EuropeanJournal of
Eur. J. Pediatr. 130, 189--192(1979)
Pediatrics 9 by Springer-Verlag 1979
Case Reports
18q- Syndrome in Mother and Daughter J. P. F r y n s , N. Logghe*, M. van Eygen*, a n d H. van den Berghe Division of Human Genetics, Department of Human Biology, Minderbroedersstraat, 12, B-3000 Leuven, Belgium
Abstract. The 1 8 q - s y n d r o m e is d e s c r i b e d in a m o t h e r a n d her d a u g h t e r . In b o t h o f t h e m an identical, a p p a r e n t l y b a l a n c e d 1 8 q - / 1 4 p + t r a n s l o c a t i o n was f o u n d ( K a r y o t y p e : 4 6 , X X , t ( 1 4 ; 1 8 ) ( p l l ; q 2 1 ) ) , suggesting that c h r o m o s o m a l m a t e r i a l was lost in the process o f t r a n s l o c a t i o n . The segment deleted a n d r e s p o n s i b l e for the 1 8 q - p h e n o t y p e m u s t be l o c a t e d in o r n e a r b a n d 18q21, in which the b r e a k is a s s u m e d to have occurred.
Key words: C h r o m o s o m e deletion - C h r o m o s o m e s 16--18 - F a m i l i a l a n d genetic m e n t a l r e t a r d a t i o n - F a m i l i a l a n d genetic t r a n s l o c a t i o n .
P a r t i a l m o n o s o m y o f the long a r m o f c h r o m o s o m e n u m b e r 18 was recognized as a clinical entity b y Lejeune et al. (1966). M o r e t h a n 50 cases were described d u r i n g the last 10 years (for review D e G r o u c h y a n d T u r l e a u , 1977). Since the i n t r o d u c t i o n o f different b a n d i n g - t e c h n i q u e s , familial occurrence o f this c h r o m o s o m a l d e l e t i o n s y n d r o m e in a m o t h e r a n d one o r m o r e children has been r e p o r t e d b y S u b r t a n d P o k o r n y (1970) a n d b y Sulzer a n d Zierler (1976).
Case Report C.D. was the first child of moderately mentally retarded parents. At birth the father was aged 39 years and the mother 49 years. Besides mental retardation, the mother presented slight craniofacial dysmorphism with a sloping forehead and relative enophthalmia (Fig. 1). She was visually handicapped because of tapetoretinal degeneration. The family history was negative with regard to other cases of mental retardation, miscarriages and congenital malformations. The only sister of the mother had six normal children. Clinical examination of the father was normal. The etiology of his moderate mental retardation is unknown. Pregnancy and delivery at 39 weeks were normal. Birth weight was 2600g. No perinatal problems were noted. Severe psychomotor retardation and failure to thrive with recurrent upper respiratory tract infections soon became obvious. At the age of 6 years she was admitted to the paediatric hospital for general evaluation. The child was profoundly mentally retarded, severely hypotonic, and could not sit without support. *
Paediatricians--B-8800 Roeselare, Belgium
0340-6199/79/0130/0189/$01.00
190
J. R Fryns et al.
Fig. 1. The mother Fig. 2. The propositus Continuous choreoathetotic movements were present, especially of the arms. Her weight was 13kg (P2,5: 16.4kg), her length 104cm (P2,5: 106.8cm) and her head circumference 46cm (P 2,5:46.8 cm). Several craniofacial stigmata (Fig. 2) were found with microcephaly, a small sloping forehead, deeply set eyes, a small upturned nose, a short everted upper lip and triangular mouth. Her poorly lobulated ears were in normal position. Her fingers and toes were long and slender. Genua valga and bilateral halluces valgi were the only other associated skeletal anomalies. Biochemical and metabolic screening was negative. Immunoglobulins were normal.
t3
14
.
15
.
.
.
16
17
~---...._____~
Fig. 3a. D- and E-group chromosomes of the propositus (G-bands--three cells)
18
18q- Syndrome
191
Fig. 3b. D- and E-group chromosomes of the mother (one cell after R-banding and one cell after Q-banding)
An X-ray skeletal survey and intravenous pyelogram were without pecularities. The electroencephalograph was diffusely disturbed without lateralisation. Computerized axial tomography showed extensive porencephaly of the right frontal lobe.
Cytogenetic Studies Forty-five cells from two different lymphocyte cultures were examined. With the exception of one cell in which there was loss of a B- and a C-group chromosome, 46 chromosomes were always found. Banding-techniques (G-, Q-, C- and R-banding) showed a seemingly balanced translocation between the short arm of chromosome number 14 and the long arm of chromosome number 18. The breakpoints presumably were 14pll and 18q21. Karyotype: 46,XX, t(14;18)(pl 1;q21) (Fig. 3). The same 18q-/14p+ translocation was found in the karyotype of the mother. The karyotype of the father was normal. No other members of the mother's family could be investigated.
Discussion The p r e s e n t family is the t h i r d e x a m p l e o f familial occurrence o f the 1 8 q s y n d r o m e in a m o t h e r a n d one o r m o r e children which has been described since the i n t r o d u c t i o n of b a n d i n g techniques. S u b r t a n d P o k o r n y (1970) r e p o r t e d a p a r t i a l l o n g - a r m deletion o f c h r o m o s o m e 18 in a m o t h e r a n d f o u r d a u g h t e r s , a n d Sulzer a n d Zierler (1970) d e s c r i b e d the s a m e k a r y o t y p i c a n o m a l y in a m o t h e r a n d d a u g h t e r , In the p r e s e n t r e p o r t , the k a r y o t y p e s o f m o t h e r a n d child are identical a n d are c h a r a c t e r i z e d by a structural r e a r r a n g e m e n t between the short a r m o f one c h r o m o s o m e 14 a n d the long a r m o f one c h r o m o s o m e 18. K a r y o t y p e : 46,XX, t( 14; 18)(p 11 ;q21). W i t h the techniques used a loss o f c h r o m o s o m a l m a t e r i a l c o u l d n o t be d e m o n s t r a t e d . It is h o w e v e r likely t h a t some m a t e r i a l o f the 18q is missing, since b o t h p a t i e n t s have an a b n o r m a l p h e n o t y p e indistinguishable f r o m t h a t o f the 1 8 q - s y n d r o m e . Such seemingly b a l a n c e d t r a n s l o c a t i o n s are also f o u n d in patients with p r o f o u n d m e n t a l r e t a r d a t i o n at a frequency which m a y be as high as
J. P. Fryns et al.
192 Table 1. Comparison of the most important symptoms in the 18qsyndrome with the stigmata found in the present cases
Mental deficiency Growth failure Microcephaly Midface dysplasia Antihelix-antitragus hypertrophy Carp-shaped mouth Tapering fingers Dimples Ophthalmologic anomalies Excess whorls
Mother
Daughter
+ + + -
+ + + + + + + -
8 times t h a t o b s e r v e d in systematic n e w b o r n - s t u d i e s ( F u n d e r b u r k et al., 1977; J a c o b s et al., 1978). H e r e too, one o f the plausible e x p l a n a t i o n s is t h a t a deletion, u n d e t e c t a b l e b y the p r e s e n t techniques, m a y be present a n d m a y be responsible for the p h e n o t y p i c m a n i f e s t a t i o n s . If a deletion occurred in the present family, it m u s t have been relatively small, a n d in t h a t case the segment deleted a n d r e s p o n s i b l e for the s y m p t o m s o f the 1 8 q - s y n d r o m e m u s t be l o c a t e d in o r near b a n d 18q21 in which the b r e a k is a s s u m e d to have occurred. As in o t h e r c h r o m o s o m a l a n o m a l i e s , the intensity o f the features o f the 1 8 q - s y n d r o m e m a y v a r y s o m e w h a t . This is a l r e a d y o b v i o u s f r o m the cases r e p o r t e d in the literature, a n d is also i l l u s t r a t e d in the p r e s e n t family, in which the child is m o r e severely affected t h a n the m o t h e r . A t the age o f 7 years the child was severely h y p o t o n i c with gross n e u r o l o g i c a l i m p a i r m e n t a n d c h o r e o a t h e t o t i c m o v e m e n t s . H e r craniofacial stigm a t a were very characteristic with m o d e r a t e m i c r o c e p h a l y , slight r e t r a c t i o n o f the mid-face with relative e n o p h t h a l m i a , a small u p t u r n e d nose, a s h o r t p h i l t r u m a n d an everted u p p e r lip. The long, slender fingers a n d toes are equally typical o f this c h r o m o s o m a l d e l e t i o n s y n d r o m e (Table 1). The t a p e t o r e t i n a l d e g e n e r a t i o n f o u n d in the m o t h e r has n o t been p r e v i o u s l y r e p o r t e d , b u t c o u l d be a late m a n i f e s t a t i o n o f this s y n d r o m e .
References Funderburk, J. J., Sparkes, R. S., Guthrie, D., Westlake, J.: Mental retardation associated with balanced chromosome rearrangements. Birth Defects: Original Article Series, XIII, 3 C, 232 (1977) Grouchy, J. de, Turleau, C.: Atlas des maladies chromosomiques. Expansion Scientifique Frangaise, Paris, 210--215 (1977) Jacobs, P.A., Matsuura, J.S., Mayer, M., Newlands, I.: A cytogenic survey of an institution for the mentally retarded. I. Chromosome abnormalities. Clin. Genet. 13, 37--60 (1978) Lejeune, J., Berger, R., Lafourcade, J., Rethor6, M.O.: La d616tion du bras long du chromosome 18. Individualisation d'un nouvel 6tat morbide. Ann. Genet. (Paris) 9, 32--38 (1966) Subrt, I., Pokorny, J.: Familial occurrence of 18q-. Humangenetik 10, 181--187 (1970) Sulzer, M., Zierler, H.: 18q- Deletion bei Mutter und Tochter. Wien. Klin. Wochenschr. 88, 571--575 (1976) Received September 17, 1978
Eur. J. Pediatr. 130, 189--192(1979)
Pediatrics 9 by Springer-Verlag 1979
Case Reports
18q- Syndrome in Mother and Daughter J. P. F r y n s , N. Logghe*, M. van Eygen*, a n d H. van den Berghe Division of Human Genetics, Department of Human Biology, Minderbroedersstraat, 12, B-3000 Leuven, Belgium
Abstract. The 1 8 q - s y n d r o m e is d e s c r i b e d in a m o t h e r a n d her d a u g h t e r . In b o t h o f t h e m an identical, a p p a r e n t l y b a l a n c e d 1 8 q - / 1 4 p + t r a n s l o c a t i o n was f o u n d ( K a r y o t y p e : 4 6 , X X , t ( 1 4 ; 1 8 ) ( p l l ; q 2 1 ) ) , suggesting that c h r o m o s o m a l m a t e r i a l was lost in the process o f t r a n s l o c a t i o n . The segment deleted a n d r e s p o n s i b l e for the 1 8 q - p h e n o t y p e m u s t be l o c a t e d in o r n e a r b a n d 18q21, in which the b r e a k is a s s u m e d to have occurred.
Key words: C h r o m o s o m e deletion - C h r o m o s o m e s 16--18 - F a m i l i a l a n d genetic m e n t a l r e t a r d a t i o n - F a m i l i a l a n d genetic t r a n s l o c a t i o n .
P a r t i a l m o n o s o m y o f the long a r m o f c h r o m o s o m e n u m b e r 18 was recognized as a clinical entity b y Lejeune et al. (1966). M o r e t h a n 50 cases were described d u r i n g the last 10 years (for review D e G r o u c h y a n d T u r l e a u , 1977). Since the i n t r o d u c t i o n o f different b a n d i n g - t e c h n i q u e s , familial occurrence o f this c h r o m o s o m a l d e l e t i o n s y n d r o m e in a m o t h e r a n d one o r m o r e children has been r e p o r t e d b y S u b r t a n d P o k o r n y (1970) a n d b y Sulzer a n d Zierler (1976).
Case Report C.D. was the first child of moderately mentally retarded parents. At birth the father was aged 39 years and the mother 49 years. Besides mental retardation, the mother presented slight craniofacial dysmorphism with a sloping forehead and relative enophthalmia (Fig. 1). She was visually handicapped because of tapetoretinal degeneration. The family history was negative with regard to other cases of mental retardation, miscarriages and congenital malformations. The only sister of the mother had six normal children. Clinical examination of the father was normal. The etiology of his moderate mental retardation is unknown. Pregnancy and delivery at 39 weeks were normal. Birth weight was 2600g. No perinatal problems were noted. Severe psychomotor retardation and failure to thrive with recurrent upper respiratory tract infections soon became obvious. At the age of 6 years she was admitted to the paediatric hospital for general evaluation. The child was profoundly mentally retarded, severely hypotonic, and could not sit without support. *
Paediatricians--B-8800 Roeselare, Belgium
0340-6199/79/0130/0189/$01.00
190
J. R Fryns et al.
Fig. 1. The mother Fig. 2. The propositus Continuous choreoathetotic movements were present, especially of the arms. Her weight was 13kg (P2,5: 16.4kg), her length 104cm (P2,5: 106.8cm) and her head circumference 46cm (P 2,5:46.8 cm). Several craniofacial stigmata (Fig. 2) were found with microcephaly, a small sloping forehead, deeply set eyes, a small upturned nose, a short everted upper lip and triangular mouth. Her poorly lobulated ears were in normal position. Her fingers and toes were long and slender. Genua valga and bilateral halluces valgi were the only other associated skeletal anomalies. Biochemical and metabolic screening was negative. Immunoglobulins were normal.
t3
14
.
15
.
.
.
16
17
~---...._____~
Fig. 3a. D- and E-group chromosomes of the propositus (G-bands--three cells)
18
18q- Syndrome
191
Fig. 3b. D- and E-group chromosomes of the mother (one cell after R-banding and one cell after Q-banding)
An X-ray skeletal survey and intravenous pyelogram were without pecularities. The electroencephalograph was diffusely disturbed without lateralisation. Computerized axial tomography showed extensive porencephaly of the right frontal lobe.
Cytogenetic Studies Forty-five cells from two different lymphocyte cultures were examined. With the exception of one cell in which there was loss of a B- and a C-group chromosome, 46 chromosomes were always found. Banding-techniques (G-, Q-, C- and R-banding) showed a seemingly balanced translocation between the short arm of chromosome number 14 and the long arm of chromosome number 18. The breakpoints presumably were 14pll and 18q21. Karyotype: 46,XX, t(14;18)(pl 1;q21) (Fig. 3). The same 18q-/14p+ translocation was found in the karyotype of the mother. The karyotype of the father was normal. No other members of the mother's family could be investigated.
Discussion The p r e s e n t family is the t h i r d e x a m p l e o f familial occurrence o f the 1 8 q s y n d r o m e in a m o t h e r a n d one o r m o r e children which has been described since the i n t r o d u c t i o n of b a n d i n g techniques. S u b r t a n d P o k o r n y (1970) r e p o r t e d a p a r t i a l l o n g - a r m deletion o f c h r o m o s o m e 18 in a m o t h e r a n d f o u r d a u g h t e r s , a n d Sulzer a n d Zierler (1970) d e s c r i b e d the s a m e k a r y o t y p i c a n o m a l y in a m o t h e r a n d d a u g h t e r , In the p r e s e n t r e p o r t , the k a r y o t y p e s o f m o t h e r a n d child are identical a n d are c h a r a c t e r i z e d by a structural r e a r r a n g e m e n t between the short a r m o f one c h r o m o s o m e 14 a n d the long a r m o f one c h r o m o s o m e 18. K a r y o t y p e : 46,XX, t( 14; 18)(p 11 ;q21). W i t h the techniques used a loss o f c h r o m o s o m a l m a t e r i a l c o u l d n o t be d e m o n s t r a t e d . It is h o w e v e r likely t h a t some m a t e r i a l o f the 18q is missing, since b o t h p a t i e n t s have an a b n o r m a l p h e n o t y p e indistinguishable f r o m t h a t o f the 1 8 q - s y n d r o m e . Such seemingly b a l a n c e d t r a n s l o c a t i o n s are also f o u n d in patients with p r o f o u n d m e n t a l r e t a r d a t i o n at a frequency which m a y be as high as
J. P. Fryns et al.
192 Table 1. Comparison of the most important symptoms in the 18qsyndrome with the stigmata found in the present cases
Mental deficiency Growth failure Microcephaly Midface dysplasia Antihelix-antitragus hypertrophy Carp-shaped mouth Tapering fingers Dimples Ophthalmologic anomalies Excess whorls
Mother
Daughter
+ + + -
+ + + + + + + -
8 times t h a t o b s e r v e d in systematic n e w b o r n - s t u d i e s ( F u n d e r b u r k et al., 1977; J a c o b s et al., 1978). H e r e too, one o f the plausible e x p l a n a t i o n s is t h a t a deletion, u n d e t e c t a b l e b y the p r e s e n t techniques, m a y be present a n d m a y be responsible for the p h e n o t y p i c m a n i f e s t a t i o n s . If a deletion occurred in the present family, it m u s t have been relatively small, a n d in t h a t case the segment deleted a n d r e s p o n s i b l e for the s y m p t o m s o f the 1 8 q - s y n d r o m e m u s t be l o c a t e d in o r near b a n d 18q21 in which the b r e a k is a s s u m e d to have occurred. As in o t h e r c h r o m o s o m a l a n o m a l i e s , the intensity o f the features o f the 1 8 q - s y n d r o m e m a y v a r y s o m e w h a t . This is a l r e a d y o b v i o u s f r o m the cases r e p o r t e d in the literature, a n d is also i l l u s t r a t e d in the p r e s e n t family, in which the child is m o r e severely affected t h a n the m o t h e r . A t the age o f 7 years the child was severely h y p o t o n i c with gross n e u r o l o g i c a l i m p a i r m e n t a n d c h o r e o a t h e t o t i c m o v e m e n t s . H e r craniofacial stigm a t a were very characteristic with m o d e r a t e m i c r o c e p h a l y , slight r e t r a c t i o n o f the mid-face with relative e n o p h t h a l m i a , a small u p t u r n e d nose, a s h o r t p h i l t r u m a n d an everted u p p e r lip. The long, slender fingers a n d toes are equally typical o f this c h r o m o s o m a l d e l e t i o n s y n d r o m e (Table 1). The t a p e t o r e t i n a l d e g e n e r a t i o n f o u n d in the m o t h e r has n o t been p r e v i o u s l y r e p o r t e d , b u t c o u l d be a late m a n i f e s t a t i o n o f this s y n d r o m e .
References Funderburk, J. J., Sparkes, R. S., Guthrie, D., Westlake, J.: Mental retardation associated with balanced chromosome rearrangements. Birth Defects: Original Article Series, XIII, 3 C, 232 (1977) Grouchy, J. de, Turleau, C.: Atlas des maladies chromosomiques. Expansion Scientifique Frangaise, Paris, 210--215 (1977) Jacobs, P.A., Matsuura, J.S., Mayer, M., Newlands, I.: A cytogenic survey of an institution for the mentally retarded. I. Chromosome abnormalities. Clin. Genet. 13, 37--60 (1978) Lejeune, J., Berger, R., Lafourcade, J., Rethor6, M.O.: La d616tion du bras long du chromosome 18. Individualisation d'un nouvel 6tat morbide. Ann. Genet. (Paris) 9, 32--38 (1966) Subrt, I., Pokorny, J.: Familial occurrence of 18q-. Humangenetik 10, 181--187 (1970) Sulzer, M., Zierler, H.: 18q- Deletion bei Mutter und Tochter. Wien. Klin. Wochenschr. 88, 571--575 (1976) Received September 17, 1978
