Hum. Genet. 39, 239--242 (1977) © by Springer-Verlag 1977
Pericentric Inversion and Partial Monosomy 4q Associated with Congenital Anomalies Franqoise Serville a n d A. Broustet Laboratoire de Cytog6n6tique du Centre de Transfusion, F-33035 Bordeaux, France
Summary. A
case of complex structural r e a r r a n g e m e n t of c h r o m o s o m e 4 identified by R - b a n d i n g as 4 6 , X X , d e l ( 4 ) , i n v ( 4 ) ( p t e r - 16:: q 2 4 - p 1 6 :: q 3 2 qter) is reported in a n i n f a n t with congenital anomalies a n d p s y c h o m o t o r retardation.
Case Report The proposita was the 2800 g female product of the first and only pregnancy of a 28-year-old mother and a 26-year-old father. The parents were unrelated, the family history was noncontributory, and the pregnancy was uneventful, but fetal movements were not perceived by the mother. Delivery occurred 13 days after term. There was a breech presentation. A caesarean section was done and an oligohydramnios, a short umbilical cord, and an 'abnormal placenta' were noted. The baby developed edema in the neonatal period and tube feedings were required during three months because of poor sucking. This was followed by failure to thrive, respiratory infections, paroxysmal cyanosis and tachycardia crisis, and psychomotor retardation. She was referred to us at 161/2months with height of 64.5 cm (-1 S.D.), weight of 5200 g (-4 S.D.), and head circumference of 43.5 cm (-2.5 S.D.).
Fig. 1. Appearance of the child
240
Fig.2. RHG-banded metaphase plate
F. Serville and A. Broustet
Pericentric Inversion and Partial Monosomy 4q
241
Clinical findings included (Fig. 1): round skull; large bregmatic fontanel; prominent forehead; effaced supraorbital ridges; height of the middle part of the face reduced comparatively to the upper and lower facial heights; bilateral epicanthus inversus; microphthalmia and ectopic pupils; anteverted and bulbous nose; broad upper lip without visible philtrum; down-turned corner of mouth; high-arched palate; low-set ears with prominent right fossa; cylindric trunk; narrow pelvis; anterior position of anus; car6 au lait spot on the right knee; and left single palmar crease. There was no cardiac murmur. A Gesell test put the developmental abilities of the patient at about the 10-week level. There was not serious sensory deficiency and the cry was normal. Bone age corresponded to 9--10months. IVP showed left renal and ureteral bifidity. An EEG was normal.
Cytogenetic Investigation L e u c o c y t e culture o f p e r i p h e r a l b l o o d b y s t a n d a r d m e t h o d s revealed 46 c h r o m o somes. T w e n t y - t w o cells were a n a l y s e d with the R H G - b a n d i n g technique (see G r o u c h y a n d T u r l e a u , 1977). One B c h r o m o s o m e was missing a n d there was a s u p e r n u m e r a r y m e t a c e n t r i c C identified as c h r o m o s o m e 4 (Figs. 2 a n d 3). The s t r u c t u r a l r e a r r a n g e m e n t c o u l d be explained b y three b r e a k p o i n t s (Fig. 4). The segment lying between b a n d s 4p16 a n d 4q24 was inverted a n d the segment lying between b a n d s 4q24 a n d 4q32 was deleted. Thus, the overall d e s i g n a t i o n o f the p r o b a n d ' s k a r y o t y p e was: 46,XX,del(4),inv(4)(pter~p16 : : q 2 4 - p 1 6 : : q 3 2 - q t e r ) . The c h r o m o s o m e c o m p l e m e n t o f b o t h p a r e n t s was n o r m a l .
Fig. 3. Chromosome pairs No. 4 from five different cells (RHG-banding)
6--
(--
Fig. 4. Possible location of break points
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F. Serville and A. Broustet
Comments T w o cases o f p a r t i a l m o n o s o m y 4q have been identified b y b a n d i n g techniques to date: one case b y G o l b u s et al. (1973) a n d the o t h e r b y V a n K e m p e n (1975). T h e clinical features include g r o w t h a n d m e n t a l r e t a r d a t i o n , s h o r t a n t e v e r t e d nose, p a l a t o s c h i s i s , m i c r o g n a t h i a , a n d s u p e r i o r l y p o i n t e d ears. In the two cases the s a m e segment 4 q 3 1 - q t e r is deleted. O u r p a t i e n t ' s k a r y o t y p e s h o w e d an interstitial deletion o f the segment lying b e t w e e n b a n d s 4q24 a n d 4q32. T h e r e f o r e it w o u l d be a p r e s u m p t i o n to c o m p a r e h e r p h e n o t y p e to the p r e v i o u s cases. Acknowledgements. We thank M.-J. Bourdeau and M. Gachet for their skilful laboratory help. Note Added in Proof
At 4 years, the proposita weighted 7000 g and was 79 cm tall; she died as a result of a respiratory infection and the autopsy examination (by N. Frenck) revealed lung edema with atelectasis or emphysema, hypertrophy of heart with patent foramen ovale and endocardial fibro-elastosis of the ventricles and the right atrium.
References Golbus, M. S., Conte, F. A., Daentl, D. L.: Deletion from the long arm of chromosome 4 (46,XX,4q-) associated with congenital anomalies. J. Med. Genet. 10, 83--85 (1973) Grouchy, J. de, Turleau, C.: Atlas des Maladies Chromosomiques. Paris: Expansion Scientifique 1977 Van Kempen, C.: A patient with congenital anomalies and a deletion of the long arm of chromosome 4 [46,XY, del(4)(q31)]. J. Med. Genet. 12, 204--207 (1975) Received June 1, 1977
Pericentric Inversion and Partial Monosomy 4q Associated with Congenital Anomalies Franqoise Serville a n d A. Broustet Laboratoire de Cytog6n6tique du Centre de Transfusion, F-33035 Bordeaux, France
Summary. A
case of complex structural r e a r r a n g e m e n t of c h r o m o s o m e 4 identified by R - b a n d i n g as 4 6 , X X , d e l ( 4 ) , i n v ( 4 ) ( p t e r - 16:: q 2 4 - p 1 6 :: q 3 2 qter) is reported in a n i n f a n t with congenital anomalies a n d p s y c h o m o t o r retardation.
Case Report The proposita was the 2800 g female product of the first and only pregnancy of a 28-year-old mother and a 26-year-old father. The parents were unrelated, the family history was noncontributory, and the pregnancy was uneventful, but fetal movements were not perceived by the mother. Delivery occurred 13 days after term. There was a breech presentation. A caesarean section was done and an oligohydramnios, a short umbilical cord, and an 'abnormal placenta' were noted. The baby developed edema in the neonatal period and tube feedings were required during three months because of poor sucking. This was followed by failure to thrive, respiratory infections, paroxysmal cyanosis and tachycardia crisis, and psychomotor retardation. She was referred to us at 161/2months with height of 64.5 cm (-1 S.D.), weight of 5200 g (-4 S.D.), and head circumference of 43.5 cm (-2.5 S.D.).
Fig. 1. Appearance of the child
240
Fig.2. RHG-banded metaphase plate
F. Serville and A. Broustet
Pericentric Inversion and Partial Monosomy 4q
241
Clinical findings included (Fig. 1): round skull; large bregmatic fontanel; prominent forehead; effaced supraorbital ridges; height of the middle part of the face reduced comparatively to the upper and lower facial heights; bilateral epicanthus inversus; microphthalmia and ectopic pupils; anteverted and bulbous nose; broad upper lip without visible philtrum; down-turned corner of mouth; high-arched palate; low-set ears with prominent right fossa; cylindric trunk; narrow pelvis; anterior position of anus; car6 au lait spot on the right knee; and left single palmar crease. There was no cardiac murmur. A Gesell test put the developmental abilities of the patient at about the 10-week level. There was not serious sensory deficiency and the cry was normal. Bone age corresponded to 9--10months. IVP showed left renal and ureteral bifidity. An EEG was normal.
Cytogenetic Investigation L e u c o c y t e culture o f p e r i p h e r a l b l o o d b y s t a n d a r d m e t h o d s revealed 46 c h r o m o somes. T w e n t y - t w o cells were a n a l y s e d with the R H G - b a n d i n g technique (see G r o u c h y a n d T u r l e a u , 1977). One B c h r o m o s o m e was missing a n d there was a s u p e r n u m e r a r y m e t a c e n t r i c C identified as c h r o m o s o m e 4 (Figs. 2 a n d 3). The s t r u c t u r a l r e a r r a n g e m e n t c o u l d be explained b y three b r e a k p o i n t s (Fig. 4). The segment lying between b a n d s 4p16 a n d 4q24 was inverted a n d the segment lying between b a n d s 4q24 a n d 4q32 was deleted. Thus, the overall d e s i g n a t i o n o f the p r o b a n d ' s k a r y o t y p e was: 46,XX,del(4),inv(4)(pter~p16 : : q 2 4 - p 1 6 : : q 3 2 - q t e r ) . The c h r o m o s o m e c o m p l e m e n t o f b o t h p a r e n t s was n o r m a l .
Fig. 3. Chromosome pairs No. 4 from five different cells (RHG-banding)
6--
(--
Fig. 4. Possible location of break points
242
F. Serville and A. Broustet
Comments T w o cases o f p a r t i a l m o n o s o m y 4q have been identified b y b a n d i n g techniques to date: one case b y G o l b u s et al. (1973) a n d the o t h e r b y V a n K e m p e n (1975). T h e clinical features include g r o w t h a n d m e n t a l r e t a r d a t i o n , s h o r t a n t e v e r t e d nose, p a l a t o s c h i s i s , m i c r o g n a t h i a , a n d s u p e r i o r l y p o i n t e d ears. In the two cases the s a m e segment 4 q 3 1 - q t e r is deleted. O u r p a t i e n t ' s k a r y o t y p e s h o w e d an interstitial deletion o f the segment lying b e t w e e n b a n d s 4q24 a n d 4q32. T h e r e f o r e it w o u l d be a p r e s u m p t i o n to c o m p a r e h e r p h e n o t y p e to the p r e v i o u s cases. Acknowledgements. We thank M.-J. Bourdeau and M. Gachet for their skilful laboratory help. Note Added in Proof
At 4 years, the proposita weighted 7000 g and was 79 cm tall; she died as a result of a respiratory infection and the autopsy examination (by N. Frenck) revealed lung edema with atelectasis or emphysema, hypertrophy of heart with patent foramen ovale and endocardial fibro-elastosis of the ventricles and the right atrium.
References Golbus, M. S., Conte, F. A., Daentl, D. L.: Deletion from the long arm of chromosome 4 (46,XX,4q-) associated with congenital anomalies. J. Med. Genet. 10, 83--85 (1973) Grouchy, J. de, Turleau, C.: Atlas des Maladies Chromosomiques. Paris: Expansion Scientifique 1977 Van Kempen, C.: A patient with congenital anomalies and a deletion of the long arm of chromosome 4 [46,XY, del(4)(q31)]. J. Med. Genet. 12, 204--207 (1975) Received June 1, 1977
