Hum. Genet. 46, 243--247 (1979) © by Springer-Verlag 1979
Partial Trisomy 14q I. Lopez Pajares 1*, A. Delicado 1, P. V. Cobos 1, G. Lledo 2, and A. Peralta 2 Departamento de Laboratorio, Secci6n de Gen6tica, Ciudad Sanitaria de la Seguridad Social "La Paz," Madrid, Spain 2Cifnica Infannl "La Paz," Madrid, Spain
Summary. A dysmorphic female b o r n with partial trisomy of the proximal segment of the long a r m of c h r o m o s o m e 14 had 47 chromosomes. The extra one was acrocentric, smaller than the D group, and bigger than the Gc h r o m o s o m e group. By G T G banding it was identified as a deleted c h r o m o some 14, the karyotype being 47,XX,+del 14(q24). C h r o m o s o m e analysis o f the parents was normal.
Introduction Full trisomy 14 has been f o u n d in spontaneous abortions (Kajii et al., 1972). In live-born infants with mosaicism, it is extremely rare (Rethor6 et al., 1975). Partial trisomy 14, however, has been reported on a few occasions. Several cases trisomic for the short arm, the centromere region, and a variable part of the long arm o f c h r o m o s o m e 14 have been described (Allderdice et al., 1971; Reiss et al., 1972; Short et al., 1972; Laurent et al., 1973; Muldal et al., 1973; Fryns et al., 1974; Raoul et al., 1975; Turleau et al., 1975; Pena et al., 1976; Yeatman et al., 1976; Y o u n g et al., 1976; C o c o et al., 1977). Trisomy of the most distal part o f the long arm has been described (Pfeiffer et al., 1973; Fryns et al., 1977).
Case Report S.R. was born July 24, 1977 as the sixth child of healthy, unrelated parents. At birth, the mother was 41 years of age and the father was 42. The family history included two miscarriages and a dead fetus. Weight at birth (after 41 weeks) was 4080 g, length was 56 cm, and head circumference was 39.5 cm. The infant had cranial dysmorphy with hypertelorism, slightly mongoloid eye slits, a high-arched palate, a broad base of the nose, one umbilical artery, and low-set ears. The infant was moderately hypotonic. Cardiac examination revealed a systolic murmur. X-ray examination revealed a trigonocephalic skull and urography showed a descending left kidney with an incurvate ureter. *
To whom offprint requests should be sent
0340-6717/79/0046/0243/$01.00
244
I. Lopez Pajares et al.
Fig. 1. a Face of the patient. Note the macrocephaly and mongoloid position of eyes, and low-set ears. b The patient at the age of 2 months
Cytogenetic Investigations Chromosome analysis of the propositus was performed on peripheral blood lymphocytes. A total of 50 cells were examined with G- and Q-banding. In each cell there were 47 chromosomes. The extra chromosome was acrocentric, smaller than the D-chromosome group, and larger than the G-chromosome group, with visible satellites. After studies with different banding techniques (Q-banding, and G-banding) it was possible to determine that the extra chromosome was a 14 with a deletion in q24 (Figs. 2 and 3). Thus this patient had a partial trisomy of the short-arm centromere region and proximal part of the long arm of chromosome 14. The karyotype was 47,XX,+del 14(q24). Chromosome analysis of the parents was normal.
Discussion Full trisomy 14 seems to be highly lethal. There are no reported individuals who undoubtedly are trisomic for all of No. 14. Murken et al. (1970) reported one case with seven D-group chromosomes; three of which had D N A replication compatible with No. 14, but these have not been identified with banding techniques. Rethor6 et al. (1975) reported one case with full trisomy 14 and mosaicism.
Partial Trisomy 14q
Fig. 2.
245
D-group chromosomes from the proposita
I
2 1
1
2 3
1
1
1
1
2 3
3 2
1
2 3 1 2
2
3
2 4
1
3
2
Fig. 3. Schematic representation of a normal chromosome 14 and one with deletion of the long arm
246
I. Lopez Pajares et al.
P a r t i a l trisomies are m o r e likely to live for s o m e time, a n d the severity o f the c o n d i t i o n a p p a r e n t l y d e p e n d s o n which segment o f the long a r m is trisomic. The cases e x a m i n e d b y F r y n s et al. (1974), Y o u n g et al. (1976), a n d T u r l e a u et al. (I 975), were t r i s o m i c for a small p r o x i m a l p a r t o f the long a r m o f 14 a n d s h o w e d m i n o r m a l f o r m a t i o n s a n d m i l d m e n t a l deficiency. H o w e v e r , in the cases o f A l l d e r d i c e et al. (1971), Reiss et al. (1972), S h o r t et al. (1972), L a u r e n t et al. (1973), M u l d a l et al. (1973), a n d R a o u l et al. (1975) at least h a l f or m o r e o f the long a r m o f No. 14 was trisomic. These cases s h o w e d m a j o r m a l f o r m a t i o n s a n d grave m e n t a l deficiency. A review o f the cases with t r i s o m y o f the s h o r t a r m , c e n t r o m e r e region, a n d p r o x i m a l s e g m e n t o f the l o n g a r m o f c h r o m o s o m e 14 revealed a p h e n o t y p e with retardation of physical growth and mental development, microphthalmus, cardiac a n d l i m b a n o m a l i e s , low-set ears, m i c r o c e p h a l y , high a r c h e d o r cleft p a l a t e , a n d a p r o m i n e n t nose. O u r p a t i e n t s h o w e d m a c r o s o m i a a n d m a c r o c e p h a l y . T h e fact t h a t m o s t r e p o r t e d cases were also t r i s o m i c o r m o n o s o m i c for o t h e r c h r o m o s o m e segments p r o b a b l y a c c o u n t s for the o b s e r v e d p h e n o t y p i c variation. In all cases the m o t h e r or the f a t h e r c a r r i e d a b a l a n c e d reciprocal t r a n s l o c a t i o n . O n l y in the cases r e p o r t e d b y M u l d a l et al. (1973) a n d in o u r case was c h r o m o s o m e analysis o f the p a r e n t s n o r m a l .
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 quinacrine fluorescence. Humangenetik 13, 205--209 (1971) Coco, R., Penchaszadeh, V. B.: Partial trisomy 14q and familial translocation (2;14)(q12;q13). Ann. Genet. (Paris) 20, 41--44 (1977) Fryns, J. P.,Cassiman, J. J., van den Berghe,H.: Tertiary partial trisomy 47,XX,+ 14q-. Humangenetik 24, 71--77 (1974) Fryns, J. P., van Eygen, M., Tanghe, W., van den Berghe, H.: Partial trisomy 14q due to familial t(14q-;1 lq+) translocation. Hum. Genet. 37, 105--110 (1977) Kajii, T., Ohama, K., Ferrier, A.: Trisomy 14 in spontaneous abortus. Humangenetik 15, 265--267 (1972) Laurent, C., Dutrillaux, B., Biemond, M. C1., Genoud, J., Bethenod, M.: Translocation t(14q-; 21q+) chez le p~re, trisomie 14 et monosomie 21 partielles chez la fille. Ann. Genet. (Paris) 16, 281 (1973) Muldal, S., Enoch, B. A., Ahmed, A., Harris, R.: Partial trisomy 14q and pseudoxanthoma elasticum. Clin. Genet. 4, 480 (1973) Pena, D. J. S., Ray, M., McAlpine, P. J., Ducasse, C., Briggs, J., Hamerton, J.: Tertiary trisomy 14: Is there a syndrome? Birth Defects: Orig. Art. Ser., Vol. XII, 5, 113--118 (1976) Pfeiffer, R. A., Buttinghaus, K., Struck, H.: Partial trisomy 14, following a balanced reciprocal translocation t(14q-;21q+). Humangenetik 20, 187--189 (1973) Raoul, O., Rethor6, M. O., Dutrillaux, B., Michon, L., Lejeune, J.: Trisomie 14q partielle. I. Trisomie 14q partielle par translocation maternelle t(10;14)(p15.2;q22). Ann. Genet. (Paris) 18, 35 (1975) Reiss, 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. Med. Genet. 9, 280 (1972) Rethor6, M. O., Couturier, J., Carpentier, S., Ferrand, J., Lejeune, J.: Trisomie 14 en mosaique chez une enfant multimalforme6. Ann. Genet. (Paris) 18, 71--74 (1975) Short, E. M., Solitare, G. B., Brag, W. R.: A case of partial 14 trisomy 47,XY (19q-)+ and translocation t(9p+;14q-) in mother and brother. J. Med. Genet. 9, 367 (1972)
Partial Trisomy 14q
247
Turleau, C., de Grouchy, J., Bocquentin, F., Roubin, M., Chavin-Colin, F.: La trisomie 14q partielle. II. Trisomie 14q partielle par translocation maternelle t(12;14)(q24.4;q21). Ann. Genet. (Paris) 18, 41 (1975) Yeatman, G. W., Riccardi, V. M.: Partial trisomy 14:(+14q-). Birth Defects: Orig. Art. Ser., Vol. XII, 5, 119--124 (1976) Young, R. S., Donovan, D. M., Greer, H. A., Butch, K., Potter, D. C.: Tertiary trisomy, 47,XX,+14q+, resulting from maternal balanced translocation 46,XX,t(14;16)(q11;q24). Hum. Genet. 33, 331--334 (1976) Received December 22, 1977
Partial Trisomy 14q I. Lopez Pajares 1*, A. Delicado 1, P. V. Cobos 1, G. Lledo 2, and A. Peralta 2 Departamento de Laboratorio, Secci6n de Gen6tica, Ciudad Sanitaria de la Seguridad Social "La Paz," Madrid, Spain 2Cifnica Infannl "La Paz," Madrid, Spain
Summary. A dysmorphic female b o r n with partial trisomy of the proximal segment of the long a r m of c h r o m o s o m e 14 had 47 chromosomes. The extra one was acrocentric, smaller than the D group, and bigger than the Gc h r o m o s o m e group. By G T G banding it was identified as a deleted c h r o m o some 14, the karyotype being 47,XX,+del 14(q24). C h r o m o s o m e analysis o f the parents was normal.
Introduction Full trisomy 14 has been f o u n d in spontaneous abortions (Kajii et al., 1972). In live-born infants with mosaicism, it is extremely rare (Rethor6 et al., 1975). Partial trisomy 14, however, has been reported on a few occasions. Several cases trisomic for the short arm, the centromere region, and a variable part of the long arm o f c h r o m o s o m e 14 have been described (Allderdice et al., 1971; Reiss et al., 1972; Short et al., 1972; Laurent et al., 1973; Muldal et al., 1973; Fryns et al., 1974; Raoul et al., 1975; Turleau et al., 1975; Pena et al., 1976; Yeatman et al., 1976; Y o u n g et al., 1976; C o c o et al., 1977). Trisomy of the most distal part o f the long arm has been described (Pfeiffer et al., 1973; Fryns et al., 1977).
Case Report S.R. was born July 24, 1977 as the sixth child of healthy, unrelated parents. At birth, the mother was 41 years of age and the father was 42. The family history included two miscarriages and a dead fetus. Weight at birth (after 41 weeks) was 4080 g, length was 56 cm, and head circumference was 39.5 cm. The infant had cranial dysmorphy with hypertelorism, slightly mongoloid eye slits, a high-arched palate, a broad base of the nose, one umbilical artery, and low-set ears. The infant was moderately hypotonic. Cardiac examination revealed a systolic murmur. X-ray examination revealed a trigonocephalic skull and urography showed a descending left kidney with an incurvate ureter. *
To whom offprint requests should be sent
0340-6717/79/0046/0243/$01.00
244
I. Lopez Pajares et al.
Fig. 1. a Face of the patient. Note the macrocephaly and mongoloid position of eyes, and low-set ears. b The patient at the age of 2 months
Cytogenetic Investigations Chromosome analysis of the propositus was performed on peripheral blood lymphocytes. A total of 50 cells were examined with G- and Q-banding. In each cell there were 47 chromosomes. The extra chromosome was acrocentric, smaller than the D-chromosome group, and larger than the G-chromosome group, with visible satellites. After studies with different banding techniques (Q-banding, and G-banding) it was possible to determine that the extra chromosome was a 14 with a deletion in q24 (Figs. 2 and 3). Thus this patient had a partial trisomy of the short-arm centromere region and proximal part of the long arm of chromosome 14. The karyotype was 47,XX,+del 14(q24). Chromosome analysis of the parents was normal.
Discussion Full trisomy 14 seems to be highly lethal. There are no reported individuals who undoubtedly are trisomic for all of No. 14. Murken et al. (1970) reported one case with seven D-group chromosomes; three of which had D N A replication compatible with No. 14, but these have not been identified with banding techniques. Rethor6 et al. (1975) reported one case with full trisomy 14 and mosaicism.
Partial Trisomy 14q
Fig. 2.
245
D-group chromosomes from the proposita
I
2 1
1
2 3
1
1
1
1
2 3
3 2
1
2 3 1 2
2
3
2 4
1
3
2
Fig. 3. Schematic representation of a normal chromosome 14 and one with deletion of the long arm
246
I. Lopez Pajares et al.
P a r t i a l trisomies are m o r e likely to live for s o m e time, a n d the severity o f the c o n d i t i o n a p p a r e n t l y d e p e n d s o n which segment o f the long a r m is trisomic. The cases e x a m i n e d b y F r y n s et al. (1974), Y o u n g et al. (1976), a n d T u r l e a u et al. (I 975), were t r i s o m i c for a small p r o x i m a l p a r t o f the long a r m o f 14 a n d s h o w e d m i n o r m a l f o r m a t i o n s a n d m i l d m e n t a l deficiency. H o w e v e r , in the cases o f A l l d e r d i c e et al. (1971), Reiss et al. (1972), S h o r t et al. (1972), L a u r e n t et al. (1973), M u l d a l et al. (1973), a n d R a o u l et al. (1975) at least h a l f or m o r e o f the long a r m o f No. 14 was trisomic. These cases s h o w e d m a j o r m a l f o r m a t i o n s a n d grave m e n t a l deficiency. A review o f the cases with t r i s o m y o f the s h o r t a r m , c e n t r o m e r e region, a n d p r o x i m a l s e g m e n t o f the l o n g a r m o f c h r o m o s o m e 14 revealed a p h e n o t y p e with retardation of physical growth and mental development, microphthalmus, cardiac a n d l i m b a n o m a l i e s , low-set ears, m i c r o c e p h a l y , high a r c h e d o r cleft p a l a t e , a n d a p r o m i n e n t nose. O u r p a t i e n t s h o w e d m a c r o s o m i a a n d m a c r o c e p h a l y . T h e fact t h a t m o s t r e p o r t e d cases were also t r i s o m i c o r m o n o s o m i c for o t h e r c h r o m o s o m e segments p r o b a b l y a c c o u n t s for the o b s e r v e d p h e n o t y p i c variation. In all cases the m o t h e r or the f a t h e r c a r r i e d a b a l a n c e d reciprocal t r a n s l o c a t i o n . O n l y in the cases r e p o r t e d b y M u l d a l et al. (1973) a n d in o u r case was c h r o m o s o m e analysis o f the p a r e n t s n o r m a l .
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 quinacrine fluorescence. Humangenetik 13, 205--209 (1971) Coco, R., Penchaszadeh, V. B.: Partial trisomy 14q and familial translocation (2;14)(q12;q13). Ann. Genet. (Paris) 20, 41--44 (1977) Fryns, J. P.,Cassiman, J. J., van den Berghe,H.: Tertiary partial trisomy 47,XX,+ 14q-. Humangenetik 24, 71--77 (1974) Fryns, J. P., van Eygen, M., Tanghe, W., van den Berghe, H.: Partial trisomy 14q due to familial t(14q-;1 lq+) translocation. Hum. Genet. 37, 105--110 (1977) Kajii, T., Ohama, K., Ferrier, A.: Trisomy 14 in spontaneous abortus. Humangenetik 15, 265--267 (1972) Laurent, C., Dutrillaux, B., Biemond, M. C1., Genoud, J., Bethenod, M.: Translocation t(14q-; 21q+) chez le p~re, trisomie 14 et monosomie 21 partielles chez la fille. Ann. Genet. (Paris) 16, 281 (1973) Muldal, S., Enoch, B. A., Ahmed, A., Harris, R.: Partial trisomy 14q and pseudoxanthoma elasticum. Clin. Genet. 4, 480 (1973) Pena, D. J. S., Ray, M., McAlpine, P. J., Ducasse, C., Briggs, J., Hamerton, J.: Tertiary trisomy 14: Is there a syndrome? Birth Defects: Orig. Art. Ser., Vol. XII, 5, 113--118 (1976) Pfeiffer, R. A., Buttinghaus, K., Struck, H.: Partial trisomy 14, following a balanced reciprocal translocation t(14q-;21q+). Humangenetik 20, 187--189 (1973) Raoul, O., Rethor6, M. O., Dutrillaux, B., Michon, L., Lejeune, J.: Trisomie 14q partielle. I. Trisomie 14q partielle par translocation maternelle t(10;14)(p15.2;q22). Ann. Genet. (Paris) 18, 35 (1975) Reiss, 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. Med. Genet. 9, 280 (1972) Rethor6, M. O., Couturier, J., Carpentier, S., Ferrand, J., Lejeune, J.: Trisomie 14 en mosaique chez une enfant multimalforme6. Ann. Genet. (Paris) 18, 71--74 (1975) Short, E. M., Solitare, G. B., Brag, W. R.: A case of partial 14 trisomy 47,XY (19q-)+ and translocation t(9p+;14q-) in mother and brother. J. Med. Genet. 9, 367 (1972)
Partial Trisomy 14q
247
Turleau, C., de Grouchy, J., Bocquentin, F., Roubin, M., Chavin-Colin, F.: La trisomie 14q partielle. II. Trisomie 14q partielle par translocation maternelle t(12;14)(q24.4;q21). Ann. Genet. (Paris) 18, 41 (1975) Yeatman, G. W., Riccardi, V. M.: Partial trisomy 14:(+14q-). Birth Defects: Orig. Art. Ser., Vol. XII, 5, 119--124 (1976) Young, R. S., Donovan, D. M., Greer, H. A., Butch, K., Potter, D. C.: Tertiary trisomy, 47,XX,+14q+, resulting from maternal balanced translocation 46,XX,t(14;16)(q11;q24). Hum. Genet. 33, 331--334 (1976) Received December 22, 1977
