Hum. Genet. 33, 331--334 (1976) © by Springer-Verlag 1976

Tertiary Trisomy, 47, XX, + 14q--, Resulting from Maternal Balanced Translocation, 46, XX, t(14; 16)(q 11 ;q24) S. R o b e r t Y o u n g l, Denis M. D o n o v a n 1, H a r r y A. Greer 1, K a y B u t c h 2, a n d D a v i d C. P o t t e r a i William S. Hall Psychiatric Institute, South Carolina Department of Mental Health, Columbia, South Carolina Department of Obstetrics and Gynecology, Richland Memorial Hospital, Columbia, South Carolina 3 Franklin McLean Memorial Research Institute*, Chicago, Illinois Received December 14, 1975 / April 19, 1976

Summary. A 3-year-old child with tertiary trisomy 14 (q-14q--), daughter of a mother with a balanced reciprocal translocation [46,XX,t(14;16)(qll;@4)] is presented. Craniostenosis and developmental retardation were the primary presenting features in this patient. Introduction F u l l t r i s o m y 14 has been described in a s p o n t a n e o u s a b o r t i o n (Kajii et al., 1972) a n d is claimed in a 2 ~ - y e a r - o l d girl with m u l t i p l e m a l f o r m a t i o n s (Murken et al., 1970). There h a v e been several r e p o r t s of t r i s o m y for t h e s h o r t arms, c e n t r o m e r e a n d one h a l f or m o r e of t h e long arms of 14 (Allderdiee et al., 1971 ; S h o r t et al., 1972; Reiss et al., 1972; L a u r e n t et al., 1973). F r y n s et al. (1974) r e p o r t a 7-year-old girl who is trisomic for j u s t t h e s h o r t arms, e e n t r o m e r e a n d small a m o u n t of p r o x i m a l long a r m of 14. This girl's m o t h e r a p p e a r s t o be a b a l a n c e d carrier of this 14q c h r o m o s o m e a n d a 14/19 t r a n s l o c a t i o n chromosome. There is one r e p o r t of a t r i s o m y of t h e t e r m i n a l p o r t i o n of 14 a n d deficiency of t h e t e l o m e r e of 21 (Pfeiffer et al., 1973). W e r e p o r t here a 3-year-old girl w i t h t r i s o m y of t h e s h o r t arms, centromere a n d a small p o r t i o n of t h e p r o x i m a l long arms of 14 whose m o t h e r a p p e a r s to h a v e t h e b a l a n c e d reciprocal t r a n s l o e a t i o n involving chromosome 16. ease Report The propositus (Figs. 1 and 2) was age 3 when she presented for examination because of developmental retardation. Her past history revealed her to have been the first born of apparently normal unrelated parents then age 26 (mother) and 24 (father). The prenatal course was complicated by premature rupture of the membranes at 36 weeks gestation requiring delivery by C section. The infant's birth weight was 1970 g and head circumference (IIC) 31.5 em and the neonatal course was complicated by the discovery of sagittal suture eraniostenosis. The infant's eraniostenosis required two neurosurgical procedures at 2~/2 and at 10 months of age. A third procedure to correct a CSF leak was performed at 1 year of age. * Operated by the University of Chicago for the U.S. Energy Research and Development Administration. This study was supported by the South Carolina Department of Mental Health.

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Figs. 1 and 2. The propositus Examination at the time of presentation revealed a caucasion female toddler of 3 years of age who showed developmental levels on the Coston-Chapman Developmental Scale (Coston and Chapman, 1974) as follows: gross motor function - - 2 years, sensory motor - 18 months, sociocmotional s k i l l s - 2½--3 years, language development - - 18 months. A physical examination revealed: height 92 cm, weight 13.5 kg, HC 48.5 em (all at the 50th percentile for chronological age). The child had seaphaloeephaly with mild frontal bossing and a palpable ridge along the sagittal suture. There was mild hypertelorism and a very mild saddling of the bridge of the nose. The upper central incisors were very small and pointed. There was a rough hypopigmented area approximately 2 × 3 em on the skin of the back in the midline at about T10 level. No abnormalities of eyes, ears, neck, hands, and genitalia were noted. There were no apparent, museuloskeletal abnormalities of the trunk or extremities. Cytogenetics Chromosome analysis of the propositus a n d her m o t h e r was performed on peripheral blood lymphocytes. A total of 50 metaphases were analyzed on each individual. C o n v e n t i o n a l Giemsa staining, G i e m s a - b a n d i n g (Seabright, 1971), Q - b a n d i n g (Caspersson et al., 1970), a n d C-banding (Sumner et al., 1971) were utilized. Metaphases e x a m i n e d from the child consistently h a d a very small m a r k e r chromosome (T1) in a d d i t i o n to a full n o r m a l female complement. Figure 3B is a partial k a r y o t y p e of the child which shows the T1 m a r k e r chromosome. The T1 chromosome, whose c o m p o n e n t parts we were u n a b l e to identify precisely using G-banding, is a b o u t one-third the size of a G-group chromosome. The m o t h e r ' s G - b a n d e d k a r y o t y p e showed a n u m b e r 14 a n d a n u m b e r 16 chromosome to be missing (Fig. 3A). There were present, however, the T1 m a r k e r chromosome a n d a large s u b m e t a e e n t r i e chromosome (T2) a b o u t the size of a B-group chromosome. F u r t h e r analysis revealed t h a t the short, arms a n d proximal

Tertiary Trisomy, 47,XX,+ 14q--

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Fig. 3. (A) G-banded karyotype of the mother. (B) G-banded partial karyotype of the propositus showing the D and E groups and the 14q-- chromosome (T1). (C) C-banded partial karyotype of the mother showing T1, T2, and the D and E groups. T2 exhibits the large C band typical of chromosome 16; T1 shows C-banding similar to that of chromosome 14 and dissimilar to that of 15. (D) Q-banded partial karyotype of the mother showing T1, T2 and the D and E groups p a r t of the long arms of T2 were the short arms and most of the long arms of a 16 (Figs. 3C and ])) and t h a t the distal portion of the long arms was composed of most of the long arms of chromosome 14. I t appears t h a t a break occurred in b a n d 16q2¢ near the terminus of the long arms, t h a t chromosome 14 was broken in band 1 4 q l l near the heterochromatic band 14q12, and t h a t the chromosom e segments diste~l to the breaks were interchanged, resulting in a balanced reciprocal translocation: 46,XX,t(14; 16) (14pter ~ 1 4 q l l :: 16q24 ~ 1 6 q t e r ; 16pter -~16q24 :: 1 4 q l l ~14qter). Marker chromosome T1 is composed of the short arms, centromere, and the proximal part of the long arms (including most of band ql 1) of chromosome 14 and the terminal portion of the long arms of chromosome 16.

Discussion The addition of large parts of chromosome 14 to the full k a r y o t y p e has significant effect on the phenotype. Full trisomy fetuses are either aborted or die

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shortly after birth (Murken et al., 1970; Kajii et al., 1972). I n eases where more t h a n one-half of the long arm is trisomic the effect is also severe, b u t not necessarily lethal (Allderdiee et al., 1971; Short et al., 1972; Pfeiffer et al., 1973). I f these children survive t h e y are moderately to severely mentally and physically retarded. The case presented here and t h a t of Fryns et al. (1974) seem to be cases of trisomy of less t h a n one-third of the long arm of chromosome 14. I t is interesting t h a t neither of these children is severely retarded and t h a t both have fairly well-developed soeio-emotional skills. Perhaps the most significant difference between these two cases is the craniostenosis found in our patient. Since the T1 chromosome was so small and showed no discernible banding pattern, banding techniques were not particularly helpful in elucidating the nature of the chromosomal abnormality in the propositus because t h e y revealed that, with the exception of T1, the rest of the chromosome complement was normal. Only after the parents' chromosomes were examined was it discovered t h a t the mother's k a r y o t y p e represents an example of balanced reciprocal translocation which has produced a condition of tertiary trisomy in the child. We presume t h a t the trisomy in this child arose t h r o u g h nondisjunetion during metaphase I in maternal gametogenesis. Additional studies of this family and comparisons with other patients with trisomy 1 4 q - - are being planned.

References Allderdice, P. W., Miller, O. J., Miller, D. A., Breg, W. R., Gendel, E., Zelson, C. : Familial translocation involving chromosomes 6, 14, and 20, identified by quinaerine fluorescence. Humangenetik 13, 205--209 (1971) Caspersson, T., Zech, C., Johansson, C., Modest, E. J. : Identification of human chromosomes by DNA-binding fluorescent agents. Chromosoma (Berl.) 30, 215--227 (1970) Coston, G. N., Chapman, S. K.: Coston-Chapman developmental scale. Columbia, South Carolina: University of South Carolina Press 1974 Fryns, J. P., Cassiman, J. J., van den Berghe, It. : Tertiary partial trisomy 47, XX,4-14q-. Humangenetik 24, 71--77 (1974) Laurent, C., Dutrillaux, B., Biemond, M. Cl., Genoud, J., Bethenod, M.: Translocation t(14q--;21q+) chez le pere. Trisomie 14 et monosomie 21 partielles ehez la fille. Ann. G6n@t. 16, 281--284 (1973) Murken, J. D., Bauehinger, M., Palitzsch, D., Pfeifer, H., Sushke, J., Haendle, H. : Trisomie D2 bei einem 2,5j~hrigen M~dchen (47,XX,14÷). Humangenetik 10, 254--268 (1970) Pfeiffer, 1~. A., Buttinghavs, K., Struk, H. : Partial trisomy 14 translocation t(14q--;21qZr). ttumangenetik 20, 187--189 (1973) ~eiss, J. A., Wyandt, H. E., Magenis, R. E., Lovrien, E. W., Hecht, F.: Mosaicism with translocation: autoradiographic and fluorescent studies of an inherited reciprocal translocation t(2q+;14q--). J. reed. Genet. 9, 2 8 0 286 (1972) Seabright, M. : A rapid banding technique for human chromosomes. Lancet 1971 II, 971--972 Short, E. M., Solitare, G. B., Breg, W. I~.: A case of partial 14 trisomy 47,XY,(14q--)-~and transloeation t(9p~- ; 14q--) in mother and brother. J. reed. Genet. 9, 367 373 (1972) Sumner, A. T., Evans, H. J., Buckland, R. A.: New technique for distinguishing between human chromosomes. Nature (Lond.) New Biol. 232, 31--32 (1971) Dr. S. Robert Young Chief, Genetics Laboratory William S. Hall Psychiatric Institute P.O. Box 119 Columbia, South Carolina 29202 USA