Sunday, 16 August 2020

Trisomy 18 : What are the common association with Trisomy 18 which may be a common or an uncommon association but not impossible

 Trisomy 18 : What are the   common association with  Trisomy 18   which may be a common or  an  uncommon association but not impossible:  CPSs can be a significant  finding because there have  been reports in the literature over the years describing the association  of CPSc  with fetal aneuploidy specifically with trisomy  18 .CPCs appear to be present  in approximately one third of trisomy 18 fetuses.

Because of this association there is much debates to whether fetuses having CPCs  on ultrasound should undergo karyotyping It is clearly recommended that when  fetuses with CPCs  have  other sonographic finding invasive testing should be  offered. However  when  prenatal   sonography   by experienced personnel reveals that   the CPCs are isolated management  should be conservative. However  some investigators believe that fetuses having isolated CPCs  and no other  anomalies may still carry a risk  of aneuploidy  high enough  to justify amniocentesis. However  the critical component lies in whether an isolated CPC is in fact truly  isolated. This can  only be presumed once a detailed  fetal survey by experienced examiners has failed to reveal other structural abnormalities /markers .Therefore it is  imperative   that all fetuses with CPCs  undergo  a detailed fetal sonographic  anatomic survey    by someone who is skilled and expe4rienced in prenatal diagnosis.

Part II:  Whhat are the abnormalities associated with Trisomy  18

 

Association with Trisomy 18:- In trisomy 18 growth  is usually restricted .  CNS abnormalities   associated with Edward syndrome are A) choroid  plexus  cyst B)  abnormal  cisterna magna C) absent   corpus callosum  D) cerebella hypoplasia E)  ventriculomegaly G) strawberry shaped calvarium  and  F) neural tube defects.

Quite often, there are   few  skeletal abnormalities .    Skeletal abnormalities include   limb reduction defects, overlapping index finger, clubbed feet,, rocker bottom feet  and polydactyl.

Facial defects  are also sometimes seen  like  cleft lip and palate ,  micrognathia,  low set ears and microphthalmos.

Cardiovascular abnormalities in Trisomy 21 :    May be associated with  this syndrome are  omphalocele , diaphragmatic hernia,  hydronephrosis  and horseshoe kidney    . Umbilical cord cysts and double vessels umbilical cord may also be observed.

 

 

Several meta analyses have   been  reported in the literature with regard to fetuses with isolated CPCs . One  report  revealed  that  had a 0.27  %  incidence   of trisomy 18  and five had Down syndrome. Their study suggested  a likelihood ratio of 13 .8  for trisomy 18  and  1.87  for  Down syndrome contains  a summary of reported studies examining the incidence of  aneuploidy  in fetuses with isolated   CPCs  The   majority had no cases of aneuploidy   whereas eight  studies found an association of isolated CPCs with chromosomal  anomalies.

Snijders et al found CPCs in 505 of their  fetuses with trisomy 18 and in 1%  of chromosomally normal fetuses. However   because the vast majority   of affected  fetuses showed other    sonographic anomalies the risk   of isolated CPCs  was only  marginally increased   with a likelihood ratio less than 2 however the presence  of  just one other abnormality  increased in the risk 20 times. Recently we examined the prenatal sonographic features  of 38  fetuses with  trisomy 18 and found that 50%  had CPC  identified   but they were always  associated  with multiple   other sonographic  abnormalities  Recently  De vore also found the prevalence of CPCs  in trisomy 18  fetuses to be  53%  and when  these cysts were isolated they  were  not associated  with trisomy 18. In anther study by our group we found that  of 98  fetuses with isolated CPCs  no one  had aneuploidy   whereas of the 13 fetuses with CPCs   non had aneuploidy   whereas   of he 13 fetuses with CPCs  and major anatomic abnormalities  100%   had trisomy 18. Subsequently   one group of investigators found that all 131   fetuses with  isolated CPC  had normal karyotypes and all fetuses with aneuploidy had additional abnormalies.  In  addition we have shown that from a cost benefit point   of view   invasive testing based on the  presence of  isolated  CPCs  is not  justified.

Previously it has also been believed that large cysts or bilateral cysts increased the risk for aneuploidy some  evidence suggests that these larger cysts further increase the risk for trisomy 18   . However  this should still be regarded within the   context of whether other abnormalities’ are also present or  not . Although CPCs always resolve larger cysts may take longer  to undergo this process lending support to the observation that delayed resolution of CPCs may carry an increased risk for trisomy 18 .

One  must also   remember    that it has  been shown  that small unilateral lesions may be seen in chromosomally abnormal fetuses. Whether CPCs are unilateral or bilateral is probably  not significant  although  it is probably  the case  that larger   cysts also  tend to be   bilateral . In our study  of he 19 trisomy 18  fetuses  with  CPCs 79%    had bilateral  cysts of  these six  had a moth eaten appearance of the choroid plexus. On the other hand four fetuses had unilateral CPCs  of whom three had only a single cyst.

Unlike  for trisomy 18 a possible relationship between CPC and trisomy 21  is somewhat  controversial Some  studies have suggested  that CPCs  are associated  with Down syndrome in the second trimester . However  Bromely  showed that the incidence of CPCs in the normal population was the same as the incidence   of cysts among fetuses with Down syndrome . Thus they concluded that the presence   of CPCs  did not increase  a  patient’s  risk for  fetal  Down  syndrome In  a meta  analysis he authors reported  that isolated  CPCs  were associated  with a fetal  Down syndrome   risk of  1/880  which is the same as that of the general population.

Therefore in order  to increase  or decrease  one’s  suspicion of aneuploidy when  CPCs  are visualized  sonographically we believe  a through   detailed  examination  needs to be performed   of the remaining  fetal anatomy to rule out other  abnormalities  . 

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