At the Centre for Human Genetics in Leuven, a long tradition exists in research on causes of mental retardation in general. In recent years their has been a growing interest in the field of autism and autistic-like disorders.
All subjects stayed in "De Speling" and "Autigone", two residential grouphomes, especially established for persons with autism or pervasive developmental disorders. At the time of the study, autistic disorder and pervasive developmental disorder was defined according to DSM-III-R criteria (AMA 1987). 16 subjects received the diagnosis of autistic disorder (299.00), the remaining 5 subjects fulfilled the criteria for pervasive developmental disorder not otherwise specified (299.80). The group comprised 21 cases (18 males, 3 females) aged between 16-32 years at the time of medical examination.
Two persons have a normal intelligence, 1 adolescent has a borderline IQ, 3 persons are mild mentally retarded, 12 persons are moderate mentally retarded, and 3 are severe mentally retarded. In our group 18/21 have a mental retardation (85.71%). These results confirm the data in literature, since most authors agree that the figure is somewhere in the range of 65 to 85 per cent.
Important to mention is that the three females are more severely retarded than the men: 2 are moderately retarded, 1 is severely retarded.
In 4 persons, the diagnosis of X-Iinked mental retardation with marfanoid habitus was made. All four patients are young men. Their mental level varied from borderline IQ (1) to mild (2) and moderate (1) mental retardation.
The diagnosis of velo-cardio-facial syndrome or Shprintzen syndrome was made in two patients. Their intellectual level was mild and moderate mental retardation respectively.
One person has Noonan syndrome, one female patient was diagnosed as Cohen syndrome, one person with céroide-lipofuscinose, one person with X-linked adrenoleucodystrophy, one person has a Peters'anomaly with coloboma, one person with Basal Cell Naevi, and in one patient a rare chromosomal translocation was found (46,XY, t(1, 15)).
In 8/21 (38.09%) patients the cause of the autistic(-like) behaviour and mental retardation remains unknown.
Chromosomal aberrations involving almost all the chromosomes of the human karyotype have been reported in singular cases of autism. In this group in one person a translocation between chromosome 1 and chromosome 15. Whether or not these chromosomal aberrations are associated with autistic behavior by chance alone or not remains to be established (Coleman & Gillberg, 1992). Patients with autistic symptoms are reported time to time who are found to have other established syndromes. Gillberg & Coleman (1 992) describes 12 known syndromes which have a subgroup of children/persons with en autistic syndrome: Cornelia de Lange syndrome, Fetal alcohol syndrome, Hypomelanosis of Ito, Joubert syndrome, Lujan-Fryns syndrome, Moebius syndrome (congenital facial diplegia), Neurofibromatosis, Rett syndrome, Sotos syndrome, Gilles de la Tourette syndrome, Tuberous sclerosis, and Williams-Beuren syndrome.
In the studygroup, 4 persons received the diagnosis of Lujan-Fryns syndrome (Lujan et al., 1984; Fryns & Buttiens, 1987). Major phenotypically criteria are: distinct craniofacial dysmorphism such as a long and narrow face, high nasal bridge with long nose, a highly arched palate and maxillar hypoplasia. Most of them are mild to moderate mentally retarded. Behavioural problems, marfanoid habitus with excessive span, longer slender hands and feet and normal adult height, and a hypernasal voice are the remaining major phenotypically criteria. Sporadic cases of mainly males have been reported.
The most constant features of this syndrome are the marfanoid habitus and the mental retardation. Behavioural problems also seem to be a good clinical criterion, present in about 75% of the reported cases (Lacombe, 1993).
The association of X-Linked mental retardation and Marfanoid habitus and autism was firstly described by Gurrieri & Neri (199l). These authors described two individuals with this syndrome as having autism.
In 14 boys and men, aged between 12.10 and 32.7 years, recently diagnosed at the Centre for Human Genetics (Spaepen, Hellemans & Fryns, unpublished data), not only behavioural problems are found but serious disturbances are very common, if not a major feature of this condition. In their studygroup , a 100% rate of psychiatric disturbances was found.
Using the diagnostic criteria of the DSM-III-R, in 4 persons the diagnosis of autistic disorder (299.00) was made, and in 10 the diagnosis of pervasive developmental disorder not otherwise specified (299.80). In this latter group, Spaepen et al. found 4 boys having the multiplex developmental disorder as described by Donald Cohen in 1987 and 1 boy having an Asperger syndrome, two conditions not specified in the DSM-III-R classification. The autistic boys could be subdivided according the types introduced by Lorna Wing in 1979, three categories: 2 aloof autistic boys, 1 active but odd autistic boy and 1 passive autistic boy.
Spaepen et al. concluded that the whole "spectrum" of autistic disorders from Asperger-syndrome with normal intelligence on the one hand and the severely retarded aloof type of autistic disorder on the other hand is found in the group of X-linked mental retardation with marfanoid habitus.
Another important "new" genetic syndrome of which a subgroup of children show autistic or autistic-like behaviour is the velo-cardio-facial (VCFS) or Shprintzen syndrome (1 978). This syndrome is characterized by cleft palate or velopharyngeal insufficiency, cardiac anomalies, typical facial appearance, learning disabilities and/or mental retardation. Inheritance is autosomal dominant with variable expression. The incidence is unknown but somewhere in the range of 1:5000 or 1:3000. The discovery of submicroscopic deletions at 22ql1 has confirmed that VCFS is a specific syndrome (Scmabler et al., 1992).
Learning disabilities have been documented in nearly all patients with VCFS. Mental retardation (mild to moderate) seems to be present in 40%.
Besides the learning problems/mental retardation and the speech-language problems, a typical behaviorprofile and personality type is described: children with VCFS tend to have a bland affect, with little facial expression. Their social interactions with others seems to be deficient in terms of quantity and quality (Golding-Kushner et al., 1985).
Shprintzen and co-workers (1 992) stresses the need for follow-up of patients with VCFS. They observed in at least 1 0% of their patients "schizophrenia-like" symptoms including psychosis which appear to become evident in adolescence or early adulthood.
This study once again stress the need for a thorough medical evaluation of all children and adults with an autistic or autistic-like disorder. And patients where the diagnosis of en X-linked mental retardation with marfenoid habitus or velo-cardio-facial syndrome has been made, need to be referred for a psychiatric evaluation.
University Hospital
Center for Human Genetics
Department of Clinical Genetics
Herestraat 49
B-3000 Leuven
Belgium
De Speling
Schrieksesteenweg 73
2220 Booischot
Belgium