449
Droste et al, Cystic hygroma colli
J. Perinat. Med. 19 (1991) 449-454
Cystic hygroma colli: Perinatal outcome after prenatal diagnosis Sabine Droste1, Susan K. Hendricks2, Holly v. Alfrey2, and Lawrence A. Mack3
Department of Obstetrics and Gynecology, University of Wisconsin, Madison, U.S.A., Departments of Obstetrics and Gynecology, and 3Radiology, University of Washington, Seattle, U.S.A.
1
Introduction
Curriculum vitae
Cystic hygromas are congenital malformations SABINE DROSTE obtained of the lymphatic system, appearing as single or the M. D. degree in 1984. multiloculated fluid filled structures lined by en- A residency in Obstetrics dothelium and containing interstitial lymphoid and Gynecology was folaggregates. They result from a failure of lym- lowed by a perinatal felwhere she trained phatics to connect to the jugular veins at ap- lowship in prenatal diagnosis and proximately 40 days' of embryonic development fetal pathology. As As[13]. This results in distension of the jugular sistant Professor of Oblymphatic sacs and the "jugular lymphatic ob- stetrics and Gynecology struction sequence" [7]. This sequence is char- at the University of Wisacterized by an excess of skin in the neck region consin, her clinical and with altered patterns of their growth and sub- research interests include perinatal genetics, invasive cutaneous lymphedema resulting in hypoconvex prenatal diagnosis, pathologic correlation of prenatal and narrowed nails. In extreme cases, generalized ultrasound findings and the effects of aneuploidy on fetal growth. fetal hydrops may develop. The incidence of nuchal cystic hygroma ranges from as low as 1.2/1000 in spontaneous abor- 2 Materials amd methods tuses [3] to as high as 2.3% at fetal/neonatal autopsy [2]. It may occur as an isolated defect, We reviewed the records of 34 cases of cystic or as either an isolated or syndromically asso- hygroma colli which had been prenatally diagciated autosomal dominant or recessive malfor- nosed by fetal sonography. The patient cohort mation [5]. However, its most frequent associa- consisted of patients referred to the University tion is with fetal aneuploidy [3, 11]. A variety of of Washington Perinatal Center for the evaluakaryotype distributions have been observed, al- tion of a fetal nuchal mass, and of patients in though monosomy X is the classic karyotype whom the cystic hygromas were an incidental thought to be associated with the jugular lym- sonographic finding. All sonograms were iniphatic obstruction sequence [7]. tially read by an attending radiologist and subBecause the strong association with fetal aneu- sequently reviewed by a perinatologist. ploidy frequently results in a decision to termi- A fetal autopsy was obtained on all stillborn or nate the pregnancy electively, information on the terminated fetuses delivering at the University of natural history of this malformation is quite lim- Washington. First and second trimester speciited [5]. The goal of the present report is to mens underwent autopsy in the Central Labocharacterize the karyotype distribution and the ratory for Human Embryology, while larger perinatal outcome in a cohort of fetuses pre- specimens were studied by the Department of natally diagnosed with cystic hygroma colli at a Pathology. All autopsy records were reviewed by Brought to you by | Michigan State University perinatal referral center. a perinatologist. 1991 by Walter de Gruyter & Co. Berlin · New York
Authenticated Download Date | 7/5/15 3:29 AM
450
Droste et al, Cystic hygroma colli
The fetal karyotype was ascertained either from the hospital chart or through the department's computerized prenatal diagnosis database. Whenever the patient's chart was uninformative, information about pregnancy outcome was elicited through direct telephone contact with the referring physician or institution.
3 Results A total of 34 cases of cystic hygroma colli were reviewed. The mean fetal gestational age at diagnosis was 17.3 ± 3.4 weeks (range: 12 — 27 weeks).
Table I. Sonographic and autopsy findings Karyotype
US Findings
Additional autopsy findings
1 2 3 4 5 6 7
46 XX 45 X, inv 9 q 47 XX + 21 — 46 XY (female) —
confirm confirm confirm — small chest, undescended testes hypoplastic lungs horseshoe kidneys
8 9 10
(male) 46 XX 47 XY + 18
11 12
— 45 X
13 14 15
45 X 46 XX 46 XX
hydrops hydrops none hydrops hydrops hydrops cystic dilation of 4th ventricle hydrops none hydrops, choroid plexus cysts anencephaly hydrops, intracardiac mass hydrops hydrops hydrops
16 17 18
46XX, 4p— 46 XX 13q-
hydrops hydrops none
19 20
— —
21 22 23 24 25 26 27 28
45 X — 45 X (female) 47 XY, + 21 45 X 45 X 47 XX + 21
29 30 31 32
47 XY + 21 — 45 X 47 XX, + 13
33
45 X
34
45 X
hydrops hydrops, hypoplastic L heart, common atrium — small kidneys confirm hydrops, short femurs incomplete lung lobation hydrops confirm hydrops — hydrops hydrops, renal agenesis — VSD, truncus arteriosus none confirm dextrocardia, single chambered heart — LS meningomyelocele, polydactyly hydrops hydrops hydrops, lemon sign unilateral renal agenesis hydrops, bilateral hydronephrosis hydrops — | Michigan State University Brought to you by
Case
urethral atresia confirm radial aplasia, clinodactyly, single umbilical artery renal agenesis, phycomelia truncus arteriosus, LV hypoplasia pericardial fibrosis single umbilical artery asplenia, shield chest, streak gonads paratracheal hemangioma, hypoplastic lungs, polysplenia, retrohepatic colon — confirm cleft palate, oligodactyly, overriding aorta, abnormal R renal artery confirm confirm
Authenticated Download Date | 7/5/15 3:29 AM
J. Perinat. Med. 19 (1991)
451
Droste et al, Cystic hygroma colli 3.1
3.3
Sonographic and autopsy findings
Hydrops fetalis was present in 25/34 cases (74%). Additional structural defects were detected sonographically in 11/34 fetuses (32%). Autopsy confirmed the sonographic impression in 10/26 cases (38%) and provided additional information in the remaining 16 cases (62%). In 9 cases (35%) additional structural anomalies were found on autopsy which should have been visible on prenatal sonography but had in fact been missed (cases 7,10,11,12,13,18, 29, 32 and 33; table I). 3.2
Karyotype distribution
Cytogenetic information was available for 23/34 fetuses (68%). While monosomy X was the single most common abnormal karyotype (N = 9), a variety of other abnormal karyotypes collectively accounted for an almost equal proportion of cases (N = 8). Table II summarizes the karyotype distribution of this cohort of fetuses and compares them to the karyotypes noted in a recent review of prenatally diagnosed cystic hygromas.
Perinatal outcome
Outcome data was available for 31 cases (91%). Sicteen patients elected to terminate the pregnancy. The majority of pregnancy terminations occurred in the chromosomally abnormal group of fetuses. The spontaneous perinatal outcome was known for the remaining 17 pregnancies. While spontaneous pregnancy losses were equally divided between abortions and stillbirths, they occurred later in the group of fetuses with normal karyotypes. This observation is statistically significant (Chi square p < 0.01). Both fetuses surviving to live births had an abnormal karyotype (trisomy 21 and monosomy X; table III). Perinatal outcome data was available for 22 of the 25 hydropic fetuses. Hydrops was present in 12 of 15 spontaneous losses (80%). No hydropic fetus survived (table IV). Associated structural anomalies seen on prenatal ultrasound were present in the majority of elective pregnancy terminations, but absent in the most of the spontaneous pregnancy losses (table V). Only one fetus with associated structural
Table Π. Karyotype distribution Karyotype
N
% (of known)
% (of total)
PIJPERS et al., 1988 o/o (N = 84)
Unknown Monosomy Χ Other abnormal Trisomy 21 Trisomy 13 Trisomy 18 Other: 46 XX, 4p46 XX, 13qNormal
11 7 8 4 1 1 2 1 1 5
43 35 17 4 4 8 4 4 24
32 30 24 12 3 3 5 3 3 15
20 46 13 5 6 2 20
Table m. Perinatal outcome by Karyotype Karyotype Normal Abnormal 45 X Other Unknown Total J. Perinat. Med. 19 (1991)
VTOP 1 9 6 3 4
SAB
Stillbirth
Live birth
Survivors
0 5 2 3 3
3 1 1 0 3
9 2 1 1 0
0 1 1 0 0
14 (45%) 8 (25%) 7 (22%) (6%) 1 (3%) Brought to you2by | Michigan State University Authenticated Download Date | 7/5/15 3:29 AM
452
Droste et al, Cystic hygroma colli
Table IV. Outcome by presence or absence of hydrops Anomalies
VTOP
Present Absent
10 4
Total
14
SAB
Stillbirth
Live birth
Survivors
Table V. Outcome by presence or absence of associated structural anomalies on ultrasound Anomalies Present Absent Total
VTOP 9 5
SAB
Stillbirth
Live birth
Survivors
1 7
1 6
1 1
0 1
14
anomalies was liveborn (case 29, table I). In this Down syndrome fetus the cystic hygroma, which had initially been diagnosed at 14.5 weeks' gestation, spontaneously resolved by 20 weeks, but the fetus eventually succumbed to his congenital heart disease. The only long-term survivor, was a Turner syndrome infant without hydrops or other significant structural anomalies (case 21, table I).
Our rate of fetal autopsy was high. In the majority of cases, additional structural malformations were identified. These included a substantial number of malformations which could have been visible on prenatal sonography. In view of the association of cystic hygroma with a number of dominantly or recessively inherited conditions [5], the importance of a careful search for associated anomalies in the postmortem specimen cannot be overemphasized.
4 Discussion
Cystic hygroma colli was associated with a very poor perinatal prognosis. This is in agreement with other recent series [1, 8]. The presence of associated nonimmune hydrops fetalis universally resulted in loss of the pregnancy. MIABARA et al. [10] have speculated that a disorder of neural crest cell migration and abnormal distribution of extracellular matrix may result in a generalized disorder of lymphatic vessel formation and may also account for the high prevalence of cardiovascular defects seen in association with cystic hygromas. It is unknown whether these fetuses with generalized disorders of lymphatic drainage are in fact the ones destined to develop hydrops fetalis.
Our study presents data on one of the largest reported series of prenatally diagnosed cystic hygroma colli from a single institution. As is true for most other series, a large proportion of patients elected to terminate their pregnancy thus limiting the number of patients in whom spontaneous perinatal outcome could be ascertained. However, to our knowledge, only GEMBRUCH et al. [6] have reported the spontaneous perinatal outcome in a larger number of fetuses from a single series. The karyotype distribution in this series is similar to the distribution reported in EDWARDS' and GRAHAM'S recent excellent review [5], although a 4p-karyotype has, to our knowledge, not been reported before.
In our series, the ultimate prognosis appeared to be independent of the fetal karyotype, although pregnancy loss appeared to occur somewhat later Associated structural anomalies were seen on in fetuses with normal karyotypes. Both liveultrasound in a large proportion of fetuses. The borns had abnormal karyotypes, but it is of note fact that this subset of fetuses also accounted for that in the Down syndrome fetus, the cystic the majority of elective pregnancy terminations hygroma spontaneously resolved during the secmay be explained by the high prevalence of aneu- ond trimester. Similar resolution of this malforBrought tomation you by | Michigan University has beenState reported in another fetus with ploidy in this group. Authenticated Download Date | 7/5/15 3:29 AM
J. Perinat. Med. 19 (1991)
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Droste et al, Cystic hygroma colli
Down syndrome [2] and a chromosomally normal fetus [9]. This observation raises the possibility that the timing of the lymphatic connection to venous channels may be disturbed in certain aneuploid conditions, or, alternately, that it may normally be more variable than has previously been thought. With the increasing use of transvaginal high resolution sonography, more cases of spontaneous resolution of nuchal edema/cystic hygroma are already being found (HOLZGREVE W, personal communication, 1990). The outlook in these cases may well be quite different from the poor prognosis which is associated with
this lesion when the diagnosis is made during the second trimester. The present series suggests that cystic hygroma colli diagnosed after 14 weeks' gestation is an almost universally lethal malformation. Neither a normal karoyotype nor the absence of associated fetal structural anomalies on ultrasound appear to improve this grim prognosis. At our institution, pregnancy termination may have been more liberally applied to chromosomally abnormal fetuses. In view of these data, however, this counselling practice may need to be reexamined.
Abstract Prenatally diagnosed cystic hygroma colli is associated with Turner syndrome, but has been reported with a variety of other conditions. The association with abnormal karyotypes frequently results in a decision to terminate the pregnancy. Information on the natural history of this malformation is thus limited. We reviewed 34 cases of cystic hygroma colli which were diagnosed by ultrasound at a mean gestational age of 17.3 + 3.4 weeks. Pregnancy outcome was known for 31 of these cases. The distribution of fetal karyotypes, available for 23 fetuses, was similar to that reported in other series. Only two fetuses, both with an abnormal karyotype, were liveborn at term. Fourteen pregnancies were electively terminated while the remaining
15 cases resulted in spontaneous pregnancy loss. Twenty-six fetuses underwent necropsy which generally confirmed the prenatal ultrasound findings. However, in 9 cases associated anomalies had been missed by the sonogram. Only one fetus with associated anomalies survived to term. Hydrops was common and occurred in most of the spontaneous losses. This series suggests that the prenatal finding of cystic hygroma colli portends an extremely poor prognosis regardless of the karyotype or the presence or nature of associated anomalies. We confirm that karyotypes other than monosomy X are common and that perinatal survival is highly unlikely, especially in the presence of hydrops fetalis.
Keywords: Cystic hygroma, karyotype distribution, perinatal outcome.
Zusammenfassung Cystisches Hygroma colli: Perinatales Outcome nach pränataler Diagnose Über den Krankheitsverlauf beim cystischen Hygroma colli gibt es nur wenige Informationen, weil es in Assoziation mit einem anormalen Karyotyp auftritt und somit häufig ein Schwangerschaftsabbruch vorgenommen wird. Wir versuchten, die Verteilung der Karyotypen und das perinatale Outcome bei Feten, wo pränatal ein cystisches Hygroma colli diagnostiziert worden war, zu erfassen, wobei wir uns auf nur ein perinatales Zentrum beziehen. Analysiert wurden die Aufzeichnungen von 34 Fällen mit cystischem Hygroma colli; die sonografische Diagnose erfolgt mit 17.3 ± 3.4 Schwangerschaftswochen. Bei 31 Fällen war eine abschließende Beurteilung des Verlaufes möglich. 2 Feten mit anormalem Karyotyp wurden am Termin lebendgeboren, 14 Schwangeschaften wurden abgebrochen und in den verbleibenden 15 Fällen kam es zum Spontanabort. Bei 26 Feten wurden Obduktionen vorge-
nommen, weobei die pränatale sonografische Diagnose bestätigt wurde, aber in der Mehrzahl der Fälle noch zusätzliche Informationen geliefert werden konnten. Lediglich ein Fet mit zusätzlichen Anomalien überlebte bis zum Termin. In 23 Fällen lagen cytogenetische Daten vor. In der Mehrzahl der Fälle, darunter in der überwiegenden Anzahl der Spontanaborte, lag ein Hydrops vor. Die beiden Lebendgeburten am Termin hatten keinen Hydrops. Wir schließen aus unseren Untersuchungen, daß der pränatale Befund eines cystischen Hygroma colli, unabhängig vom fetalen Karyotyp und dem Vorhandensein oder der Art der assoziierten Mißbildungen mit einer sehr schlechten Prognose gleichzusetzen ist. Besonders bei Vorliegen eines Hydrops fetalis ist die Überlebenswahrscheinlichkeit gering. Alle Feten mit einem cystischen Hygrom sollten obduziert werden, um weitere assoziierte, strukturelle Mißbildungen aufzudecken.
Broughtperinatales to you by | Outcome. Michigan State University Schlüsselwörter: Cystisches Hygrom, Karyotypverteilung, J. Perinat. Med. 19 (1991)
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Droste et al, Cystic hygroma colli
Resume Hygroma cervical kystique: Devenir perinatal apres diagnostic prenatal
Les informations sur l'histoire naturelle des hygromas kystiques du cou sont limitees, du fait de leur association avec des caryotypes anormauy, qui conduisent, frequemment, ä la decision d'interrompre la grossesse. Nous avons essaye de carracterise la distribution des caryotypes et le devenir perinatal, pour une cohorte de foetus, chez lesquels un diagnostic prenatal d'hygroma kystique du cou a etc porte, dans un unique centre de reference perinatal. On a revu les dossiers de 34 cas d'hygromas kystiques du cou, diagnostiques par echographie ä 17,3 + ou — 3,4 semaines. Devolution de la grossesse est connue pour 31 de ces cas. Deux foetus, avec un caryotype anormal, ont ete vivants a terme, 14 grossesses ont ete interrompues, et les 15 cas restants ont evolue vers une interruption spontanee de la grossesse. 26 foetus ont eu une autopsie, qui a ge-
nerallement conflrme les donnees echographiques prenatales, mais qui a egalement fournit des informations supplementaires dans la majorite des cas. Un seul foetus, porteur d'anomalies associees, a survecu jusqu'au terme.On dispose d'informations cytogenetiques pour 23 cas. Pour la majorite des foetus, un hydrops est survenu, egalement pour la pluspart des avortements spontanes. Les deux foetus, nes ä terme, n'etaient pas hydropiques. Nous en concluons que lese donnees prenatales des hygromas kystiques du cou ne fournissent qu'un tres mediocre pronostic, en comparaison du caryotype foetal ou de la presence et de la nature des anomalies associees. la survie perinatale est particulierement peu probable en presence d'hydrops foetalis. Tous les foetus porteurs d'un hygroma kystique devraient subir une autopsie perinatale soigneuse, ä la recherche d'anomalies structurales associees.
Mots-cles: Devenir perinatal, distribution des caryotypes, hygroma kystique.
References
[1] ABRAMOWICZ JS, SL WARSOF, D LOCHNER-DOYLE et al.: Congenital cystic hygroma of the neck diagnosed prenatally: outcome with normal and abnormal karyotype. Prenat Diag 9 (1989) 321 [2] BARR JM: Fetal cystic hygromas: Turner syndrome and other causes. Proc Greenwood Genetics Center 4 (1985) 88 [3] BRONSHTEIN M, S ROTTEM, N YEFFE et al.: First trimester and early second trimester diagnosis of nuchal cystic hygroma by transvaginal sonography: Diverse prognosis of the septated from the nonseptated lesion. Am J Obstet Gynecol 151 (1989) 78 [4] COHEN MM, S SCHWARTZ, MF SCHWARTZ et al.: Antenatal detection of cystic hygroma. Obstet Gynecol Surv 44 (1989) 481 [5] EDWARDS MJ, JM GRAHAM: Posterior nuchal cystic hygroma. Clin Perinatol 17 (1990) 611 [6] GEMBRUCH U, M HANSMANN, R BALD et al.: Prenatal diagnosis and management in fetuses with cystic hygroma colli. Eur J Obstet Gynecol Reprod Biol 29 (1988) 241 [7] JONES KL (ed): Smith's recognizable patterns of human malformation. Saunders, Philadelphia— London 1988 [8] LANGER JC, PG FITZGERALD, D DESA et al.: Cervical cystic hygroma in the fetus: clinical spectrum and outcome. J Pediatr Surg 15 (1990) 58
[9] MACKEN MB, EB GRANTMYRE, MJ VINCER: Regression of nuchal cystic hygroma in utero. J Ultrasound Med 8 (1989) 101 [10] MlYABARA S, H SUGfflARA, N MAEHARA et al.I
Significance of cardiovascular malformations in cystic hygroma: a new interpretation of the pathogenesis. Am J Med Genet 34 (1989) 489 [11] PIJPERS L, A REUSS, PA STEWART: Cervical cystic hygroma: prenatal diagnosis and management. Obstet Gynecol 72 (1988) 223 [12] RODIS JF, AM VINTZILEOS, WA CAMPBELL, D NOCHIMSON: Spontaneous resoltuion of fetal cystic hygroma in Down's syndrome. Obstet Gynecol 71 (1988) 976 [13] VAN DER PUTTE SCJ: Lymphatic malformations in human fetuses. Virchow's Arch [path, anat.] 376 (1977) 233 Received and accepted May 5, 1991. Sabine Droste, M. D. University of Wisconsin Department of Obstetrics and Gynecology Division of Perinatal Medicine / Meriter/Madison General Hospital 202 South Park Street Madison, WI 53715 U.S.A.
Brought to you by | Michigan State University Authenticated Download Date | 7/5/15 3:29 AM J. Perinat. Med. 19 (1991)
Droste et al, Cystic hygroma colli
J. Perinat. Med. 19 (1991) 449-454
Cystic hygroma colli: Perinatal outcome after prenatal diagnosis Sabine Droste1, Susan K. Hendricks2, Holly v. Alfrey2, and Lawrence A. Mack3
Department of Obstetrics and Gynecology, University of Wisconsin, Madison, U.S.A., Departments of Obstetrics and Gynecology, and 3Radiology, University of Washington, Seattle, U.S.A.
1
Introduction
Curriculum vitae
Cystic hygromas are congenital malformations SABINE DROSTE obtained of the lymphatic system, appearing as single or the M. D. degree in 1984. multiloculated fluid filled structures lined by en- A residency in Obstetrics dothelium and containing interstitial lymphoid and Gynecology was folaggregates. They result from a failure of lym- lowed by a perinatal felwhere she trained phatics to connect to the jugular veins at ap- lowship in prenatal diagnosis and proximately 40 days' of embryonic development fetal pathology. As As[13]. This results in distension of the jugular sistant Professor of Oblymphatic sacs and the "jugular lymphatic ob- stetrics and Gynecology struction sequence" [7]. This sequence is char- at the University of Wisacterized by an excess of skin in the neck region consin, her clinical and with altered patterns of their growth and sub- research interests include perinatal genetics, invasive cutaneous lymphedema resulting in hypoconvex prenatal diagnosis, pathologic correlation of prenatal and narrowed nails. In extreme cases, generalized ultrasound findings and the effects of aneuploidy on fetal growth. fetal hydrops may develop. The incidence of nuchal cystic hygroma ranges from as low as 1.2/1000 in spontaneous abor- 2 Materials amd methods tuses [3] to as high as 2.3% at fetal/neonatal autopsy [2]. It may occur as an isolated defect, We reviewed the records of 34 cases of cystic or as either an isolated or syndromically asso- hygroma colli which had been prenatally diagciated autosomal dominant or recessive malfor- nosed by fetal sonography. The patient cohort mation [5]. However, its most frequent associa- consisted of patients referred to the University tion is with fetal aneuploidy [3, 11]. A variety of of Washington Perinatal Center for the evaluakaryotype distributions have been observed, al- tion of a fetal nuchal mass, and of patients in though monosomy X is the classic karyotype whom the cystic hygromas were an incidental thought to be associated with the jugular lym- sonographic finding. All sonograms were iniphatic obstruction sequence [7]. tially read by an attending radiologist and subBecause the strong association with fetal aneu- sequently reviewed by a perinatologist. ploidy frequently results in a decision to termi- A fetal autopsy was obtained on all stillborn or nate the pregnancy electively, information on the terminated fetuses delivering at the University of natural history of this malformation is quite lim- Washington. First and second trimester speciited [5]. The goal of the present report is to mens underwent autopsy in the Central Labocharacterize the karyotype distribution and the ratory for Human Embryology, while larger perinatal outcome in a cohort of fetuses pre- specimens were studied by the Department of natally diagnosed with cystic hygroma colli at a Pathology. All autopsy records were reviewed by Brought to you by | Michigan State University perinatal referral center. a perinatologist. 1991 by Walter de Gruyter & Co. Berlin · New York
Authenticated Download Date | 7/5/15 3:29 AM
450
Droste et al, Cystic hygroma colli
The fetal karyotype was ascertained either from the hospital chart or through the department's computerized prenatal diagnosis database. Whenever the patient's chart was uninformative, information about pregnancy outcome was elicited through direct telephone contact with the referring physician or institution.
3 Results A total of 34 cases of cystic hygroma colli were reviewed. The mean fetal gestational age at diagnosis was 17.3 ± 3.4 weeks (range: 12 — 27 weeks).
Table I. Sonographic and autopsy findings Karyotype
US Findings
Additional autopsy findings
1 2 3 4 5 6 7
46 XX 45 X, inv 9 q 47 XX + 21 — 46 XY (female) —
confirm confirm confirm — small chest, undescended testes hypoplastic lungs horseshoe kidneys
8 9 10
(male) 46 XX 47 XY + 18
11 12
— 45 X
13 14 15
45 X 46 XX 46 XX
hydrops hydrops none hydrops hydrops hydrops cystic dilation of 4th ventricle hydrops none hydrops, choroid plexus cysts anencephaly hydrops, intracardiac mass hydrops hydrops hydrops
16 17 18
46XX, 4p— 46 XX 13q-
hydrops hydrops none
19 20
— —
21 22 23 24 25 26 27 28
45 X — 45 X (female) 47 XY, + 21 45 X 45 X 47 XX + 21
29 30 31 32
47 XY + 21 — 45 X 47 XX, + 13
33
45 X
34
45 X
hydrops hydrops, hypoplastic L heart, common atrium — small kidneys confirm hydrops, short femurs incomplete lung lobation hydrops confirm hydrops — hydrops hydrops, renal agenesis — VSD, truncus arteriosus none confirm dextrocardia, single chambered heart — LS meningomyelocele, polydactyly hydrops hydrops hydrops, lemon sign unilateral renal agenesis hydrops, bilateral hydronephrosis hydrops — | Michigan State University Brought to you by
Case
urethral atresia confirm radial aplasia, clinodactyly, single umbilical artery renal agenesis, phycomelia truncus arteriosus, LV hypoplasia pericardial fibrosis single umbilical artery asplenia, shield chest, streak gonads paratracheal hemangioma, hypoplastic lungs, polysplenia, retrohepatic colon — confirm cleft palate, oligodactyly, overriding aorta, abnormal R renal artery confirm confirm
Authenticated Download Date | 7/5/15 3:29 AM
J. Perinat. Med. 19 (1991)
451
Droste et al, Cystic hygroma colli 3.1
3.3
Sonographic and autopsy findings
Hydrops fetalis was present in 25/34 cases (74%). Additional structural defects were detected sonographically in 11/34 fetuses (32%). Autopsy confirmed the sonographic impression in 10/26 cases (38%) and provided additional information in the remaining 16 cases (62%). In 9 cases (35%) additional structural anomalies were found on autopsy which should have been visible on prenatal sonography but had in fact been missed (cases 7,10,11,12,13,18, 29, 32 and 33; table I). 3.2
Karyotype distribution
Cytogenetic information was available for 23/34 fetuses (68%). While monosomy X was the single most common abnormal karyotype (N = 9), a variety of other abnormal karyotypes collectively accounted for an almost equal proportion of cases (N = 8). Table II summarizes the karyotype distribution of this cohort of fetuses and compares them to the karyotypes noted in a recent review of prenatally diagnosed cystic hygromas.
Perinatal outcome
Outcome data was available for 31 cases (91%). Sicteen patients elected to terminate the pregnancy. The majority of pregnancy terminations occurred in the chromosomally abnormal group of fetuses. The spontaneous perinatal outcome was known for the remaining 17 pregnancies. While spontaneous pregnancy losses were equally divided between abortions and stillbirths, they occurred later in the group of fetuses with normal karyotypes. This observation is statistically significant (Chi square p < 0.01). Both fetuses surviving to live births had an abnormal karyotype (trisomy 21 and monosomy X; table III). Perinatal outcome data was available for 22 of the 25 hydropic fetuses. Hydrops was present in 12 of 15 spontaneous losses (80%). No hydropic fetus survived (table IV). Associated structural anomalies seen on prenatal ultrasound were present in the majority of elective pregnancy terminations, but absent in the most of the spontaneous pregnancy losses (table V). Only one fetus with associated structural
Table Π. Karyotype distribution Karyotype
N
% (of known)
% (of total)
PIJPERS et al., 1988 o/o (N = 84)
Unknown Monosomy Χ Other abnormal Trisomy 21 Trisomy 13 Trisomy 18 Other: 46 XX, 4p46 XX, 13qNormal
11 7 8 4 1 1 2 1 1 5
43 35 17 4 4 8 4 4 24
32 30 24 12 3 3 5 3 3 15
20 46 13 5 6 2 20
Table m. Perinatal outcome by Karyotype Karyotype Normal Abnormal 45 X Other Unknown Total J. Perinat. Med. 19 (1991)
VTOP 1 9 6 3 4
SAB
Stillbirth
Live birth
Survivors
0 5 2 3 3
3 1 1 0 3
9 2 1 1 0
0 1 1 0 0
14 (45%) 8 (25%) 7 (22%) (6%) 1 (3%) Brought to you2by | Michigan State University Authenticated Download Date | 7/5/15 3:29 AM
452
Droste et al, Cystic hygroma colli
Table IV. Outcome by presence or absence of hydrops Anomalies
VTOP
Present Absent
10 4
Total
14
SAB
Stillbirth
Live birth
Survivors
Table V. Outcome by presence or absence of associated structural anomalies on ultrasound Anomalies Present Absent Total
VTOP 9 5
SAB
Stillbirth
Live birth
Survivors
1 7
1 6
1 1
0 1
14
anomalies was liveborn (case 29, table I). In this Down syndrome fetus the cystic hygroma, which had initially been diagnosed at 14.5 weeks' gestation, spontaneously resolved by 20 weeks, but the fetus eventually succumbed to his congenital heart disease. The only long-term survivor, was a Turner syndrome infant without hydrops or other significant structural anomalies (case 21, table I).
Our rate of fetal autopsy was high. In the majority of cases, additional structural malformations were identified. These included a substantial number of malformations which could have been visible on prenatal sonography. In view of the association of cystic hygroma with a number of dominantly or recessively inherited conditions [5], the importance of a careful search for associated anomalies in the postmortem specimen cannot be overemphasized.
4 Discussion
Cystic hygroma colli was associated with a very poor perinatal prognosis. This is in agreement with other recent series [1, 8]. The presence of associated nonimmune hydrops fetalis universally resulted in loss of the pregnancy. MIABARA et al. [10] have speculated that a disorder of neural crest cell migration and abnormal distribution of extracellular matrix may result in a generalized disorder of lymphatic vessel formation and may also account for the high prevalence of cardiovascular defects seen in association with cystic hygromas. It is unknown whether these fetuses with generalized disorders of lymphatic drainage are in fact the ones destined to develop hydrops fetalis.
Our study presents data on one of the largest reported series of prenatally diagnosed cystic hygroma colli from a single institution. As is true for most other series, a large proportion of patients elected to terminate their pregnancy thus limiting the number of patients in whom spontaneous perinatal outcome could be ascertained. However, to our knowledge, only GEMBRUCH et al. [6] have reported the spontaneous perinatal outcome in a larger number of fetuses from a single series. The karyotype distribution in this series is similar to the distribution reported in EDWARDS' and GRAHAM'S recent excellent review [5], although a 4p-karyotype has, to our knowledge, not been reported before.
In our series, the ultimate prognosis appeared to be independent of the fetal karyotype, although pregnancy loss appeared to occur somewhat later Associated structural anomalies were seen on in fetuses with normal karyotypes. Both liveultrasound in a large proportion of fetuses. The borns had abnormal karyotypes, but it is of note fact that this subset of fetuses also accounted for that in the Down syndrome fetus, the cystic the majority of elective pregnancy terminations hygroma spontaneously resolved during the secmay be explained by the high prevalence of aneu- ond trimester. Similar resolution of this malforBrought tomation you by | Michigan University has beenState reported in another fetus with ploidy in this group. Authenticated Download Date | 7/5/15 3:29 AM
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Down syndrome [2] and a chromosomally normal fetus [9]. This observation raises the possibility that the timing of the lymphatic connection to venous channels may be disturbed in certain aneuploid conditions, or, alternately, that it may normally be more variable than has previously been thought. With the increasing use of transvaginal high resolution sonography, more cases of spontaneous resolution of nuchal edema/cystic hygroma are already being found (HOLZGREVE W, personal communication, 1990). The outlook in these cases may well be quite different from the poor prognosis which is associated with
this lesion when the diagnosis is made during the second trimester. The present series suggests that cystic hygroma colli diagnosed after 14 weeks' gestation is an almost universally lethal malformation. Neither a normal karoyotype nor the absence of associated fetal structural anomalies on ultrasound appear to improve this grim prognosis. At our institution, pregnancy termination may have been more liberally applied to chromosomally abnormal fetuses. In view of these data, however, this counselling practice may need to be reexamined.
Abstract Prenatally diagnosed cystic hygroma colli is associated with Turner syndrome, but has been reported with a variety of other conditions. The association with abnormal karyotypes frequently results in a decision to terminate the pregnancy. Information on the natural history of this malformation is thus limited. We reviewed 34 cases of cystic hygroma colli which were diagnosed by ultrasound at a mean gestational age of 17.3 + 3.4 weeks. Pregnancy outcome was known for 31 of these cases. The distribution of fetal karyotypes, available for 23 fetuses, was similar to that reported in other series. Only two fetuses, both with an abnormal karyotype, were liveborn at term. Fourteen pregnancies were electively terminated while the remaining
15 cases resulted in spontaneous pregnancy loss. Twenty-six fetuses underwent necropsy which generally confirmed the prenatal ultrasound findings. However, in 9 cases associated anomalies had been missed by the sonogram. Only one fetus with associated anomalies survived to term. Hydrops was common and occurred in most of the spontaneous losses. This series suggests that the prenatal finding of cystic hygroma colli portends an extremely poor prognosis regardless of the karyotype or the presence or nature of associated anomalies. We confirm that karyotypes other than monosomy X are common and that perinatal survival is highly unlikely, especially in the presence of hydrops fetalis.
Keywords: Cystic hygroma, karyotype distribution, perinatal outcome.
Zusammenfassung Cystisches Hygroma colli: Perinatales Outcome nach pränataler Diagnose Über den Krankheitsverlauf beim cystischen Hygroma colli gibt es nur wenige Informationen, weil es in Assoziation mit einem anormalen Karyotyp auftritt und somit häufig ein Schwangerschaftsabbruch vorgenommen wird. Wir versuchten, die Verteilung der Karyotypen und das perinatale Outcome bei Feten, wo pränatal ein cystisches Hygroma colli diagnostiziert worden war, zu erfassen, wobei wir uns auf nur ein perinatales Zentrum beziehen. Analysiert wurden die Aufzeichnungen von 34 Fällen mit cystischem Hygroma colli; die sonografische Diagnose erfolgt mit 17.3 ± 3.4 Schwangerschaftswochen. Bei 31 Fällen war eine abschließende Beurteilung des Verlaufes möglich. 2 Feten mit anormalem Karyotyp wurden am Termin lebendgeboren, 14 Schwangeschaften wurden abgebrochen und in den verbleibenden 15 Fällen kam es zum Spontanabort. Bei 26 Feten wurden Obduktionen vorge-
nommen, weobei die pränatale sonografische Diagnose bestätigt wurde, aber in der Mehrzahl der Fälle noch zusätzliche Informationen geliefert werden konnten. Lediglich ein Fet mit zusätzlichen Anomalien überlebte bis zum Termin. In 23 Fällen lagen cytogenetische Daten vor. In der Mehrzahl der Fälle, darunter in der überwiegenden Anzahl der Spontanaborte, lag ein Hydrops vor. Die beiden Lebendgeburten am Termin hatten keinen Hydrops. Wir schließen aus unseren Untersuchungen, daß der pränatale Befund eines cystischen Hygroma colli, unabhängig vom fetalen Karyotyp und dem Vorhandensein oder der Art der assoziierten Mißbildungen mit einer sehr schlechten Prognose gleichzusetzen ist. Besonders bei Vorliegen eines Hydrops fetalis ist die Überlebenswahrscheinlichkeit gering. Alle Feten mit einem cystischen Hygrom sollten obduziert werden, um weitere assoziierte, strukturelle Mißbildungen aufzudecken.
Broughtperinatales to you by | Outcome. Michigan State University Schlüsselwörter: Cystisches Hygrom, Karyotypverteilung, J. Perinat. Med. 19 (1991)
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Resume Hygroma cervical kystique: Devenir perinatal apres diagnostic prenatal
Les informations sur l'histoire naturelle des hygromas kystiques du cou sont limitees, du fait de leur association avec des caryotypes anormauy, qui conduisent, frequemment, ä la decision d'interrompre la grossesse. Nous avons essaye de carracterise la distribution des caryotypes et le devenir perinatal, pour une cohorte de foetus, chez lesquels un diagnostic prenatal d'hygroma kystique du cou a etc porte, dans un unique centre de reference perinatal. On a revu les dossiers de 34 cas d'hygromas kystiques du cou, diagnostiques par echographie ä 17,3 + ou — 3,4 semaines. Devolution de la grossesse est connue pour 31 de ces cas. Deux foetus, avec un caryotype anormal, ont ete vivants a terme, 14 grossesses ont ete interrompues, et les 15 cas restants ont evolue vers une interruption spontanee de la grossesse. 26 foetus ont eu une autopsie, qui a ge-
nerallement conflrme les donnees echographiques prenatales, mais qui a egalement fournit des informations supplementaires dans la majorite des cas. Un seul foetus, porteur d'anomalies associees, a survecu jusqu'au terme.On dispose d'informations cytogenetiques pour 23 cas. Pour la majorite des foetus, un hydrops est survenu, egalement pour la pluspart des avortements spontanes. Les deux foetus, nes ä terme, n'etaient pas hydropiques. Nous en concluons que lese donnees prenatales des hygromas kystiques du cou ne fournissent qu'un tres mediocre pronostic, en comparaison du caryotype foetal ou de la presence et de la nature des anomalies associees. la survie perinatale est particulierement peu probable en presence d'hydrops foetalis. Tous les foetus porteurs d'un hygroma kystique devraient subir une autopsie perinatale soigneuse, ä la recherche d'anomalies structurales associees.
Mots-cles: Devenir perinatal, distribution des caryotypes, hygroma kystique.
References
[1] ABRAMOWICZ JS, SL WARSOF, D LOCHNER-DOYLE et al.: Congenital cystic hygroma of the neck diagnosed prenatally: outcome with normal and abnormal karyotype. Prenat Diag 9 (1989) 321 [2] BARR JM: Fetal cystic hygromas: Turner syndrome and other causes. Proc Greenwood Genetics Center 4 (1985) 88 [3] BRONSHTEIN M, S ROTTEM, N YEFFE et al.: First trimester and early second trimester diagnosis of nuchal cystic hygroma by transvaginal sonography: Diverse prognosis of the septated from the nonseptated lesion. Am J Obstet Gynecol 151 (1989) 78 [4] COHEN MM, S SCHWARTZ, MF SCHWARTZ et al.: Antenatal detection of cystic hygroma. Obstet Gynecol Surv 44 (1989) 481 [5] EDWARDS MJ, JM GRAHAM: Posterior nuchal cystic hygroma. Clin Perinatol 17 (1990) 611 [6] GEMBRUCH U, M HANSMANN, R BALD et al.: Prenatal diagnosis and management in fetuses with cystic hygroma colli. Eur J Obstet Gynecol Reprod Biol 29 (1988) 241 [7] JONES KL (ed): Smith's recognizable patterns of human malformation. Saunders, Philadelphia— London 1988 [8] LANGER JC, PG FITZGERALD, D DESA et al.: Cervical cystic hygroma in the fetus: clinical spectrum and outcome. J Pediatr Surg 15 (1990) 58
[9] MACKEN MB, EB GRANTMYRE, MJ VINCER: Regression of nuchal cystic hygroma in utero. J Ultrasound Med 8 (1989) 101 [10] MlYABARA S, H SUGfflARA, N MAEHARA et al.I
Significance of cardiovascular malformations in cystic hygroma: a new interpretation of the pathogenesis. Am J Med Genet 34 (1989) 489 [11] PIJPERS L, A REUSS, PA STEWART: Cervical cystic hygroma: prenatal diagnosis and management. Obstet Gynecol 72 (1988) 223 [12] RODIS JF, AM VINTZILEOS, WA CAMPBELL, D NOCHIMSON: Spontaneous resoltuion of fetal cystic hygroma in Down's syndrome. Obstet Gynecol 71 (1988) 976 [13] VAN DER PUTTE SCJ: Lymphatic malformations in human fetuses. Virchow's Arch [path, anat.] 376 (1977) 233 Received and accepted May 5, 1991. Sabine Droste, M. D. University of Wisconsin Department of Obstetrics and Gynecology Division of Perinatal Medicine / Meriter/Madison General Hospital 202 South Park Street Madison, WI 53715 U.S.A.
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