A de novo duplication of chromosome 21q22.11→qter associated with Down syndrome: prenatal diagnosis, molecular cytogenetic characterization and fetal ultrasound findings.
OBJECTIVE
To present prenatal diagnosis and molecular cytogenetic characterization of de novo partial partial trisomy 21q (21q22.11→qter) associated with clinodactyly and hypoplastic midphalanx of the fifth fingers, midface hypoplasia, and an intracardiac echogenic focus on prenatal ultrasound.


RESULTS
A 34-year-old gravida 2, para 1 woman underwent amniocentesis at 20 weeks of gestation because of fetal structural abnormalities on prenatal ultrasound. A level II ultrasound at 20 weeks of gestation showed polyhydramnios, clinodactyly and hypoplastic midphalanx of the fifth fingers, midface hypoplasia, and an intracardiac echogenic focus. Amniocentesis revealed an aberrant derivative chromosome 9, or der(9). Parental karyotypes were normal. Spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) analyses revealed that the der(9) contained a segment of chromosome 21 distal to chromosome 9q, and FISH analysis additionally showed that the distal subtelomeric region of 9q was not deleted. Array comparative genomic hybridization (aCGH) demonstrated a 14.8-Mb duplication of distal 21q encompassing the Down syndrome critical region (DSCR) but no genomic imbalance in the distal euchromatic region of chromosome 9. The karyotype was 46,XX,der(9)t(9;21) (q34.3;q22.11)dn. Polymorphic DNA marker analysis revealed the maternal origin of the aberrant chromosome. The pregnancy was subsequently terminated. A malformed female fetus was delivered with a characteristic phenotype of Down syndrome.


CONCLUSIONS
SKY, FISH and aCGH are useful in prenatal investigation of the nature of a de novo aberrant derivative chromosome. Partial trisomy 21q encompassing the DSCR may present characteristic Down syndrome features on prenatal ultrasound.
Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan.
Chih-Ping
CP
Chen
Hsu-Kuang
HK
Huang
Pei-Ying
PY
Ling
Yi-Ning
YN
Su
Ming
M
Chen
Fuu-Jen
FJ
Tsai
Pei-Chen
PC
Wu
Schu-Rern
SR
Chern
Yu-Ting
YT
Chen
Chen-Chi
CC
Lee
Wayseen
W
Wang
D000025:Abortion, Eugenic; D000328:Adult; D000649:Amniocentesis; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D004314:Down Syndrome / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics*; D005260:Female; D005315:Fetal Diseases / Q000175:diagnosis* / Q000235:genetics; D005820:Genetic Testing; D006801:Humans; D011247:Pregnancy; D016216:Ultrasonography, Prenatal