© Hogrefe & Huber Publishers, 1992
This article was originally published in European Child and Adolescent Psychiatry, Vol. 1, No. 2, pp. 89-99, April 1992. It is provided to Asperger Syndrome Coalition of the United States, Inc. for use on its website with the express written permission of Dr. Dietrich Steinkopff Verlag. It may be downloaded and printed for personal reference, but not otherwise copied, altered in any way or transmitted to others (unless explicitly stated otherwise) without the written permission of Dr. Dietrich Steinkopff Verlag. Hypertext links to other Web locations do not constitute any endorsement or authorisation by Dr. Dietrich Steinkopff Verlag.

Abstract:

Six girls aged 6-10 years meeting criteria for autistic disorder are presented. They were all high-functioning in that they had IQs in the 60-100 range and spoke in complicated sentences. Their clinical picture had not led a variety of specialists to consider an autism diagnosis before age 6 years in spite of the fact that they had shown mild motor delays, uncharacteristic developmental deviance and social, communicative and imaginative deficits already before age 2 years in all cases. It is suggested that the autism phenotype might be different in girls as compared with boys. It is further speculated that if female cases such as those described - and others given a whole host of different diagnostic labels - were only considered for an autism diagnosis, the male:female ratio traditionally encountered in autism might drop considerably.

Introduction

Autism (Kanner, 1943; APA, 1980, 1987; Rutter, 1978; Coleman & Gillberg, 1985) and Asperger syndrome (Asperger, 1944; Wing, 1981a; Gillberg & Gillberg, 1989) – ever since they were first described – have been thought of as disorders affecting males much more commonly than females (Wing, 1981b). This has been held to be particularly true of so called high functioning cases. Girls with "typical" problems on the autism spectrum are reported to be relatively more common in the lowest range of intellectual functioning, boy:girl ratios in the most severely retarded groups being in the range of 2:1 rather than the much cited ratio of 3-4:1 for the autism group as a whole (Rutter, 1985) and 9-10:1 for the Asperger group (Rutter, 1985; Gillberg, 1989).

Some of the features of autism, such as insistence on sameness, obsessional interests and pre-occupation with objects or parts of objects as well as relatively superior visuospatial skills might be thought of as exaggerations of male characteristics. This, in the present state of our knowledge, is slightly speculative, but there is clear evidence that males as a group are superior in visuospatial skills (Maccoby & Jacklin, 1980). The communication deficit encountered in autism, similarly, might be conceptualized as a pathological exaggeration of male language development, which appears to be slower and more vulnerable than female language development (Wing, 1981b). The deficiencies in the field of social imitation/communication could also be attributable to pathology in an area where males are generally believed to have less well-developed skills than females, even though it seems that at this time there is no strong empirical evidence for a sex difference in this respect.

Wing (1981b) suggested that autism as a syndrome (and other autisticlike conditions) might be conceptualized as a pathological exaggeration of the traits encountered in men generally. She further proposed that, were this to be the case, the insult to the central nervous system necessary and sufficient to produce autism would have to be considerably milder in males than in females. She upheld this hypothesis by presenting data on sex ratios in autism and autisticlike conditions at varying degrees of intellectual functioning. She was able to show that in the severely brain-damaged population with autism (or pronounced autistic features, including the "triad" of social, communication and imagination impairments (Wing & Gould, 1979)) there is a disproportionately high number of girls as compared with the whole autism/autisticlike group regardless of brain damage/severity of mental retardation. In this, she has since been partly supported by findings from other studies (Tsai et al., 1981; Lord et al., 1982; Lord & Schopler, 1985; Steffenburg & Gillberg, 1986; Gillberg et al., 1991). Wing thought that the variation of sex ratios with IQ could indicate that in males autism may often be the result of genetic factors, whereas in females, severe brain damage may be a relatively much more common cause.

In our centre, for many years now, we have come across girls who have severe social and communication impairments – and restrictions in their behavioural repertoire – but who do not clinically present with the picture usually associated with autism. In childhood, they often fulfill criteria for autistic disorder (APA, 1987) – and sometimes for infantile autism (APA, 1980) – but, as they grow up, they gradually tend to differ considerably from same-aged males with diagnoses on the autism spectrum. Even when they do meet criteria for autistic disorder, the clinical "gestalt" may not be that which we tend to associate with autism. Some clinicians might not believe that the girl ever had symptoms which could have fitted a diagnosis of "full-blown" autism.

Furthermore, in the older age range – in teenage and adult age – we sometimes meet girls with other presenting problems, such as anorexia nervosa, paranoid disorder or mild paranoid problems, and obsessive compulsive disorders of various kinds, who, on close examination and after having presented a detailed developmental history, appear to have almost the same kind of social impairment as that seen in autism. Many of them also seem to be have similar communication problems. However, these symptoms are milder and have not surfaced to the extent that they have in clear-cut autism early in life. These cases only just fall short of fulfilling criteria for autistic disorder. Some of them actually do fulfill these criteria, but the fact that they present as anorexia nervosa or obsessive-compulsive disorder seems to divert the clinician’s attention from the autism-suspected symptoms. In a recent controlled population-based study of anorexia nervosa, there was a clear increase of autisticlike conditions (Gillberg & Rastam, 1992).

However, even in cases where anorexia nervosa or obsessive compulsive disorder or paranoid disorder can be diagnosed, there is the need to diagnose the comorbid social/communicative impairments. But what label do we use? Clearly, when the criteria for autistic disorder are not met, we cannot make that diagnosis. Also, even diagnoses of pervasive developmental disorder NOS (APA, 1987), atypical autism (WHO, 1987) or autisticlike conditions (Steffenburg & Gillberg, 1986) may seem inappropriate in that the degree of social and communicative impairments is not perceived as extremely severe. Asperger syndrome criteria (Gillberg & Gillberg, 1989) may not be met either, often because of the lack of a particularly obsessive interest.

Nevertheless, the underlying deficiencies in ability to perceive of other people’s perspectives (deficiencies in theory of mind skills (Frith, 1989)) appear to be of a similar quality as those associated with the empathic disorder seen in its most typical form in autism and Asperger syndrome.

The present paper puts forward two hypotheses. The first one is that some crucial aspects of the core deficit in autism (often described as "qualitative impairment in reciprocal social interaction") could be more common in females than previously believed. The second hypothesis is that the reason for underreporting females in the past has been the overreliance on the male prototype of autism (including its sometimes aggressive and domineering qualities) in the delineation of diagnostic criteria for the behavioural phenotype. We discuss these hypotheses in relation to six brief case histories of young girls with severe social impairments.

Case Histories
The following six cases are reported because they (1) were girls, (2) presented with a picture which was clinically difficult to categorize, (3) at one time during development met criteria for autistic disorder.

Case A (10 years) A is the first-born of two unrelated parents. Her younger sister is healthy. Her father suffers from dyslexia and his mother’s brother’s son has been diagnosed as suffering from infantile autism and mental retardation (and is living in an institution). The father’s maternal grandmother has been diagnosed with manic-depressive illness. A’s maternal grandfather had alcoholism. Both parents (low middle class) are employed full-time and have several good friends and many acquaintances. They have been worried about A’s social development ever since she was a baby of a few months’ age. Mother had edema in pregnancy (treated with diuretics). Delivery was normal at term. Birth-weight 2800 g. Head circumference 37 cm (corresponding to more than 2 SD above the norm). Because of macrocephaly she was evaluated at 1 month of age by a child neurologist but was declared "within normal limits." Table 1. Some psychometric and background characteristics in individual cases A B C D E F Age (years)   10 9 8 8 8 6 Number of DSM-III-R criteria met 10 8 8 10 13 11 ABC (Krug et al., 1980) score 40 42 44 58 80 65 social   7 7 17 3 26 13 language 7 17 3 7 13 12 behaviour 7 1 9 19 10 14 sensory   6 3 6 12 19 14 other   13 14 9 17 12 12 CARS (Schopler et al., 1980) score         29 80   WISC-R IQ   61 73 92   84   highest score* PC DSY S   DSY   lowest score* C PA PA   PC   more than 25 IQ points between              highest and lowest score no yes yes   yes   VIQ > PIQ (more than 15 points) no no no   no   PIQ > VIQ (more than 15 points) no no no   no   Overall IQ-level** MMR NA A NA NA A Sally-Anne experiment (Frith, 1989) failed np*** yes np*** yes yes np*** Age (years) first consultation 1 1 1 4 3 4 Age at diagnosis 10 9 8 8 8 6 * PC = Picture completion, PA = Picture arrangement, DSY = Digit symbol, C = Comprehension, S = Similarities ** A = average intelligence (IQ>85), NA = Near average intelligence (IQ70-84), MMR = Mild mental retardation (IQ50-69) *** np = not performed From before age 6 months, the parents felt that she was socially unresponsive in many ways. She had a poor suck and needed much sleep. Gaze contact was "normal" and she seemed to like body contact. She only walked at 21 months. She had difficulties chewing solids. She spoke relatively complicated sentences at age 3 years. At age 9 months she was referred to an orthopedist for a rotated left foot. She received help from a physiotherapist and was followed up by a child neurologist. She was found to have poor balance and motor control. At age 4 years she was evaluated by a psychologist (Griffiths developmental scale II), who found her to be slightly delayed in development except with respect to language and activities of daily life. From age 2-7 years, she would not play with other children. Silently she would observe them, but she could not be prompted to participate. She always wanted to be near other people. She constantly said no to everything. She threw many severe tantrums every day if demands were made. She could not interpret the expression on people’s faces. She would approach strangers and make a number of repetitive demands or question them endlessly. At home she chattered constantly, but in an echolalic fashion. She showed strange reactions, such as starting to cry when given something she had wanted for a long time or when praised. She was attracted to running water and would flap her hands in the shower. She hates loud music and strong noise. Overall she was considered as extremely passive and showed little interest in the environment. She insisted on various routines. She wanted to smell things. Most of these problems still remain, but are slightly less obvious now than they used to be two or three years ago. She started normal school but could not acquire reading and writing skills and was therefore moved to an ESN classroom. It was not until age 10 years that she was referred to a child neuropsychiatrist for evaluation. The results of the psychological and medical work-up are shown in Table I and II. In summary, she meets criteria for autistic disorder and has a fullscale IQ of c 60 (Griffiths and WISC results averaged). On the Autistic Behavior Checklist (Krug et al., 1980) she received a relatively low score of 40. She had a number of minor physical anomalies and an MPA score of 7. She was left-handed (like mother). A CAT-scan of the brain showed agenesis of the corpus callosum (the CAT-scan of the relative with infantile autism was re-examined, but did not show major abnormalities). The EEG showed moderate increase of low-frequency activity (theta- and delta-waves) over both hemispheres. There was a suspicion of amblyopia on the left side. A chromosomal culture showed a 3-6-translocation (both parents have normal chromosomes). The CSF HVA:HMPG quotient was 5.6:1, which is in the high normal range (Gillberg & Svennerholm, 1987) Case B (9 years) B is the first-born child to unrelated parents who separated when B was 5 years old. Her younger brother (7 years) is healthy. The mother, her sister – who is also dyslexic and "odd" – and father all have club-feet. The mother, who works as a secretary lives alone with the two children. Pregnancy was uneventful. Delivery took place after 41 full weeks’ gestation. Birthweight was 3160 g. There were no obvious early developmental or social problems. However, from around age 1 year a tendency to ataxia was noted. She walked unaided at 18 months and was referred to a neuropediatrician around this age because of her overall slow motor development. She was found to have a tendency to club-feet, but EMG and nerve conductance velocity examinations yielded normal results. Mother was also examined, but no cause for her club-feet could be found. Table 2.  Medical background factors in individual cases A B C D E F Autism associated heredity + + + + (+)* + autism + 0 + 0 0 + Asperger syndrome - - + + - - dyslexia + + 0 + 0 + mental retardation + 0 0 + 0 + epilepsy 0 0 0 + 0 0 Major problems in pregnancy 0 0 0 0 + 0 Birthweight (g) 2800 3160 3390 4030 3220 2750 Intrapartal major complications 0 0 0 0 0 0 Minor physical anomaly score (Waldrop & Halverson, 1971) 7 3 0 1 0 0 Syndrome CCA FA? 0 0 0 FRAX CAT-scan major abnormality + 0 0 0 0 0 EEG major abnormality + 0 0 0 0 0 Auditory Brainstem Response abnormal 0 0 0 0 0 0 Chromosomes (cultured in folic acid depleted medium) 3-6T N N N N FX CSF HVA (nmol/l) 277 446 - 447 368 388 5-HIAA 97 185 - 114 121 98 HMPG 49 61 - 44 42 42 * see text! CCA=Corpus callosum agenesis, FA=Friedreich ataxia, FRAX=Fragile X syndrome, 3-6T=Chromosome 3-6 translocation, N=Normal, FX=Fragile X chromosome abnormality B was admitted to a special pre-school for children with motor control problems and received physiotherapy and later speech therapy because of obvious speech-language problems. She was described as hyperactive and attention deficient. She threw severe tantrums and was often perceived as "aloof." She would love to spin herself and to flap her hands. She drooled a lot. Around age 3 years she was again evaluated by the neuropediatrician who found ataxia, muscle weakness of both hands, a convergent squint on the left side and a Babinski sign bilaterally. At age 6 years she had a squint operation. At age 8 years she was examined with a CAT-scan of the brain which yielded normal findings. EEG showed spikes and slow waves bilaterally after sleep deprivation. The CSF HVA:HMPG quotient was 7:1. She was referred to the child neuropsychiatrist by the neuropediatrician at age 9 years because of obvious difficulties in relating and communicating with other people and because of various oddities in her behaviour. She attended a normal classroom but had a full-time special assistant. From early in life, she showed mild gaze avoidance. With mother she showed clinging behaviour and with strangers she showed a lack of reticence and distance. She occasionally "played" with a girl several years younger and with her younger brother with whom she tended to jump up and down on occasion. She could not interpret people’s facial expressions. She had severe language comprehension problems and first spoke only in echolalic phrases. Her speech was at times almost unintelligible because of severe articulation difficulties. She would tiptoe and flap her hands whenever excited. She collected things and kept them in her bed. She was reported to have a fantastic long term memory. Most of these characteristics are still present. The results of the neuropsychiatric work-up are detailed in the tables. In summary, at age 9 years, she only just fulfilled criteria for autistic disorder and showed an intellectual level corresponding to IQ c 70 (WISC and Leiter averaged). She scored 42 on the ABC. She failed the Sally-Anne experiment (Frith, 1989). The speech therapist diagnosed semantic pragmatic disorder. She got a score for minor physical anomalies of 3. She was right-handed, but showed extreme problems in using her left hand. Hypothetically this could indicate that she might have unilateral (right-sided) brain damage affecting the motor skills of the left hand. Alternatively it could be due to severe muscle weakness in combination with lack of training of the left hand. The child neurologist has diagnosed neuromuscular disorder (possibly hereditary) involving club-feet, ataxia and weakness of the hand muscles, but, so far without a name. However, many features of her neuromuscular disorder are compatible with a diagnosis of (atypical) Friedreich ataxia. This disorder is associated with progressive loss of afferent neurons to the cerebellum but less often with clear damage to the cerebellum itself. Brain stem changes are relatively common. Auditory Brainstem Response examination was normal. Case C (8 years) C is the first-born of two children born to unrelated parents who separated when C was 3 years old. Her younger brother is healthy.Her father has remarried and now has another daughter, 2 years of age, who is healthy. Mother and the maternal grandmother were both slow in gross motor development. Grandmother is said to be "odd" as is one of her sons who has extreme and narrow interests. One sister of the maternal grandfather has a daughter who has received a diagnosis of infantile autism. C’s half-sister appears to be strongly left-handed. The mother, who works part-time as a nurse, lives alone with her two children. Pregnancy was reported normal. Birthweight was 3390 g. Delivery was protracted (> 24 hours) and the Apgar score was 9. She was very calm and still as a baby. Gaze patterns appeared to be normal. She walked unaided at 18 months but with considerable clumsiness and unsteadiness. She was observed at the well-baby clinic to have moderate muscular hypotonia. At age 2.5 years she was tested there with the Griffiths developmental scale II and was found to be delayed as regards motor skills and "performance." Her speech was immature, but language competence was judged to be within normal limits. She was then followed at the well-baby clinic and was not referred to the child-neuropsychiatrist until at the age of 7 years when the parents asked to be referred to one of the authors. She had no friends, but would like to participate in games. She did not know "the rules of the game." At the local day-care centre she would stand passively, back turned, staring with an empty gaze into a wall. She was extremely interested in tears in other children’s eyes, but could not understand their implication. She could engage in endless imitation of people talking on the telephone or other persons not involved in direct social interaction. She would look people in the eye, but only very briefly. Almost all these problems still remain. Her language once was extremely echolalic and is now used mostly in incessant questioning. She does not seem to be able to adapt to normal modes of communication and cannot take proper part in turn-taking conversations. She shows hand-waving stereotypies. She has an obsessional interest in perfume and will immediately remember the name of any new perfume. Her "imaginative" play is extremely repetitious (calls up the dentist on her toy telephone again and again). She is pedantic, ritualistic and throws tantrums if routines are broken. She smells and tastes objects. Apart from the routines, she appears to have little will of her own. The neuropsychiatric work-up is summarized in the tables. Briefly, she only just fulfilled criteria for autistic disorder and had normal-low normal intelligence with an IQ of c 90 (WISC, Leiter and Griffiths combined) Her ABC score was 44. The medical investigation was negative, except that the EEG showed slight increase of low-frequency activity. Case D (8 years) D is the third of four children born to healthy, unrelated parents. D’s elder brother has severe dyslexia requiring special education measures. Her maternal aunt has a similar problem in reading and writing. The paternal grandmother is "a loner who has difficulties with social interaction." Her sister’s son has been diagnosed as suffering from Asperger syndrome and generalized tonic-clonic seizures. The parents (working class) both used to be employed, but after the birth of the youngest child, mother has remained at home. There were several viral infections in pregnancy, but none of them very severe. Delivery was normal. Birthweight 4030 g. The Apgar score was 8 at 1 minute and there was a tendency to neonatal irritability. During the first year there were major difficulties in getting her to sleep and she seemed to need little of it. She walked unaided at 11 months and spoke like a normal 2-year-old at the age of 2 years. She had a voracious appetite. From age 2 to 4 years she seemed to develop very slowly and still spoke like a 2-year-old at the age of 4 years. At the age of 4 years she was referred from the well-baby clinic to the local child psychiatric clinic with a suspicion of autism. She was diagnosed as suffering from mental retardation but not autism and was referred to a neuropediatrician. A speech therapist saw her and found her to have abnormal speech and language relative to her developmental level. She also described her as yielding only "fleeting contact." She started school in an ESN classroom. At the age of 7 years she was referred to a child neuropsychiatrist. D was gaze avoidant ever since the age of 2 years, possibly longer. She wanted always to be close to mother or father and mother was not allowed even to be alone in the bathroom. She "played" with an occasional boy, considerably younger, but this was not on her own initiative. She had a strong tendency to treat people as objects and to grab, hug or touch people in an insensitive way. Her speech was deviant with echolalia and jargon. Her prosody was very variable. The speech therapist diagnosed her as having a semantic-pragmatic disorder. These problems remain. Her behaviour has changed over the years. Sleep problems were overwhelming during the first years but are now somewhat less of a problem. However, D is still on alimemazine (a sedative antihistamine). She tends to cry a lot and has a lot of fears including the dishwasher, tractors, the wood, the sight of blood, the shower and hearing various sounds. She imitates other people a lot, but does not understand their facial expressions. She comes up too close to other people. She lines up things. Previously she could not stand any kind of environmental change but this is now slightly less of a major problem. She is an excellent drawer of pictures. She has exceptional rote memory skills. She wrings her hands in a stereotyped fashion. Her great interest in life is the amassing of catalogues and books. The neuropsychiatric work-up is briefly outlined in the tables. She fulfilled criteria for autistic disorder. According to the combined results of various tests, she has an IQ of c 70 (WISC, Leiter and a Swedish test for language comprehension), but, so far she has cooperated poorly in the testing. She got a score of 58 on the ABC and 30 on the CARS – Childhood Autism Rating Scale (Schopler et al., 1980) which indicates "mild autism." She failed the Sally-Anne experiment. The medical investigation yielded normal results except that the CSF HVA:HMPG quotient was 10:1. Case E (8 years) E is the second-born of three daughters to unrelated parents. The mother has received treatment by a psychiatrist for problems which have been difficult to diagnose. She says the father has some "autistic traits", but this has not been corroborated at personal interview with him. Both parents (lowest social class) used to work full time, but recently the mother decided to stay at home with the children and the father started looking for a new job. The family has moved to a strictly rural area to get away from the problems associated with having E among other people. E owns a horse that she takes care of in a very meticulous way. Mother was operated on because of appendicitis in the 5th month of pregnancy. She had premature labour and received hospital treatment in order to stop this. During the last months of pregnancy there was a moderately raised blood pressure and generalized edema. Delivery was uneventful at term. Birthweight was 3220 g. Soon after birth, the mother felt there was