Ring chromosome 13 syndrome in an adult male with mild mental retardation
Takeshi MATSUISHI,1) Anne MILLAR2), Tetsuaki YAMAGUCHI,3) Keiko ENDO3)
1)Yokohama National University, Faculty of
Education and human sciences, Department
of Special Education
2) Yokohama Rehabilitation Centre, Department of Rehabilitation
3) Yokohama City University, School of Medicine, Department of Psychiatry
Name and Address for the correspondence
Name: Dr. Takeshi Matsuishi, Yokohama National University, Faculty of Education and Human Sciences, Department of Special Education
Address: 79-2,Tokiwadai, Hodogayaku, Yokohama City, 240-8501, Japan
A case of ring 13 syndrome in an 18-year-old male is presented with particular focus on mental retardation. The clinical picture was characterised by mild mental retardation, microcephaly, large low set ears, a broad nasal bridge, epicanthus, micrognatia and short philtrum. A review of the literature with a focus on mental retardation concluded that descriptions of mental retardation were often unqualified and at times ambiguous. Furthermore, in contrast to the characteristic description of ring chromosome 13 syndrome which describes marked mental retardation a small number of cases with mild mental retardation exist .
Keyword: chromosomal abnormality, mental retardation, ring chromosome 13 syndrome,
Ring chromosomes show much diversity in their resulting clinical features. It is said that ring 13 exhibits the least clinical variation ( Martin et al. 1982) and a defined syndrome has been gradually emerging since it was first described by Le Jeune et al. in 1968. The present clinical picture is one characterised by marked mental retardation, microcephaly, craniofacial dysmorphia and physical malformations. In this paper we describe a new case of ring chromosome 13 syndrome in an 18-year-old man. As the literature is dominated by detailed accounts of the physical presentation of these cases we focus on mental retardation and present a review of the literature from this viewpoint.
The patient was born at 40 weeks after an uneventful pregnancy to a 21-year-old mother and a nonconsanguious 28-year-old father. Both parents are healthy. The delivery was complicated by looping of the umbilical cord around the probands neck causing slight asphyxia. Birth weight was 2640 g, length was 47 cm and head circumferance was 30 cm. The patient is the eldest of 3 siblings all of whom are physically and mentally normal.
Past medical history reveals mentaland physical developmental delay. Acquisition of motor milestones was retarded. First steps were taken at one year and 6 months and first words at two years 6 months.At age 10, in 4th grade of elementary school, he was transferred from a mainstream class to a special class for mild mental retardation within the same school. After graduating junior high school he was then placed in a special school from which he graduated at age 18. At that time he was referred for psychological evaluation where he scored 50 on the Tanaka-Binet IQ test, thus classifying him as mildly mentally retarded. From there he was placed in a job in a bakery.
On examination at age 18 the patient presented with microcephaly and facial dysmorphia including large low set ears, a broad nasal bridge, epicantus, micrognatia and a short philtrum (fig.1)*.Height was 165 cm, weight 43 kg and head circumferance 52 cm.Neurological examination was unremarkable.
Chromosomal analysis performed on 30 peripheral blood lymphocyte by the G-Banding technique revealed ring chromosome 13 in all 30 cells.By high- resolution G-Banding the breakpoints were identified (Fig 2)*. We can describe the karyotype thus: 46,XY,r(13)(p11q34).
The patient presented as a very sociable and cheerful young man. His verbal intelligence was high and he possessed good language skills. He could describe his hobbies and interests fluently. He is independent in all activities of daily living and in the use of public transport. Both in his home life and working life he has many responsibilities. At home he takes care of the dog and does shopping errands. At the bakery he is responsible for collecting and distributing bread to designated areas.
*Fig 1 & 2 are available on request of a reprint.
A number of investigators have indicated that ring chromosome 13 syndrome exists as a clinical entity or entities (Nieburh & Ottosen 1973; Martin et al. 1982; Parzchela et al. 1985) . Nieburh & Ottosen (1973) suggested three possible distinct clinical syndromes involving chromosome ring 13 based on the variable loss of genetic material from the long arm of chromosome 13 during ring formation : group I, with loss of segments 13q34 and possibly 13q33, is associated with severe mental retardation, microcephaly with true hypertelorism, salient frontal bossing erasing the nasal bridge, forward-slanting maxillary incisors, and large ears with deep sulci helici;group II,with a loss of the segment 13q32 and part of 13q31, is associated with the clinical features of group I plus aplasia or hypoplasisa of the thumbs, foot or toe abnormalities, severe genital malformation, anal atresia, and eye malformations; group III, with a breakpoint at 13q21 is characterized by retinoblastoma. Based on this classification our case would appear to belong to group I. While some clinical features specific to this group were observed , such as microcephaly and large ears, the extent of facial dysmorphia and mental retardation were significantly slighter. The existence of such a distinct pattern based on breakpoints is thought to be unlikely by some authors ( Steinbach et al. 1981; Hoo et al. 1984; Brandt et al. 1992).
Following a review of the previously reported 21 cases with identified breakpoints it appears that the main focus is on physical presentation and the existence or not of a clinical syndrome based on breakpoints. While severe mental retardation is cited as a characteristic feature of ring chromosome 13 syndrome (Rethoré & Pinet 1987) little quantitative or qualitative descriptions regarding mental development could be found. It is this aspect of ring chromosome 13 syndrome that we wish to focus our attention on in this paper. In a review of the above mentioned 21 cases 2 were still born (Stetten et al 1990; Brandt et al. 1992 ), one of which was anencephalic (Brandt et al. 1992), 10 were described as severely mentally retarded (Mikkelsen & Niebuhr 1969; Fryns et al. 1974; Magenis et al. 1976; Cossu et al. 1979; Lagergren et al. 1980; Jones et al. 1981; Steinbach et al. 1981; Martin et al. 1982), 6 were described non-specifically as mentally retarded (Niebuhr & Ottosen 1973; Hoo et al. 1974; Noel et al. 1976; Steinbach et al. 1981; Martin et al. 1982; Parcheta et al. 1985) and 3 were described as mild to moderately mentally retarded(Verma et al. 1978; Hernandez et al. 1979; McCorquodale et al. 1989). A correlation between the degree of mental retardation and breakpoint could not be identified . However all mild and moderate cases including this case have a breakpoint at q34.
With regard to the present case we conclude our patient to be mildly mentally retarded. Hernandez et al.(1979) describe a girl of 9 years with mildly delayed psychomotor retardation and an IQ of 60. The case described by McCorquole et al. (1989) of a 5 year old boy is moderately mentally retarded. Finally the case of a 2 years and 8 month old girl presented by Verma et al.(1978) appears to be mildly mentally retarded.
While it is evident that the majority of the reported cases fall into the severely mentally retarded category it is not the 100% as described by Brandt et al.(1992) who reviewed almost the same cases. Indeed contrary to the classic profile of ring chromosome 13 syndrome (Rethoré & Pinet 1987), we would like to emphasis mild and moderate levels of mental retardation exist in ring chromosome 13 syndrome patients.
Up to now little attention has been paid to the mental and psychomotor development in patients with ring syndrome 13 syndrome. Further detailed and accurate descriptions of mental development are urgently needed in order to extend the knowledge on their long term mental prognosis.
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(Journal of the Yokohama National University, The Educational Sciences Vol.37:229-234, November, 1997)