Clinical, cytogenetic, and molecular findings of prenatally diagnosed mosaic trisomy 4.
OBJECTIVE
To present the clinical, cytogenetic, and molecular findings of prenatally diagnosed mosaic trisomy 4.


METHODS
An amniocentesis was performed at 21 weeks' gestation because of maternal anxiety. Cytogenetic analysis revealed mosaicism for trisomy 4, 47,XX,+4[4]/46,XX[16]. Level II ultrasound demonstrated tetralogy of Fallot. Repeated amniocentesis at 23 weeks' gestation revealed 47,XX,+4[4]/46,XX[19]. The pregnancy was terminated. Phenotypic findings included tetralogy of Fallot, hypertelorism, micrognathia, abnormal ears, duplicated phalanges of the left thumb, clinodactyly, and overlapping of the toes. The karyotype of the cord blood was 46,XX. Cytogenetic analyses of the multiple tissue samplings showed a karyotype of 47,XX,+4 in 40/40 cells of the amniotic membrane (amnion), and 47,XX,+4/46,XX with various levels of trisomy 4 in the cells of the liver, lungs, placenta, skin, and umbilical cord. The levels of trisomy 4 were 11/40 in the liver, 8/40 in the lungs, 31/40 in the placenta, 9/40 in the skin, and 8/40 in the umbilical cord.


METHODS
The parental origin and meiotic origin of trisomy 4 were determined by examining the amniotic membrane using quantitative fluorescent polymerase chain reaction assays with polymorphic markers specific for chromosome 4. The result was consistent with a paternal meiosis I nondisjunction error. The cord blood showed a biparental inheritance. An extra paternal heterozygous allele with partial dosage increase was noted in other fetal and extraembryonic tissues studied.


CONCLUSIONS
A diagnosis of trisomy 4 mosaicism in amniocytes indicates an increased risk for fetal abnormalities. Associated abnormal findings include congenital heart defects and anomalies of the digits and thumb. A confirmatory placental sampling may be helpful, whereas a fetal blood sampling is of a very limited value. A postnatal amnion sampling may provide additional clues to the fetal involvement of trisomy 4.
Chen
Chih-Ping
CP
Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan, Republic of China. cpc_mmh@yahoo.com
Chern
Schu-Rern
SR
Lee
Chen-Chi
CC
Chang
Tung-Yao
TY
Wang
Wayseen
W
Tzen
Chin-Yuan
CY
D000028:Abortion, Induced; D000328:Adult; D000649:Amniocentesis; D002894:Chromosomes, Human, Pair 4; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D009030:Mosaicism / Q000175:diagnosis* / Q000473:pathology; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011296:Prenatal Diagnosis; D014314:Trisomy / Q000175:diagnosis* / Q000473:pathology; D016216:Ultrasonography, Prenatal