PSYCHOLOGICAL CHARACTERISTICS OF SOTOS SYNDROME S. C. Rutter T. R. P. Cole
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Sotos syndrome, or cerebral gigantism, was first described in 1964 by Sotos and colleagues. The disorder, usually detectable from early childhood, is generally described in terms of its well-documented physical characteristics. Children are large for gestational age and have accelerated growth, particularly in infancy (Wit et al. 1985). This is usually associated with advanced skeletal maturation (Cole and Hughes 1990), so it may be rare for people with Sotos syndrome to reach gigantic proportions in adulthood (Hughes and Cole 1991), although such a phenomenon has been described. There are a number of distinctive dysmorphic features, including a high forehead, frontal bossing, prominent jaw, hypertelorism and antimongoloid slant of the palpebral fissures, together with a high-arched palate (Dodge et al. 1983). Although all the. characteristics do not occur in every child, children with Sotos syndrome have been noted to bear a striking resemblance to one another. The countenance is quite distinctive, especially in the earlier years (Cole and Hughes 1990). At present Sotos syndrome is thought to be rare, and estimates of the ratio of males to females vary (Mace and Gorlin 1970, Jaeken et al. 1972, Hughes and Cole 1991). While there is general agreement about the physical manifestations of the dis-
order, the pathogenesis of Sotos syndrome remains unclear. A number of biochemical and endocrinological studies have produced inconclusive results. Zonana et al. (1977) and Winship (1985) have suggested that the disorder is inherited as an autosomal dominant trait, while Boman and Nilson (1980) described two brothers and suggested autosomal recessive inheritance: however, the vast majority of cases appear to be sporadic (Hughes and Cole 1991). There have also been several reports in recent years of children diagnosed as having Sotos syndrome who also have fragile-x sites (Fryns 1984, Beemer et al. 1986). However, since these reports many children with Sotos syndrome have been karyotyped and have not shown the same fragile sites, which suggests that the two conditions are separate. A small number of studies have looked at the psychological characteristics of children with Sotos syndrome. The results have been varied. Jaeken et al. (1972) reviewed the literature available on 80 children with the syndrome and showed that 83 per cent had some degree of learning difficulty. Bloom (1983) studied a group of 10 children and suggested that previous studies had over-estimated the level of cognitive disability. Varley and Crnic (1984), in a similar-sized study, found that while all their children fell
within the learning disability range, there was a wide range of variability. They concluded that the most characteristic pattern was one of generalised developmental retardation of varying severity. They also isolated adaptive social functioning as being an area of specific difficulty. Other studies have identified specific delays in language and motor development (Sotos et al. 1977) and attention deficits (Bloom 1983), while anecdotal evidence provides an indication that children with Sotos syndrome may have specific difficulties with mathematics, writing and creative tasks, concurrent with normal or advanced reading and spelling ability. Morrow et al. (1990) have described a single child with Sotos syndrome, of normal intelligence but with an autistic disorder.
(Neale 1966) and the Schonell Graded Word Reading Test (Schonell 1950). Emotional and behavioural disturbance was assessed with the Rutter Questionnaires (Rutter 1967, Rutter et al. 1970), which consist of a series of behavioural descriptions that are indicative of disturbance. In addition to these formal instruments of assessment, further information was gathered by means of a semi-structured interview with the parent(s) of each child. They were encouraged to describe their child and to discuss any particular difficulties that they attributed to Sotos syndrome. A question checklist, based on information available from the Sotos Syndrome Support Group, ensured that the same range of topics was covered at each interview.
Method The subjects were 16 children (seven girls, nine boys) whose ages ranged from 5 years 11 months to 14 years 9 months (mean 9 years 4 months). The sample was drawn from children who had already been included in the Sotos syndrome survey being conducted at the Institute of Medical Genetics for Wales. Each child had been found positive for all the following diagnostic criteria, defined by Hughes and Cole (1991): (1) a period of accelerated growth in early childhood (height above 97th centile for at least one year); (2) distinctive facial features; (3) advanced bone-age at some time in childhood, e.g. above 90th centile using TW2 standards (Tanner et al. 1975); and (4) descriptive evidence of early developmental delay, with particular emphasis on delay in reaching motor and verbal milestones.
Results Cognitive abilities
Assessments The level of cognitive functioning was assessed with the Wechsler Intelligence Scale for Children (WISC-R) (Wechsler 1976) in 13 cases and with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) (Wechsler 1967) in three cases. Reading attainment was assessed with the Neale Analysis of Reading Ability
One child refused to co-operate with the testing procedure. The Full-scale IQs for the other 15 children on the WISC-R (13) or WIPPSI (two), ranged from 54 to 96 (mean 73.8). As the two measures are highly correlated (Full-scale IQ = 0.95; Verbal IQ = 0.96; Performance IQ = 0.83) (Wechsler 1974), the distribution of scores are presented together. Five children fell into the moderate range of learning difficulties (IQ 51 to 70); four were within Wechsler’s borderline range (IQ 70 to 79); four were within the low-average range (IQ 80 to 89); and two were within the average range (IQ 90 to 109). Verbal IQS ranged from 47 to 102 (mean 76-93) and Performance IQs from 51 and 101 (mean 74.6). The sums of the scaled scores on the WISC-R Verbal and Performance scales were compared statistically, but there was no significant difference between the two. There was, however, a broad range of Verbal-Performance discrepancies across the 13 children who were tested (range 0 to 28 points). The children’s performance on the individual subtests of the WISC-R was also examined. It is of note that while there was great variability among the children’s scores for most of the individual subtests (range 1 to 13), their scoring was quite consistent on the Object Assembly subtest (range 6 to 10).
2ct
899
TABLE I Behavioural disturbance on Rutter Parent and Teacher Scales
uj
Parent Scale (N = 16) Deviant score (13 +) Neurotic Antisocial Undifferentiated
i;
Teacher Scale (N= 14) Deviant score (9+) Neurotic Antisocial Undifferentiated
ti
u
12 (75.0) 7 (43.8) 4 (25.0) 1 (6.3) 7 (50.0) 5 (35.7) 2 (14.3)
-
vl
c 0
Reading attainment Twelve of the children were able to attain some score on the Neale and Schonell tests. Of the remaining four, three were unable to read and one refused to co-operate. The 12 readers had a mean chronological age of 10 years 4 months (range 7 years 3 months to 14 years 11 months). The mean Full-scale IQ of this group was 74.5. Their mean age for Reading Accuracy was 8 years 3 months (range 6 years 8 months to 11 years 11 months) and for Reading Comprehension was 7 years 8 months (range 6 years 4 months to 12 years) on the Neale test. To assess the relationship between reading attainment and cognitive ability, the Reading Accuracy and Reading Comprehension ages were predicted for all the readers between the ages of six and 12 years (nine children). When the predicted ages were compared with the observed scores, two children had discrepant Reading Accuracy ages and two had discrepant Reading Comprehension ages (less than 20 per cent of the population have comparable or greater discrepancies). The mean reading age on the Schonell measure was 8 years 2 months (range 5 years 9 months to 13 years 1 month).
900
Behavioural and emotional adjustment The Rutter Questionnaires were completed by the parents of all 16 children and by the teachers of 14 (Table I). On the Parent Questionnaire, 12 children had a score on or above the cut-off of 13 points, which was used to identify children with a high level of reported problem behaviours
(range 2 to 42, mean 20-4). On the Teacher Questionnaire, half the children had scores on or above the cut-off score of 9 points (range 2 to 23, mean 8.7). There was a significant difference between the summed scores of the two scales(t=4-12, df= 13,p
N 0
m W m W
m
PD
c
s
E E
2E 4
898
Sotos syndrome, or cerebral gigantism, was first described in 1964 by Sotos and colleagues. The disorder, usually detectable from early childhood, is generally described in terms of its well-documented physical characteristics. Children are large for gestational age and have accelerated growth, particularly in infancy (Wit et al. 1985). This is usually associated with advanced skeletal maturation (Cole and Hughes 1990), so it may be rare for people with Sotos syndrome to reach gigantic proportions in adulthood (Hughes and Cole 1991), although such a phenomenon has been described. There are a number of distinctive dysmorphic features, including a high forehead, frontal bossing, prominent jaw, hypertelorism and antimongoloid slant of the palpebral fissures, together with a high-arched palate (Dodge et al. 1983). Although all the. characteristics do not occur in every child, children with Sotos syndrome have been noted to bear a striking resemblance to one another. The countenance is quite distinctive, especially in the earlier years (Cole and Hughes 1990). At present Sotos syndrome is thought to be rare, and estimates of the ratio of males to females vary (Mace and Gorlin 1970, Jaeken et al. 1972, Hughes and Cole 1991). While there is general agreement about the physical manifestations of the dis-
order, the pathogenesis of Sotos syndrome remains unclear. A number of biochemical and endocrinological studies have produced inconclusive results. Zonana et al. (1977) and Winship (1985) have suggested that the disorder is inherited as an autosomal dominant trait, while Boman and Nilson (1980) described two brothers and suggested autosomal recessive inheritance: however, the vast majority of cases appear to be sporadic (Hughes and Cole 1991). There have also been several reports in recent years of children diagnosed as having Sotos syndrome who also have fragile-x sites (Fryns 1984, Beemer et al. 1986). However, since these reports many children with Sotos syndrome have been karyotyped and have not shown the same fragile sites, which suggests that the two conditions are separate. A small number of studies have looked at the psychological characteristics of children with Sotos syndrome. The results have been varied. Jaeken et al. (1972) reviewed the literature available on 80 children with the syndrome and showed that 83 per cent had some degree of learning difficulty. Bloom (1983) studied a group of 10 children and suggested that previous studies had over-estimated the level of cognitive disability. Varley and Crnic (1984), in a similar-sized study, found that while all their children fell
within the learning disability range, there was a wide range of variability. They concluded that the most characteristic pattern was one of generalised developmental retardation of varying severity. They also isolated adaptive social functioning as being an area of specific difficulty. Other studies have identified specific delays in language and motor development (Sotos et al. 1977) and attention deficits (Bloom 1983), while anecdotal evidence provides an indication that children with Sotos syndrome may have specific difficulties with mathematics, writing and creative tasks, concurrent with normal or advanced reading and spelling ability. Morrow et al. (1990) have described a single child with Sotos syndrome, of normal intelligence but with an autistic disorder.
(Neale 1966) and the Schonell Graded Word Reading Test (Schonell 1950). Emotional and behavioural disturbance was assessed with the Rutter Questionnaires (Rutter 1967, Rutter et al. 1970), which consist of a series of behavioural descriptions that are indicative of disturbance. In addition to these formal instruments of assessment, further information was gathered by means of a semi-structured interview with the parent(s) of each child. They were encouraged to describe their child and to discuss any particular difficulties that they attributed to Sotos syndrome. A question checklist, based on information available from the Sotos Syndrome Support Group, ensured that the same range of topics was covered at each interview.
Method The subjects were 16 children (seven girls, nine boys) whose ages ranged from 5 years 11 months to 14 years 9 months (mean 9 years 4 months). The sample was drawn from children who had already been included in the Sotos syndrome survey being conducted at the Institute of Medical Genetics for Wales. Each child had been found positive for all the following diagnostic criteria, defined by Hughes and Cole (1991): (1) a period of accelerated growth in early childhood (height above 97th centile for at least one year); (2) distinctive facial features; (3) advanced bone-age at some time in childhood, e.g. above 90th centile using TW2 standards (Tanner et al. 1975); and (4) descriptive evidence of early developmental delay, with particular emphasis on delay in reaching motor and verbal milestones.
Results Cognitive abilities
Assessments The level of cognitive functioning was assessed with the Wechsler Intelligence Scale for Children (WISC-R) (Wechsler 1976) in 13 cases and with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) (Wechsler 1967) in three cases. Reading attainment was assessed with the Neale Analysis of Reading Ability
One child refused to co-operate with the testing procedure. The Full-scale IQs for the other 15 children on the WISC-R (13) or WIPPSI (two), ranged from 54 to 96 (mean 73.8). As the two measures are highly correlated (Full-scale IQ = 0.95; Verbal IQ = 0.96; Performance IQ = 0.83) (Wechsler 1974), the distribution of scores are presented together. Five children fell into the moderate range of learning difficulties (IQ 51 to 70); four were within Wechsler’s borderline range (IQ 70 to 79); four were within the low-average range (IQ 80 to 89); and two were within the average range (IQ 90 to 109). Verbal IQS ranged from 47 to 102 (mean 76-93) and Performance IQs from 51 and 101 (mean 74.6). The sums of the scaled scores on the WISC-R Verbal and Performance scales were compared statistically, but there was no significant difference between the two. There was, however, a broad range of Verbal-Performance discrepancies across the 13 children who were tested (range 0 to 28 points). The children’s performance on the individual subtests of the WISC-R was also examined. It is of note that while there was great variability among the children’s scores for most of the individual subtests (range 1 to 13), their scoring was quite consistent on the Object Assembly subtest (range 6 to 10).
2ct
899
TABLE I Behavioural disturbance on Rutter Parent and Teacher Scales
uj
Parent Scale (N = 16) Deviant score (13 +) Neurotic Antisocial Undifferentiated
i;
Teacher Scale (N= 14) Deviant score (9+) Neurotic Antisocial Undifferentiated
ti
u
12 (75.0) 7 (43.8) 4 (25.0) 1 (6.3) 7 (50.0) 5 (35.7) 2 (14.3)
-
vl
c 0
Reading attainment Twelve of the children were able to attain some score on the Neale and Schonell tests. Of the remaining four, three were unable to read and one refused to co-operate. The 12 readers had a mean chronological age of 10 years 4 months (range 7 years 3 months to 14 years 11 months). The mean Full-scale IQ of this group was 74.5. Their mean age for Reading Accuracy was 8 years 3 months (range 6 years 8 months to 11 years 11 months) and for Reading Comprehension was 7 years 8 months (range 6 years 4 months to 12 years) on the Neale test. To assess the relationship between reading attainment and cognitive ability, the Reading Accuracy and Reading Comprehension ages were predicted for all the readers between the ages of six and 12 years (nine children). When the predicted ages were compared with the observed scores, two children had discrepant Reading Accuracy ages and two had discrepant Reading Comprehension ages (less than 20 per cent of the population have comparable or greater discrepancies). The mean reading age on the Schonell measure was 8 years 2 months (range 5 years 9 months to 13 years 1 month).
900
Behavioural and emotional adjustment The Rutter Questionnaires were completed by the parents of all 16 children and by the teachers of 14 (Table I). On the Parent Questionnaire, 12 children had a score on or above the cut-off of 13 points, which was used to identify children with a high level of reported problem behaviours
(range 2 to 42, mean 20-4). On the Teacher Questionnaire, half the children had scores on or above the cut-off score of 9 points (range 2 to 23, mean 8.7). There was a significant difference between the summed scores of the two scales(t=4-12, df= 13,p
