J. ment. Defic. Res. (1978) 22, 207
207
CLINICAL OBSERVATIONS IN KLINEFELTER (47,XXY) SYNDROME S.J. FUNDERBURK* and NITA FERJO Mental Retardation and Child Psychiatry Division, Department of Psychiatry and Biobehavioral Science, U.C.L.A. School of Medicine, U.S.A.
INTRODUCTION Developmental speech and language problems have been described in young 47,XXY patients by Campbell, Breuer and Wolman (1973), and Garvey and Mtitton (1973), as well as in 47,XXY individuals detected in newborn screening programmes by Leonard, Landy, Ruddle and Lubs (1974), Puck, Tenne.s, Frankcnburg, Bryant and Robinson (1975), (Jrant and Hamerton (1976), and Tennes, Puck, Ortanakis and Robinson (1977). The purpose ofthe current report is to describe further clinical, educational and behavioural observations in 47,XXY child and young adult psychiatric patients. METHODS EiCTen 47,XXY patients were identified by conventional chromosome analysis of peripheral blood lymphocytes (Arakaki and Sparkes, 1963), during a cytogenetic survey of consecutive child psychiatric outpatients seen between 1968 and 1975 (Crandall, Carrel and Sparkes, 1972). The diagnosi-; was confirmed by chromatin or trypsin-Gienasa banding (Scabright, 1971) studies in all but three instances, where the clinical features were sufficiently consistent with the Klinefelter syndrome to establish the diagnosis. Ten metaphase cells were routinely counted and no demonstrable mosaicism was observed. Three ofthe initial patients (cases 5, 6 and 7 in Table 1) have bjen previously reported (Kivowitz and Corcoran, 1971). It should be noted that behavioural, educational, and psychological evaluations were frequently completed prior to knowledge of the chromosome findings, and only in three ofthe young adult patients (cases 8, 10 and 11 in Table 1) was there a clinical suspicion ofa sex chromosome disorder at the onset of their evaluations. RESULTS Clinical features of the eleven Kiinefelter patients are shown in Table I. As previously reported in young Klinefelter patients by Caldwell and Smith (1972), the mean height percentile in the cases reported here was significantly elevated. However, their mean head circumference percentile was smaller than the respective
•Requests for reprints to: Steve J. Fundrrburk, M.D., Neuropsychiatric Institute, 760 Westwood Plaza, Rm. C8-871, Los Angeles, CA 90024. Received 19th May, 1978
KLINEFELTER SYNDROME
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S. J. FUNDERBURK and NITA FERJO
209
median and three individuals (including one who was the result of a premature birth) had head circumlerences less than the 15th percentile. Interestingly, Hudson and Robinson (1977) recently found a significantly reduced mean head circumference percentile in a prospective study of 47,XXY individuals identified in a ne\vborn screening programme. Brain atrophy was demonstrated in two ofthe patients. In case 10 computerised axial tomography was done following head injury. The study showed mild brain atrophy with high cortical gyri and slightly enlarged lateral ventricles; it wa;; felt that these findings could not have resulted irom the acute head trauma. In case 11 a pneumoencephalogram was done because of grand mal epilepsy and ataxia. The study showed ccrebellar atrophy which was questionably attributed to chronic diphenylhydantoin therapy. Only two ofthe eleven patients reviewed here had no dysmorphic features and no neurological findings. Presenting behavioural problems in our eleven patients are summarised in Table 2. Three patients had chronic faecal retention and soiling and two more had unspecified and transient constipation. To the authors' knowledge, psyehogenic inegacolon lias not previously been reported as a common problem in Klinefelter patients, although another 47,XXY patient with chronic childhood faecal retention and soiling has recently been identified (personal communication from Arthur Robinson, M.D., 1977). Results of the verbal and performance scores from the Wechsler Intelligence 'I'ests were available for comparison on eight patients. The mean verbal, performance, and full scale scores, 93.6, 93.0 and 92.7, respectively, were nearly identical. Similariy, there was no particular pattern within the verbal or performance subtest scores. In contrast to these test results, the developmental histories and language evaluations in our patients revealed a high frequency of speech and language prol)lems. Four of eight patients presented under seventeen years of age had delayed
Table 2 Presenting problems in eleven 47,XXT
School underachieveineiit . Withdrawal, apathy . Impulsive, physically aggressive Faecal retention, soiling, constipation Enuresis . . . . . Truancy . . . . . Tics . . . . . . Headaches . . . . Fire-setting . . . . Lying Stealing . . . . . Nightmares . . . .
patients Xo. pis 9 8 6 5 2 2 3
2 2 1
I 1
210
KLINEFELTER SYNDROME
language development and three had received speech therapy. The Illinois Test of Psycholinguistic Abilities, which measures visual and auditory components of receptive and expressive language development, characterised the expressive deficits in o\ir two youngest six-year-old patients. They both had normal auditory and visual reception and normal visual association, but scored low on auditory association, grammatic closure, and verbal expression. Examples of auditory association errors were as follows; when asked to complete the phrase, "Here is a child, here are two {children)", one patient replied, "Two childs"; or when asked to complete, "A man may be a king, a woman may be a [queen]", the patient replied, "A girl". Limited verbal expression was evident in describing objects such as a block where the child should give statements like "green, wood, or to build with". Instead, one patient responded by repeating the word "block" several times. That one ofthe six-year-old patients was aware of his limited language was evident when he offered, "You know it's hard for me to say the things that 1 think". Similar findings were present in three ofthe patients presenting at over seventeen years of age. Two had limited expressive language and the third had a low abstraction score on the Shipley-Hartford Intelligence Scale. Androgen treatment was attempted in only one of the patients reported here. Case 10 was diagnosed at age eighteen as having possible hysterical psychosis. Although his serum testosterone level was in the normal adult male range, a trial of monthly test sterone injections was initiated. After several months, his behavioural symptoms appeared to worsen and the patient withdrew from further treatment. DISCUSSION Early studies of adult Klinefelter syndrome individuals suggested "congenital dyslexia and congenital speech apraxia" {Money, 1963). Data from a more recent study of thirty-four adult Klinefelter patients, when pooled with data from previous similar studies, revealed a small but consistent lowering of the mean verbal IQ, scores relative to performance I Q scores (Theilgaard, 1972). In the thirly-four individuals examined in that study, there appeared to be a limited range of imagination and expression in language. It was concluded that speech and language problems, though not always reflected in intelligence test scores, are common among adult 47,XXY patients. Results of the current study also suggest an early onset of concreteness, poor abstraction, limited range of expressivity, and problems in speech production, all of v\ hieh may contribute to later under-achievement, social maladaptiveness, and even the apparent schizophrenia (Sorenson and Nielsen, 1977) present in sonic adult Klinefelter patients. This theory is supported by suggestive evidence that cognition and memory may be mediated in part through language (Herriot, Green and McConkey, 1973). Although the current report involved a select group of KlineOltcr patients, pooled data from twd prospective studies in Denver and Winnijx-g showed early speech and language problems in nine of twenty 47,XXY individuals detected in newborn screening programmes (Puck et ai, 1975; Grant and Hamerton, 1976; Tennes et al., 1977). It was stiggcsted in the Denver study thai elevated develop-
S. J. FUNDERBURK and NITA FERJO
211
mental risks in the 47,XXY individuals may be minimised by appropriate familial and environmental situations, as was illustrated in one of their cases with early educational and speech intervention (Puck et aL, 1975). More longitudinal evaluations are needed to characteiisc the extent of the developmental and behavioural problems in 47,XXY individuals. In addition, data obtained from the study of select groups of Klinefelter patients may be complementary to prospective studies, since there has been the recent criticism ofa possible "self-fulfilling prophecy" for later developmental problems when infants with sex chromosome abnormalities are detected in newborn screening programmes (personal communication from Arthur Robinson, M.D.). Results ofthe current study concur with previous reports that 47,XXY individuals may have early language and speech problems, and it is anticipated that appropriate educational intervention might reverse or diminish some of the long-term intellectual and ]>sychiatric problems present in some of these individuals. SUMMARY The elinical and behavioural findings in eleven young 47,XXY psychiatric patients are described. There were several unexpected features including chronic faecal retention with soiling (encopresis) in three patients, a reduced head circumference (tenth percentile or less) in three patients, and either cerebral or cerebeliar atrophy in two patients. Although there was no discrepancy between mean verbal and performance IQ. scores, eight of the eleven patients had either poor expressive language or a history of speech and language problems. AU eight patients with language deficits had normal intellectual capacity (IQ. scores greater than 80), suggesting a potential for early Ijchavioural and educational intervention in these cases. ACKNOWLEDGEMENTS This research supported in part by the U.C.L.A. Mental Retardation/Child Psychiatry Division; and PHS grants MCH-927, 59P-45192/9-07, HD-04612, and HD-05615. REFERENCES ARAKAKI, D . T . and SPARKES, R. S. (1963) Microtechnique for culturing leukocytes from wholr blood, Cytogenetics 2. 57. CALDWELL. P. D. and SMITH, D . W . (1972) The XXY (Klinefelter) syndrome m childhood:
Detection and treatment. J. Pediat. 80, 250. CAMPBELL, M . , BREUER, H . and WOLMAN, S. R . (1973) The interplay of biological and
environmental factors in a preschool-age patient with KHnefelter's syndrome. Pedtat. 52 29 CRANDALL," B . F . , CARREL, R . E . and SPARKES, R . S. (1972) Chromosome findings in 700
children referred to a psychiatric clinic. J . Pediat. 80, 62. GARVEY, M . and MurroN, D. E. (1973) Sex chromasome aberrations and speech development. Arch. dis. Child. 48, 937. GRANT, W . W . and HAMERTON, J. L. (1976) A cytogenetic survey of 14,069 newborn mfants. II. Preliminary clinical findings on children with sex chromosome anomalies. Clw. Genet. 10, 285.
KLINEFELTER SYNDROME HERKIOT, P., GKEEN, J . M . and MCCONKEV, R . (1973) Organisation andmemory; a review, and a
project in subnormality. P. Mittler (Ed.). London: Methucn & Co., Ltd. HUDSON, M . J. and ROBINSON, A. (1977) Physical characteristics ol"47,XXV boys and 47,XXX girls followed from birth. Am. J. human Genet. 29. 57A. KivowiTZ,.J. and CORCORAN,./. (1971) Theoretical and practical consideralions in Klinefelter's syndrome in children. A repoit of three cases of 47,XXY. 7. Amer. Acad. Child Psychiat. 10 700. LEONARD, M . !•., L.\NDY, (J.., RUDDLE, V. H. and LUBS, H . A. (1974) Early development of
children with abnornialities ofthe sex chromosomes; A prospective study. Pediat. 54, 208. MONEY, J. (1963) Cytogenetic and psychosoeial incongruities with a note on space-form blindness. Amer.J. P.sychol. 119, 820. PUCK, M . , TENNES, K . . FRANKENBURG, W . , BRYANI , K. and ROBINSON, A. (1975) Early
childhooddevelopment of four boys with 47,XXV karyotype. C/m. Pediat. 7,8. SEABRIGHT. M . (1971) Rapid banding technique for human chromosomes. I^ncel 2. 971. SoRENSEN, K. and NIELSEN, J. (1977} Twcity psychotic males with Klinefelter's syndrome. Acta Psvchiat. Scand. 56, 249. TENNES, K . , FUCK, M . , ORFANAKIS, D . and ROBINSON. A. (1977) The early childhood develop-
ment of 17 boys with sex chromosome anomalies: A prospective study. Pediat. 59, 574. THEILGAARD, A. (1972) Cognitive style and gender role in persons with sex chromosome aberrations. Dan. med. Bull. 19. 276.
207
CLINICAL OBSERVATIONS IN KLINEFELTER (47,XXY) SYNDROME S.J. FUNDERBURK* and NITA FERJO Mental Retardation and Child Psychiatry Division, Department of Psychiatry and Biobehavioral Science, U.C.L.A. School of Medicine, U.S.A.
INTRODUCTION Developmental speech and language problems have been described in young 47,XXY patients by Campbell, Breuer and Wolman (1973), and Garvey and Mtitton (1973), as well as in 47,XXY individuals detected in newborn screening programmes by Leonard, Landy, Ruddle and Lubs (1974), Puck, Tenne.s, Frankcnburg, Bryant and Robinson (1975), (Jrant and Hamerton (1976), and Tennes, Puck, Ortanakis and Robinson (1977). The purpose ofthe current report is to describe further clinical, educational and behavioural observations in 47,XXY child and young adult psychiatric patients. METHODS EiCTen 47,XXY patients were identified by conventional chromosome analysis of peripheral blood lymphocytes (Arakaki and Sparkes, 1963), during a cytogenetic survey of consecutive child psychiatric outpatients seen between 1968 and 1975 (Crandall, Carrel and Sparkes, 1972). The diagnosi-; was confirmed by chromatin or trypsin-Gienasa banding (Scabright, 1971) studies in all but three instances, where the clinical features were sufficiently consistent with the Klinefelter syndrome to establish the diagnosis. Ten metaphase cells were routinely counted and no demonstrable mosaicism was observed. Three ofthe initial patients (cases 5, 6 and 7 in Table 1) have bjen previously reported (Kivowitz and Corcoran, 1971). It should be noted that behavioural, educational, and psychological evaluations were frequently completed prior to knowledge of the chromosome findings, and only in three ofthe young adult patients (cases 8, 10 and 11 in Table 1) was there a clinical suspicion ofa sex chromosome disorder at the onset of their evaluations. RESULTS Clinical features of the eleven Kiinefelter patients are shown in Table I. As previously reported in young Klinefelter patients by Caldwell and Smith (1972), the mean height percentile in the cases reported here was significantly elevated. However, their mean head circumference percentile was smaller than the respective
•Requests for reprints to: Steve J. Fundrrburk, M.D., Neuropsychiatric Institute, 760 Westwood Plaza, Rm. C8-871, Los Angeles, CA 90024. Received 19th May, 1978
KLINEFELTER SYNDROME
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S. J. FUNDERBURK and NITA FERJO
209
median and three individuals (including one who was the result of a premature birth) had head circumlerences less than the 15th percentile. Interestingly, Hudson and Robinson (1977) recently found a significantly reduced mean head circumference percentile in a prospective study of 47,XXY individuals identified in a ne\vborn screening programme. Brain atrophy was demonstrated in two ofthe patients. In case 10 computerised axial tomography was done following head injury. The study showed mild brain atrophy with high cortical gyri and slightly enlarged lateral ventricles; it wa;; felt that these findings could not have resulted irom the acute head trauma. In case 11 a pneumoencephalogram was done because of grand mal epilepsy and ataxia. The study showed ccrebellar atrophy which was questionably attributed to chronic diphenylhydantoin therapy. Only two ofthe eleven patients reviewed here had no dysmorphic features and no neurological findings. Presenting behavioural problems in our eleven patients are summarised in Table 2. Three patients had chronic faecal retention and soiling and two more had unspecified and transient constipation. To the authors' knowledge, psyehogenic inegacolon lias not previously been reported as a common problem in Klinefelter patients, although another 47,XXY patient with chronic childhood faecal retention and soiling has recently been identified (personal communication from Arthur Robinson, M.D., 1977). Results of the verbal and performance scores from the Wechsler Intelligence 'I'ests were available for comparison on eight patients. The mean verbal, performance, and full scale scores, 93.6, 93.0 and 92.7, respectively, were nearly identical. Similariy, there was no particular pattern within the verbal or performance subtest scores. In contrast to these test results, the developmental histories and language evaluations in our patients revealed a high frequency of speech and language prol)lems. Four of eight patients presented under seventeen years of age had delayed
Table 2 Presenting problems in eleven 47,XXT
School underachieveineiit . Withdrawal, apathy . Impulsive, physically aggressive Faecal retention, soiling, constipation Enuresis . . . . . Truancy . . . . . Tics . . . . . . Headaches . . . . Fire-setting . . . . Lying Stealing . . . . . Nightmares . . . .
patients Xo. pis 9 8 6 5 2 2 3
2 2 1
I 1
210
KLINEFELTER SYNDROME
language development and three had received speech therapy. The Illinois Test of Psycholinguistic Abilities, which measures visual and auditory components of receptive and expressive language development, characterised the expressive deficits in o\ir two youngest six-year-old patients. They both had normal auditory and visual reception and normal visual association, but scored low on auditory association, grammatic closure, and verbal expression. Examples of auditory association errors were as follows; when asked to complete the phrase, "Here is a child, here are two {children)", one patient replied, "Two childs"; or when asked to complete, "A man may be a king, a woman may be a [queen]", the patient replied, "A girl". Limited verbal expression was evident in describing objects such as a block where the child should give statements like "green, wood, or to build with". Instead, one patient responded by repeating the word "block" several times. That one ofthe six-year-old patients was aware of his limited language was evident when he offered, "You know it's hard for me to say the things that 1 think". Similar findings were present in three ofthe patients presenting at over seventeen years of age. Two had limited expressive language and the third had a low abstraction score on the Shipley-Hartford Intelligence Scale. Androgen treatment was attempted in only one of the patients reported here. Case 10 was diagnosed at age eighteen as having possible hysterical psychosis. Although his serum testosterone level was in the normal adult male range, a trial of monthly test sterone injections was initiated. After several months, his behavioural symptoms appeared to worsen and the patient withdrew from further treatment. DISCUSSION Early studies of adult Klinefelter syndrome individuals suggested "congenital dyslexia and congenital speech apraxia" {Money, 1963). Data from a more recent study of thirty-four adult Klinefelter patients, when pooled with data from previous similar studies, revealed a small but consistent lowering of the mean verbal IQ, scores relative to performance I Q scores (Theilgaard, 1972). In the thirly-four individuals examined in that study, there appeared to be a limited range of imagination and expression in language. It was concluded that speech and language problems, though not always reflected in intelligence test scores, are common among adult 47,XXY patients. Results of the current study also suggest an early onset of concreteness, poor abstraction, limited range of expressivity, and problems in speech production, all of v\ hieh may contribute to later under-achievement, social maladaptiveness, and even the apparent schizophrenia (Sorenson and Nielsen, 1977) present in sonic adult Klinefelter patients. This theory is supported by suggestive evidence that cognition and memory may be mediated in part through language (Herriot, Green and McConkey, 1973). Although the current report involved a select group of KlineOltcr patients, pooled data from twd prospective studies in Denver and Winnijx-g showed early speech and language problems in nine of twenty 47,XXY individuals detected in newborn screening programmes (Puck et ai, 1975; Grant and Hamerton, 1976; Tennes et al., 1977). It was stiggcsted in the Denver study thai elevated develop-
S. J. FUNDERBURK and NITA FERJO
211
mental risks in the 47,XXY individuals may be minimised by appropriate familial and environmental situations, as was illustrated in one of their cases with early educational and speech intervention (Puck et aL, 1975). More longitudinal evaluations are needed to characteiisc the extent of the developmental and behavioural problems in 47,XXY individuals. In addition, data obtained from the study of select groups of Klinefelter patients may be complementary to prospective studies, since there has been the recent criticism ofa possible "self-fulfilling prophecy" for later developmental problems when infants with sex chromosome abnormalities are detected in newborn screening programmes (personal communication from Arthur Robinson, M.D.). Results ofthe current study concur with previous reports that 47,XXY individuals may have early language and speech problems, and it is anticipated that appropriate educational intervention might reverse or diminish some of the long-term intellectual and ]>sychiatric problems present in some of these individuals. SUMMARY The elinical and behavioural findings in eleven young 47,XXY psychiatric patients are described. There were several unexpected features including chronic faecal retention with soiling (encopresis) in three patients, a reduced head circumference (tenth percentile or less) in three patients, and either cerebral or cerebeliar atrophy in two patients. Although there was no discrepancy between mean verbal and performance IQ. scores, eight of the eleven patients had either poor expressive language or a history of speech and language problems. AU eight patients with language deficits had normal intellectual capacity (IQ. scores greater than 80), suggesting a potential for early Ijchavioural and educational intervention in these cases. ACKNOWLEDGEMENTS This research supported in part by the U.C.L.A. Mental Retardation/Child Psychiatry Division; and PHS grants MCH-927, 59P-45192/9-07, HD-04612, and HD-05615. REFERENCES ARAKAKI, D . T . and SPARKES, R. S. (1963) Microtechnique for culturing leukocytes from wholr blood, Cytogenetics 2. 57. CALDWELL. P. D. and SMITH, D . W . (1972) The XXY (Klinefelter) syndrome m childhood:
Detection and treatment. J. Pediat. 80, 250. CAMPBELL, M . , BREUER, H . and WOLMAN, S. R . (1973) The interplay of biological and
environmental factors in a preschool-age patient with KHnefelter's syndrome. Pedtat. 52 29 CRANDALL," B . F . , CARREL, R . E . and SPARKES, R . S. (1972) Chromosome findings in 700
children referred to a psychiatric clinic. J . Pediat. 80, 62. GARVEY, M . and MurroN, D. E. (1973) Sex chromasome aberrations and speech development. Arch. dis. Child. 48, 937. GRANT, W . W . and HAMERTON, J. L. (1976) A cytogenetic survey of 14,069 newborn mfants. II. Preliminary clinical findings on children with sex chromosome anomalies. Clw. Genet. 10, 285.
KLINEFELTER SYNDROME HERKIOT, P., GKEEN, J . M . and MCCONKEV, R . (1973) Organisation andmemory; a review, and a
project in subnormality. P. Mittler (Ed.). London: Methucn & Co., Ltd. HUDSON, M . J. and ROBINSON, A. (1977) Physical characteristics ol"47,XXV boys and 47,XXX girls followed from birth. Am. J. human Genet. 29. 57A. KivowiTZ,.J. and CORCORAN,./. (1971) Theoretical and practical consideralions in Klinefelter's syndrome in children. A repoit of three cases of 47,XXY. 7. Amer. Acad. Child Psychiat. 10 700. LEONARD, M . !•., L.\NDY, (J.., RUDDLE, V. H. and LUBS, H . A. (1974) Early development of
children with abnornialities ofthe sex chromosomes; A prospective study. Pediat. 54, 208. MONEY, J. (1963) Cytogenetic and psychosoeial incongruities with a note on space-form blindness. Amer.J. P.sychol. 119, 820. PUCK, M . , TENNES, K . . FRANKENBURG, W . , BRYANI , K. and ROBINSON, A. (1975) Early
childhooddevelopment of four boys with 47,XXV karyotype. C/m. Pediat. 7,8. SEABRIGHT. M . (1971) Rapid banding technique for human chromosomes. I^ncel 2. 971. SoRENSEN, K. and NIELSEN, J. (1977} Twcity psychotic males with Klinefelter's syndrome. Acta Psvchiat. Scand. 56, 249. TENNES, K . , FUCK, M . , ORFANAKIS, D . and ROBINSON. A. (1977) The early childhood develop-
ment of 17 boys with sex chromosome anomalies: A prospective study. Pediat. 59, 574. THEILGAARD, A. (1972) Cognitive style and gender role in persons with sex chromosome aberrations. Dan. med. Bull. 19. 276.
