1 1st Department of Obstetrics & Gynecology of the Postgraduate Center of Medical Education, Warsaw, Poland 2 Genetic Department of Institute of Psychiatry and Neurology, Warsaw, Poland

Archives of Perinatal Medicine 18(3), 173-177, 2012 CASE REPORT

Severe micrognathia in the first trimesterin complete trisomy 9

– a case report and literature review

JULIA BIJOK1, DIANA MASSALSKA1, ANNA MICHAŁOWSKA1, TOMASZ ROSZKOWSKI1, ALICJA ILNICKA2, BARBARA PAWŁOWSKA2, GRZEGORZ JAKIEL1

Abstract

Trisomy 9 is a rare chromosomal abnormality with a very poor prognosis depending mostly on the amount andexact location of the duplicated genetic material. Most of the fetuses with complete trisomy 9 are spontaneouslyaborted in the early first trimester and therefore it is uncommonly seen at the time of 11-14 weeks’ scan. Thediagnosis is usually made after fetal karyotyping performed for routine indications. We present a case of completetrisomy 9 diagnosed after chorionic villus sampling performed because of the detection of severe micrognathiaat 13 weeks gestation.

Key words: trisomy 9, micrognathia, prenatal diagnosis, first trimester, sonography

Introduction

Trisomy 9 is a rare chromosomal abnormality thatwas first described in 1973 by Feingold and Atkins [1].The clinical spectrum varies depending on the amountand exact location of the genetic material that is dupli-cated. The symptoms include intrauterine growth res-triction, facial dysmorphism (microcephaly, low setmalformed ears, bulbous nose, micrognathia, cleft pala-te) and abnormalities involving all organs – congenitalheart defects (ventricular septal defect, atrial septaldefect, patent ductus arteriosus, double outlet rightventricle), central nervous system malformations (Dan-dy-Walker malformation, ventriculomegaly, spina bifida,myelomeningocoele), skeletal deformities (club hand,rocker bottom feet, camptodactyly), genitourinary de-fects (genital hypoplasia, horseshoe kidney), diaphrag-matic hernia and other abnormalities [2-8].

A complete (non-mosaic) trisomy 9 has a prevalenceof 1:1000 recognized conceptions but it is a lethal con-dition and the majority of pregnancies progress intospontaneous abortion in the first trimester. Rarely dothe fetuses survive to the time when characteristic sono-graphic findings can be seen [4, 5, 9-11]. Recent advan-ces in prenatal testing have led to detection of more ca-ses in the first trimester of pregnancy. However, most ofthem are found incidentally by fetal karyotyping per-formed for routine indications such as maternal age or

abnormal serum screen [12, 13]. There are 40 cases ofprenatal diagnosis of complete trisomy 9 reported up todate in English literature but only 8 of them have beendetected in the first trimester [12-15]. Due to differentclinical manifestations of the syndrome, a characteristicmorphology is still not complete. We present a case oftrisomy 9 that was detected in the first trimester ofpregnancy by chorionic villus sampling conducted becau-se of an abnormal first trimester scan with a post mor-tem examination and a literature review.

Case report

A 39 year old gravida 2 was referred to our center atthe 13th week of gestation for Ist trimester scan, whichwas performed according to Fetal Medicine Foundation(FMF) standards by an experienced FMF-certified doc-tor. Her medical history was unremarkable. The scanrevealed a fetus of 66 mm with nuchal translucency of1.3 mm. The fHR was 153’ and the ductus venosus flowwas normal. An individual risk for trisomy 21 was 1:421;trisomy 18 – 1:641 and trisomy 13 – 1:11215. The anato-my scan revealed severe micrognathia (Fig. 1) and anabnormal four chamber view. A transabdominal chorio-nic villus sampling was performed and karyotypingshowed trisomy 9 (47,XY,+9 in 18 metaphases) withoutevidence of mosaicism. A fetal ultrasound at 17 weeks’gestation identified a severe micrognathia (Fig. 2),

J. Bijok, D. Massalska, A. Michałowska, T. Roszkowski, A. Ilnicka, B. Pawłowska, G. Jakiel174

absence of one orbit, cardiac anomaly (double outletright ventricle – DORV) and hand and foot anomalies(fixed fingers and toes – Fig. 3, 4).

Fig. 1. Severe micrognathia on the first trimester scan

Fig. 2. Severe micrognathia on the second trimester scan

Fig. 3. Abnormal hand with fixed fingerson the second trimester scan

The pregnancy was terminated at 19 weeks of gestationand a stillborn male fetus of 100 g (below 5th percentile)was delivered. A postmortem examination revealed mul-

tiple anomalies: a large fontanelle, severe facial dysmor-phism (low set malformed ears, small palpebral fissures,prominent nose with a bulbous tip, severe micrognathia– Fig. 5);

Fig. 4. Abnormal foot with fixed toes on the second trimester scan

Fig. 5. Post mortem examination of the fetus:severe micrognathia, low set ears, abnormal hand

short and webbed neck, absence of intergluteal fold,short penis, skeletal malformations, ulnar deviation ofthe wrist and laterally deviated overlapping fingers witha gap between the thumb, indix and the three remainingfingers. An autopsy and a cytogenetic confirmation fromfetal tissue was declined by the patient.

DiscussionA complete trisomy 9 regarding its diverse clinical

manifestation is considered to be lethal. The longest re-ported survival of a neonate with a complete trisomy 9was 3.5 months but the majority of neonates die withinhours after birth [16]. An early prenatal diagnosis andaccurate genetic counseling is crucial to the manage-ment of ongoing and subsequent pregnancies and helpsavoiding unnecessary maternal and fetal interventions.

Table 1. Cases of complete trisomy 9 detected in the first trimester

CaseAuthor,

year

Maternalage

(years)

Gestationalage

(weeks)

Indicationfor

karyotyping

Sonographicfindings in the first

trimester scan

Sonographic findingsin repeated scan (GA)

ProcedureKaryotype

(cells counted)Outcome

Postmortem

examination

1.Martinez,

1997– 12

Abnormalscan

NT – 4 mm – CVS Trisomy 9 TOP

2.Pinette,

199825 11

Abnormalscan

Hydrops,cystic hygroma

– AC Trisomy 9IUFD

17 Hbd

3.Murta,2000

30 12Abnormal

scan

NT – 9.1 mm, rDVF,rUVF VSD,

bilateral pyelectasias,hyperechoic bowel,

echoic intracardiac focus

– CVS Trisomy 9IUFD

14 Hbd+

4.

Sepulveda,2003

42 11Previous

trisomy 13none

(14) nuchal edema(16) IUGR, ventriculomegaly, pleural

effusions, mild ascites, bilateralhydronephrosis

CVSAC

47,XX,+9(40)47,XX,+9(118)

TOP17 Hbd

5. 38 12Abnormal

scanNT – 4.5 mm

(16) ventriculomegaly, absent cerebellarvermis, nuchal edema, hypoplastic left

heart, bilateral polydactyly, rocker-bottom feet, short femora

CVS 47,XY,+9(30)TOP

17 Hbd

6. 41 12 MA none – CVS 47,XY,+9(32)IUFD

17 Hbd

7. 40 12Abnormal

scanNT – 3 mm, rDVF

(24) IUGR, brachycephaly,diaphragmatic hernia, mediastinal shift,

bilateral hydronephrosisCVS 47,XX,+9(22)

IUFD31 Hbd

8.Schwen-demann,

2009– 11

Increased riskfor T18 on

serum screen

none(NT – 1.8 mm;

48th percentile growth)– AC 47,XY,+9 TOP

9.Present

case38 13

Abnormalscan

Micrognathia(17) retromicrognathia, absent orbit,

DORV, hand and foot anomaliesCVS 47,XY,+9(18)

TOP18 Hbd

+

MA – maternal age; GA – gestational age in weeks; NT – nuchal translucency; rDVF – reversed ductus venosus flow; rUVF – reversed umbilical vein flow; IUGR – intrauterine growth restriction;DORV – double outlet right ventricle; CVS – chorionic villus sampling; AC – amniocentesis; TOP – termination of pregnancy; IUFD – intrauterine fetal demise

J. Bijok, D. Massalska, A. Michałowska, T. Roszkowski, A. Ilnicka, B. Pawłowska, G. Jakiel176

We have performed a literature review on completetrisomy 9. We have searched Pubmed database since1973 using terms “trisomy 9” combined with “comple-te”, “non-mosaic”, “prenatal”, “ultrasound” and “sono-graphic”.

40 cases of complete trisomy 9 diagnosed prenatallyhave been found. Mean maternal age was 33 years, meangestational age at the ultrasound scan was 20 weeks.The most common abnormalities found sonographicalywere genitourinary (62.5%; mostly genital hypoplasia)and central nervous system malformations (60%; mostlyposterior fossa abnormalities).

Micrognathia was the most common facial mani-festation described in 7 cases (17.5%; 43.75% of all facialanomalies). In 5 cases there were no sonographic fea-tures present and the karyotyping was performed forroutine indications.

Among 40 cases diagnosed prenatally, there were 8detected in the first trimester but only one of themshowed structural anomalies in the ultrasound scan. Themost common indication for karyotyping was increasednuchal translucency (NT), which was present in fivecases. Abnormal Doppler flow was seen in two cases. Inthree cases there were no anomalies found in the firsttrimester scan. Four of the pregnancies were termi-nated, other four progressed into intrauterine fetal de-mise (see Table 1).

In 1993 Bromley and Benacerraf analysed theassociation of fetal micrognathia with chromosomalanomalies and fetal outcome. Interestingly, 25% of thecases showed chromosomal aberrations (trisomy 9 inone case) and only four of 20 reported fetuses survived[17]. This poor prognosis was confirmed by Luedders etal. last year [18]. These reports indicate a necessity offetal karyotyping when micrognathia is encounteredprenatally. To our knowledge it is the first report of amicrognathia seen in the first trimester scan leading toa diagnosis of a complete trisomy 9. Until this report theearliest case of micrognathia seen in trisomy 9 was at 16weeks’ ultrasound scan performed because of abnormalMSAFP level. As the morphology and sonographicfindings of trisomy 9 are similar to trisomy 18 and 13due to IUGR, micrognathia and elevated MSAFP it canbe easily mistaken with those more common aberrationsand should be taken into consideration, when observingthese anomalies [19-23].

Some authors reported increased nuchal translu-cency and abnormal ductus venosus flow in fetuses withtrisomy 9 [12, 14, 15]. Interestingly, both NT and ductusvenosus flow were normal in our case. The individual

risk for chromosomal aberrations (based on maternalage, nuchal translucency, fetal heart rate) was not in-creased and but for the detection of micrognathia andabnormal four chamber view in the first trimester, theCVS procedure would probably not have been per-formed.

The most common cardiac manifestation of the syn-drome is ventricular septal defect. We report a doubleoutlet right ventricle (DORV) which up to date has onlybeen seen twice in trisomy 9 prenatally [20, 24]. Most ofother structural anomalies described in previous reportswere seen at the post mortem examination in our case(facial dismorphy, genital hypoplasia, skeletal abnorma-lities). There was no posterior fossa manifestation,which is the most common central nervous system ano-maly seen in trisomy 9, but this alteration can not bediagnosed in the first and early second trimester.

The diagnosis of complete trisomy 9 after chorionicvillus sampling should be confirmed by other tissuesampling (amniotic fluid, fetal blood, placenta, skin) tominimize the risk of mosaicism or placental pseudo-mosaicism [12, 25, 26]. In this case there were 18 cellscounted from a standard culture and there was no signof mosaicism. Further testing and an autopsy were de-clined by the patient. There remains a risk of a mosai-cism but the clinical manifestation was consistent withcomplete trisomy 9.

To conclude, we present a first case of completetrisomy 9 diagnosed in the first trimester based onabnormal ultrasound scan at 13 weeks gestation whichshowed a severe micrognathia. Regarding the poorprognosis of the syndrome, an early diagnosis is impor-tant for further management of the ongoing pregnancy.

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J Julia Bijok1st Department of Obstetrics & Gynecologyof the Postgraduate Center of Medical EducationCzerniakowska 231, 00-413 Warsaw, Poland e-mail: julia.bijok@gmail.com