resource in this direction is NORD (National Organization for Rare Disorders).Oft en, it is the imaging/fetal medicine specialist who coordinates the eff orts of the obstetrician, geneticist, clinical dysmorphologist, neonatologist, and other relevant specialists.
The suspicion of a set of anomalies/abnormalities being a syndrome may be due to one or more of the following: 1. Known pattern of anomalies: An example is cystic dysplastic kidneys with encephalocele, which arouses the suspicion of Meckel-Gruber syndrome.2. Recurrence of a set patt ern of anomalies: An example is recurrent left diaphragmatic hernia with facial cleft ing which would suggest the possibility of Fryns syndrome.Recurrence is a hallmark of single-gene defects, which may be autosomal or X linked, recessive or dominant.It becomes very important to get all the information regarding the previous aff ected pregnancy or pregnancies, including clinical and laboratory details and pictures, if available.An att empt should always be made to examine the aff ected index child.3. History of consanguinity.4. Family history: Construct a pedigree chart. 5. History of teratogenic exposure.
It should be emphasized that a syndrome typically consists of a number of features or anomalies, but a given case may only show a few of these anomalies.In other words, not all cases of the same syndrome would manifest with the same group or combination of anomalies.Again, we can site the example of Meckel-Gruber syndrome.The presence of any two of the following three anomalies, viz, encephalocele, cystic dysplastic kidneys, and postaxial polydactyly, against the background of a normal karyotype would justify the diagnosis of the syndrome.Also, there is the variant of the Meckel-Gruber syndrome which presents with Dandy-Walker malformation instead of an encephalocele.
It is the routine of a structured and detailed fetal USG examination (anomaly scan) that enables the recognition of a syndrome presenting without historical clues.The presence of a syndrome should be especially suspected if multisystem abnormalities are detected.All the anomalies/ dysmorphisms detected should be listed and a possible syndromic relationship should be explored.The recognition of a set of anomalies as a potential syndrome is aided by databases such as OMIM (Online Mendelian Inheritance in Man) and LDDB (London Dysmorphology Database).
Whenever there is history of a syndrome in a previous pregnancy or pregnancies, all the features of the syndrome should be noted and those that can be recognized by prenatal USG should be short-listed, and these features or anomalies should be speciÞ cally looked for and documented as being present or absent.Many syndromes need detailed scrutiny of the face, extremities, genitalia, etc. Three-dimensional (3D) USG oft en assists in the study of these anatomical regions.One example is 3D demonstration of midface hypoplasia in craniosynostosis syndromes.A given syndrome has its own natural history and may manifest earlier or later in fetal life or even postnatally   Thus we see that prenatal USG is capable of recognizing syndromic patt erns of anomalies.This is of great importance and has direct management implications.
. The diagnosis of a syndrome is complete only with a postabortal fetal study (which includes external examination, x-rays, and autopsy) or detailed neonatal examination.Invasive methods like fetal tissue sampling allow a speciÞ c diagnosis of chromosomal normality or abnormality.Single-gene syndromes that are suspected on prenatal USG may be conÞ rmed by biochemical, molecular, or cytomolecular techniques.A typical example would be demonstration of unbalanced translocation involving 17p13.3 by ß uorescent in situ hybridization in Miller-Dieker syndrome.Some syndromes do not have USG-detectable fetal features.Prenatal molecular diagnosis off ers the only means for diagnosis in such instances.Chorion villus sampling, amniocentesis, and fetal blood sampling are the techniques which yield fetal tissue or cells for testing.Fetal syndromes may be classiÞ ed on the basis of lethality (or absence of lethality), major system involved, etiology, and so on.It would not be possible here to provide a comprehensive listing and description of all the syndromes.The following are a few examples: 1. Beckwith-Weidemann syndrome (sporadic or AD): The main feature is the triad of macrosomia, omphalocele, and macroglossia.Other features include hepatomegaly, nephromegaly, placentomegaly, and polyhydramnios [Figure 1].Differential diagnoses to be considered include Down and Zellweger syndromes.2. Walker-Warburg syndrome: (AR) Constituent anomalies are hydrocephalus, agyria (lissencephaly type II), retinal detachment, encephalocele (HARD +/− E syndrome).Other features include cataract, micro-ophthalmia, buphthalmos, and congenital muscular dystrophy [Figure 2]. 3. Wolf-Hirschhorn syndrome: (chromosomal -4p deletion) Lead clue is severe early-onset IUGR with normal Doppler Þ ndings.Other features include 'Greek helmet' facial appearance with prominent glabella, rectangular nose, downturned mouth, hypospadias, cardiac and urinary tract defects [Figure 3]. 4. Turner syndrome: (Chromosomal -monosomy X -45X0) The main feature is cystic hygroma.Other features include hydrops, IUGR, coarctation of aorta, and horseshoe kidney.Fetal karyotyping clinches the diagnosis [Figure 4].Diff erential diagnosis includes Noonan syndrome.

Figure 10 :
Figure 10: Toxoplasmosis.Fetal hepatosplenomegaly is seen with ascites.Maternal serology was positive for toxoplasma