Neurological Complications of the Ring(22) Syndrome: A Case Report Norio Sakuragawa, MD, Kimiko Adachi, MD, Mari Hayashi, MD, and Nobuyoshi Fukuhara,
The first Japanese case of the ring (22) syndrome was described. The patient had diffuse neurological involvement of the central, peripheral nerves and muscles in addition to the phenotypical characteristics of this syndrome. Sakuragawa N, Adachi K, Hayashi M, Fukuhara N: Neurological complications of the ring (22) syndrome: A case report. Brain Dev 2: 91-96, 1979
Reisman et al [10] and Welber et al [17] have each reported one child with a deleted G chromosome who showed a distinctly different clinical phenotype from that of "antimongolism." Warren et al [15. 16] proposed that these syndromes should be referred to as "G deletion syndrome I (antimongolism)" with a deleted or ring No 21 and" G deletion syndrome II" with a deleted or ring No 22 chromosome. The clinical characteristics of G deletion syndrome II, which were summarized by Warren et al [15] include mental retardation, microcephaly, high-arched palate, large or lowset ears, hypotonia epicanthal folds, syndactyly of toes, ptosis, bifida uvula and clinodactyly. Magenis et al [3] and Crandall et al [2] succeeded in identification of 22 r chromosome by quinacrine fluorescence [1]. Rethore [7] described 14 cases in his series of this syndrome which were subjected to chromosome investigaFrom the Departments of Neurology, Brain Research Institute (NS, MH, NF), and Hygiene (KA), Niigata University, Niigata. Received for pUblication: December 29, 1978. Accepted for pUblication: May 14, 1979.
Key words: Chromosome aberration, ring (22) syn· drome, neurological complication. Correspondence- address: Dr. Norio Sakuragawa, Division of Child Neurology, National Center for Nervous, Mental and Muscular Disorders, 2620, Ogawa-Higashimachi, Kodaira, Tokyo 187, Japan.
tion by the G or R banding technique. We report the first Japanese case of the (22) syndrome, with special attentin to the neurological complications, who suffered from diffuse involvement in both the central and peripheral nervous systems in addition to the characteristic findings of muscle biopsy. Case Report The patient is an 8-year-old boy who was the product of a normal pregnancy with a slight weak fetal movement. He was born ,to non consanguineous and healthy mother, aged 21 and father, aged 29. There are no other siblings. Labor was induced by medications 10 days prior to the due date because of slight spotting. Delivery was complicated by breech presentation, forceps extraction and umbilical coiling which led to slight asphyxia at birth. Birth weight was 2,150 g. He had to have nasal feeding for the first week of life because of poor sucking. The neonatal period was unremarkable except for a high fever (39.0°C) on the 4th day without any detectable causes. The acquisition of milestones was retarded; head control at 6 months, sitting without support at 10 months, smile at one year, standing with support at 5 years and jargon at 6 years old. At the age of 7 years, he developed a generalized convulsion and has been treated with anticonvulsants with
Chromosome studies were carried out by lymphocyte culture on two occasions. occasions. Karyotypic analysis of all 25 cells revealed 46, XY, G(r), which was confirmed by G staining [1] (Figs 6 and 7). The karyotype of his mother was 46 XX. His blood type is the same as that of his mother which is type a 0 and D (+). Discussion
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Phenotypical characteristics of the ring G syndromes were summarized by Warren et al f151 from 4 described cases. In 1975, Veall et al [14] questioned the justification of the clinical entity of the ring 22 chromosome syndrome because of the great variability. Also Rethore [9] in 1975 commented that the ring G syndromes appear to be less well defined than other syndromes due to autosomal aberrations. Both Veall et al and Rethore, however, suggested that more patients should be described and studied by a banding technique for further evaluation of this ring (22) syndrome. Our paFig 3 Computer tomography demonstrating the dilated lateral ventricles and cortical atrophy. Fig 4 EEG showing a single spike or spike and wave complex in the bilateral frontal areas. Indicator for a second and 50 m V.
Fig 5 Light microscopy of the left quadriceps femoris demonstrating the prominence of type I fibers and type I fiber grouping in the left upper part. Arrows indicate type II fibers. ATPase at pH 4.2, x 120.
Sakuragawa, et al: The r (22) syndrome
93
Table 1 Analysis of dermatoglyphics 1
2
3
4
5
Finger pattern
R L
U W(DL)
W
u
u
W
W W
W W
Toe pattern
R L
W(DL) W(DL)
W W
W W
W(DL) W
F F
Axial triradius
Rt Lt
14.4% 11.7%
Max atd angle
R L
38° (t) 42° (t)
Hypothenar area
R L
4th
Simian crease
In terdigi tal area Digital triradius
AU (arch ulnar) AU
R (-) L (-)
R L
Thenar
2nd
3rd
0 0
0 0
0
0
L
a ,b, c, d
tient had the phenotypical characteristics described by Warren et al. Schindler et al [12] analysed the dermatoglyphics in the G deletion syndrome, which are characterized by distally placed triradii, a high incidence of hypothenar patterns and total absence of the C triradius or its movement to a third interdigital. position in addition to the significant increase in whorls and decrease in both ulnar and radial loops. Our patients showed the excess of whorls and hypothenar pattern with normal axial triradius and C triradii. We collected 29 cases from the published reports which include the series of Rethore [9], Veall et al [14] and others. As shown in Table 2, frequent neurological complications in this syndrome are mental retardation, delayed motor development, hypotonia, convulsion or EEG abnormalities. There are so far a few reports on neurological evaluation of this syndrome. Epilepsy or abpormal EEG was associated in a few cases. This report might be the first demonstration of cortical atrophy and moderate ventricular dilatation by computer tomography. Delayed nerve conduction velocity has not been reported while the case described by Dubowitz et al [4] showed the normal ranges of nerve conduction velocity. Gait disturbance is usually associated with 94
L
Brain & Development, Vall, No 2, 1979
hypotonia. But hypertonia was described in the cases of Hoefnagel et al [7] ,Richards et al [11] and Rethore et al [9] . Dubowitz described a 10 and 1/2 year-old-boy with ataxic gait. There are so far no other reported case with such associated diffuse atrophy as that in our patient. The study of muscle biopsy performed only in our patient, revealed the grouping of type I fibers without muscle atrophy or cell infJltration. Curless et al [3] described the histological patterns of muscle in 23 hypotonic infants. Eighteen cases showed strong evidence of cerebral dysfunction, consisting of psychological delay, mental retardation and microcephaly. Ten of them had predominance of type I fibers. Chromosome studies were not carried out in these cases. Tanimura et al [13] reported type I predominance in the Down syndrome and suggested the central nervous system abnormalities might be responsible somewhat for the muscle hypotonia. Dunn et al [5] reported a boy with a benign form of con$enital hypotonia with Group 21-22+Y. Muscle biopsy showed normal cross-striation and nerve fibers. Nerve conduction velocity was low in ~e normal range for the age of the child acoording to their own experience. These systemic involvements of the nervous system in our patient with the ring (22) syndrome cannot be explained only by the mod-
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Fig 7 Partial karyotype showing a ring (22) chromosome (arrow).
erate perinatal insults. Type I fiver grouping in biopsied muscle might be one of the associated findings, probably nonspecifically but further information should be obtained from more patients described with special attention in this field.
Acknowledgments We would like to thank Drs. M. Arima and M. Nauuka (National Center of Research for Nervous, Mental and Muscular Disorders) for their help with this publication.
Table 2 Neurological complications of the ring (22) syndrome (No of cases affected/No of cases in our series described) Present case
Mental retardation
20/21
+
Microcephaly
4/14
Hypotonia
6/10
+ +
Hypertonia with increased DTR
3/10
Convulsive disorders (or EEG abnormalities)
4/ 5
+
Gait disturbance (or delayed motor development)
7/ 7
+ +
Muscle atrophy or weakness
1/ 3
Ptosis
2/12
Occult spina bifida
1/ 1
References 1. Caspersson T, Zech L, Johansson C, et al: Identification of human chromosomes by DNA-binding (Bere) 30: 215fluorescent agents. Chromosoma (8ere) 227, 1970. 2. Crandall BF, Weber F, Muller HM, et al: Identification of 21r and 22r chromosomes by quinacrine fluorescence. Clin Genet 3: 264-270, 1972. 3. Curless RG, Nelson MB, Brimmer F: Histological patterns of muscle in infants with developmental brain abnormalities. Dev Med Child Neurol 20: 20 : Sakuragawa, et al: The r (22) syndrome
95
159-166, 1978. 4. Dubowitz V, Cooke P, Colver D, et al: Mental retardation, unusual facies and abnormal nails associated with group G ring chromosomes. J Med Genet 8: 195-201,1971. 5. Dunn HG, Ford DK, Auersperg N, et al: Benign congenital hypotonia with chromosomal anomaly. Pediatrics 50: 578-591, 1961. 6. Fukuyama T, Kawazura M, Haruna H: A peculiar form of congenital progressive muscular dystrophy. Paediatr Univ Tokyo 4: 5-8, 1960. 7. Hoefnagel D, Schroeder TM, Benirschese K: A child with a group-G ring chromosome. Hum Genet 4: 52-58, 1967. 8. Magenis RE, Armendares S, Hexht F, et al: Identification by fluorescence of two G rings: (46, XY,21r) G deletion syndrome I and (46,XX,22r) G deletion syndrome II. Ann Genet 15: 265-266. 1972. 9. Rethore MO, Noel B, Couturier J, et al: The r (22) syndrome. Report of four new cases. Ann Genet 19: 111-117, 1976. 10. Reisman LE, Darnell A, Murphy JW, et al: A child with partial deletion of a G group auto-
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Brain & Development, Vol 1, No 2, 1979
some. Am J Dis Child 114: 336-339, 1967. 11. Richard BW, Rundle AT, Hatton WM, et al: Ggroup ring chromosome in a mentally subnormal girl. JMentDefic Res 15: 61-72, 1971. 12. Schindler JD, Warren RJ: Dermatoglyphics in the G deletion syndromes. J Ment Defic Res 17: 149156, 1973. 13. Tanimura R, Suzuki H, Hara M, et al: Muscle pathology of Down's syndrome; Histochemical and electron microscopic examination of biopsied muscle. Brain Dev (Tokyo) 6: 15-20, 1975. 14. Veall RM, Rundle RC, Chitham RC, et al: A profoundly mentally handicapped woman with a ring chromosome 22. J Ment Defic Res 19: 225243, 1975. 15. Warren RJ, Rimoin DL: The G deletion syndromes. J Pediatr 77: 658-663, 1970. 16. Warren RJ, Rimoin DL, Summit RL: Identification by fluorescent microscopy of the abnormal chromosomes associated with G deletion syndromes. Am J Hum Genet 25: 77-81, 1973. 17. Welber RG, Hecht E, Giblett ER: Ring G chromosome, a new G deletion syndrome. Am J Dis Child 115: 489494, 1968.