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Trisomy 16, once thought to result uniformly in early pregnancy loss, has been detected in chorionic villus samples (CVS) from on-going pregnancies and was initially ascribed to a second, nonviable pregnancy. Prenatally detected trisomy 16 in CVS and its resolution to disomy has led to the reexamination of the viability of trisomy 16. This study evaluates 11 cases of mosaic trisomy 16 detected through second trimester amniocentesis. In 9 of the 11 cases, amniocenteses were performed in women under the age of 35 because of abnormal levels of maternal serum alpha-fetoprotein (MSAFP) or maternal serum human chorionic gonadotropin (MShCG). The other two amniocenteses were performed for advanced maternal age. Five of the 11 pregnancies resulted in liveborn infants, and six pregnancies were electively terminated. The liveborn infants all had some combination of intrauterine growth retardation (IUGR), congenital heart defects (CHD), or minor anomalies. Two of them died neonatally because of complications of severe congenital heart defects. The three surviving children have variable growth retardation, developmental delay, congenital anomalies, and/or minor anomalies. In the terminated pregnancies, the four fetuses evaluated by ultrasound or autopsy demonstrated various congenital anomalies and/or IUGR. Cytogenetic and fluorescent in situ hybridization studies identified true mosaicism in 5 of 10 cases examined, although the abnormal cell line was never seen in more than 1% of cultured lymphocytes. Placental mosaicism was seen in all placentas examined and was associated with IUGR in four of seven cases. Maternal uniparental disomy was identified in three cases. Mosaic trisomy 16 detected through amniocentesis is not a benign finding but associated with a high risk of abnormal outcome, most commonly IUGR, CHD, developmental delay, and minor anomalies. The various outcomes may reflect the diversity of mechanisms involved in the resolution of this abnormality. As 80% of these patients were ascertained because of the presence of abnormal levels of MSAFP or MShCG, the increased use of maternal serum screening should bring more such cases to clinical attention.

Monosomy of the entire short arm of chromosome 18 as a result of an 18;acrocentric whole arm translocation has been reported in over 20 patients, 3 of which were familial. The centromeric origin in de novo cases has not been characterized. We report molecular cytogenetic studies of two prenatally-detected de novo cases. Amniocenteses were performed because of sonographic findings of fetal holoprosencephaly. Cytogenetic studies and dual color fluorescence in situ hybridization using Oncor alpha-satellite probes for D18Z1 and D13Z1/D21Z1 showed monosomy 18p with presence of a dicentric 18;21 chromosome in both cases [45,XY,dic(18;21)(p11.1;p11.1)]. In one case, a second cell line was found, which contained 46 chromosomes with a del(18)(p11.1) and an apparently telocentric 21 not present in either parent [46,XY,del(18)(p11.1),del(21)(p11.1)]. The del(18)(p11.1) contained only the 18 alphoid sequence and the telocentric 21 contained only the 21 alphoid sequence. No centromeric break was detected. We propose that the second cell line arose from dissociation of the dic(18;21) with no centromeric DNA break. In addition to our case, there have been three previous reports of dissociation of dicentric 18;acrocentric chromosomes indicating that the translocation site can be unstable and dissociate.

We report on a 30-year-old women with de novo ring chromosome 12 mosaicism, 46,XX, r(12)(p13.3q24.3)/46,XX. In addition to the clinical manifestations generally observed in "ring syndrome" cases such as growth retardation, short stature, microcephaly, and mental deficiency, she had a broad nasal bridge, micrognathia with overbite, underdeveloped breasts, mild dorsal scoliosis, clinodactyly of the fifth fingers with a single interdigital crease, symphalangism of thumbs, tapering fingers, mild cutaneous syndactyly between the second and third toes, multiple café-au-lait spots, sebaceous acne on the face and back, and mild dystrophic toenails. She developed a large, pedunculated uterine leiomyoma at age 28 years. To our knowledge, uterine leiomyoma in association with r(12) has not been reported previously. However, a gain of chromosome 12 and translocations involving 12q14-15 have been described.