Case reports

mucopolysaccharidosis. However, since this com-bination has been described in the literature andsince no other primary cause has been found toexplain the hydrocephalus, a causal relation betweenthe two is plausible. It is also important to recognizethat communicating hydrocephalus may be acontributing factor in mental retardation (Tew andLaurence, 1975). This may be particularly relevant inMPS II which is known to manifest itself with andwithout mental retardation (McKusick, 1972;Yatziv et al., 1977). As a result, when hydrocephalusis present it may be difficult to determine in a givencase whether the mental deterioration is primarilythe result of storage in the central nervous system orof the accompanying hydrocephalus or of both. Inour case, the insertion of a ventriculoperitonealshunt apparently resulted in improvement of motorperformance, but it is still too early to assess thepatient's mental status adequately.

The authors wish to thank Dr Stephen L. Kaufmanfor referring this case to us. His alertness to thepossibility of a storage disorder, despite the paucityof objective physical findings, made possible thediagnosis of MPS II and the proper counselling forthis disorder.

SHAUL YATZIV2 AND CHARLES J. EPSTEINDepartment ofPediatrics,University of California,

San Francisco, California, USA.

References

Fowler, G. W., Sukoff, M., Hamilton, A., and Williams, J. P.(1975). Communicating hydrocephalus in children withgenetic inborn errors of metabolism. Child's Brain, 1,251-254.

McKusick, V. A. (1972). The Mucopolysaccharidoses. Herit-able Disorders of Connective Tissue, 4th ed., pp. 521-686.Mosby, St. Louis.

Neufeld, E. F., and Cantz, M. J. (1971). Corrective factors forinborn errors ofmucopolysaccharide metabolism. Annals ofthe New York Academy of Sciences, 179, 580-587.

Neufeld, E. F., Lim, T. W., and Shapiro, L. J. (1975). Inheriteddisorders of lysosomal metabolism. Annual Review ofBiochemistry, 44, 357-376.

Svejcar, J., and Robertson, W. Van B. (1967). Micro separa-tion and determination of mammalian acidic glycosamino-glycans (mucopolysaccharides). Analytical Biochemistry,18,333-350.

Tew, B., and Laurence, K. M. (1975). The effect of hydro-cephalus on intelligence, visual perception, and schoolattainment. Developmental Medicine and Child Neurology,35, Suppl., 129-134.

Yatziv, S., Erickson, R. P., and Epstein, C. J. (1977). Mildand severe Hunter syndrome (MPS II) within the same sib-ships. Clinical Genetics, 11,319-326.

Requests for reprints to Professor Charles J. Epstein,Department of Pediatrics, School of Medicine,University of California, San Francisco, California94143, USA.

447

Supernumerary small ringchromosome'

SUMMARY A supernumerary small ring chromo-some was found in 30% of cultured peripheralleucocytes and 50% of skin fibroblasts in a 6-year-old boy with mild mental retardation andmidline cleft palate. The extra chromosomeappeared to carry a densely staining region onGiemsa banding. The banding patterns of theremaining 46 chromosomes were normal. Cbanding indicated that the ring chromosomecontained mainly centromeric constitutive hetero-chromatin.Chromosome analysis of both parents showed

normal karyotypes by both conventional andbanding techniques; thus the origin of the ringchromosome could not be determined.

Supernumerary small chromosomes have occasion-ally been reported, appearing mainly as meta-centric (Borgaonkar et al., 1971; Abbo and Zell-weger, 1970; Froland et al., 1963; Gamstorp et al.,1966), or acrocentric chromosomes (Latta and Hoo,1974). Some of the cases were associated with con-genital malformations and others with normalphenotypes (Ellis et al., 1962; Nielsen and Ras-mussen, 1975).

Mosaicism for an extra small ring chromosome(46,XY/47,XY,+r), was reported in a 10-year-oldboy with cheilo-palato-gnathoschisis and mentalretardation (Hoo et al., 1974). We report anotherpatient with mild retardation, midline cleft palate,and mosaicism of 46,XY/47,XY,+r). The similarityof the clinical findings to the previously reportedpatient is of interest.

Case report

This patient (100468) was born at term after a normalpregnancy to a 24-year-old mother and a 31-year-oldfather. The mother had been treated with iodine for a'goitre' until about 2 years before this conception.She was on no treatment before and during thepregnancy. The baby weighed 3400 g at birth andwas considered as a normal newborn except for themidline cleft palate. The mother first became con-cerned about the child's development at 9 months ofage when she noted that he had a big head andgeneralized hypotonia. He could not distinguish herfrom other people. He began sitting at 1l years,

iThis work was supported by Grants GM-19443, HD-02552 from theU.S.P.H.S. and from the National Foundation (C-155).

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walking at 2- years, and did not talk until the age of4, when the cleft palate was repaired. Thyroid studiesperformed at that time were normal.At 6 years of age the physical examination showed

a hyperactive boy. Height was 109 cm, weight 20 5kg (3rd centile), and head circumference 51 cm(50th centile for age). His skin was dry. There was arepaired midline cleft palate, an umbilical hernia,and his left testicle was not palpable in the scrotum oringuinal region. His fingers were short and tapering.The rest of the physical examination was not re-markable. Dermatoglyphs were also within normallimits.

Cytogenetic studies

Chromosome analysis was performed on culturedleucocytes and skin fibroblasts. The peripheralleucocytes showed a mosaicism of 46,XY/47,XY,+r, with 30% of the 50 cells examined showing anextra small ring chromosome (Fig. 1). The cultured

Case reports

skin fibroblasts disclosed the same type of mosaicismwith 50% of 50 cells showing 47,XX,+r. The extrachromosome had a ring shape by conventional Q-banding (Breg, 1972) (Fig. 2) and G-banding techni-ques (Hirschhorn et al., 1973). With G-banding, adensely staining region was seen in this ring chromo-some (Fig. 3). The G-banding as well as Q-bandingpatterns of the remaining 46 chromosomes werecompletely normal. The C banding (Salamanca andArmendares, 1974) showed that the ring chromo-some consisted mainly of centromeric constitutiveheterochromatin (Fig. 4).

Peripheral leucocyte cultures of both parentsrevealed a normal chromosomal constitution byboth conventional and G-banding techniques.

Discussion

Similar clinical findings associated with mosaicismfor an extra small ring chromosome in 2 patientsraises the possibility that the ring chromosome is

Fig. 1 Cell in mitosis, showing the small extra chromosome.

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Fig. 2 Quinacrine fluorescence banding karyotype showing ring configuration.

identical in origin. However this origin was notidentifiable in either of these cases of unbalancedautosomal aberrrationAutosomal ring formation was discussed in detail

by Hecht (1969) and later by Hecht and Vlietinck(1973). Their basic question dealt with the possibilityof correlation of consistent clinical syndromes with

21 22 Y r

Fig. 3 Partial karyotype ofG group and extra ringchromosomes in Giemsa-trypsin banding.

ring chromosomes. The prediction was made thateach patient with a ring derived from a particularautosome might show a different phenotype. Theyexplain phenotypic variability by: (a) location andlength of deletion; (b) number of cell lines found, orthe formation of mosaicism because of the tendencyof ring chromosomes to missegregate; and (c)similar looking rings that originate from differentchromosomes. It may be even more complex to ex-plain a supernumerary mosaic ring chromosome, theorigin ofwhich is unknown. Extra small ring chromo-somes can be considered partial trisomies, with theclinical features depending on the chromosome oforigin. The clinical features of our patient and the onereported by Hoo et al. (1974) include mental re-tardation and cleft palate. This combination has beenfound in patients with complete trisomies 13 (Smith,1976) or 22 (Hsu et al., 1971), or partial trisomies oflq (Norwood and Hoehn, 1974), 7q (Alfi et al., 1973)or lp (Sanchez et al., 1974), as well as the syndromeof partial deletion of 4p- (Hirschhorn et al., 1975).

449

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9

c.A..L.

* \ tv,~~~~~b.ik ~ ~~~~~4

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Fig. 4 C banding showing that the extra ring is mainly centromeric heterochromatin.

It is, therefore, likely that rings formed from segmentsof these chromosomes would result in some similarclinical findings. Such similarity offindings in patientswith ring chromosomes may therefore be the result ofa combination of abnormalities common to twodifferent trisomies or to ring formation from the samechromosomes.

We wish to thank Mrs S. Paciuc and Mrs S. Cristianfor their excellent technical assistance.

S. KAFFE, H. J. KIM, L. Y. F. Hsu,C. B. BRILL, AND K. HIRSCHHORNThe Division ofMedical Genetics,

Department ofPediatrics, Mount Sinai SchoolofMedicine, Fifth Avenue and 100th Street,

New York, New York 10029, U.S.A.

References

Abbo, G., and Zellweger, H. (1970). The syndrome of themetacentric microchromosome. Helvetica Paediatrica Acta,25, 83-94.

Alfi, 0. S., Donnell, G. N., and Kramer, S. L. (1973). Partialtrisomy of the long arm of chromosome 7. Journal ofMedical Genetics, 10, 187.

Borgaonkar, D. S., Schimke, R. N., and Thomas, G. H. (1971).Report of 5 unrelated patients with a small, metacentric,extrachromosome or fragment. Journal de GenetiqueHumaine, 19, 207-222.

Breg, E. R. (1972). Quinacrine fluorescence for identifyingmetaphase chromosomes, with special reference tophotomicrography. Stain Technology, 47, 87-93.

Ellis, J. R., Marshall, R., and Penrose, L. S. (1962). An aber-rant small acrocentric chromosome. Annals of HumanGenetics, 26, 77-83.

Froland, A., Holst, G., and Terslev, E. (1963). Multipleanomalies associated with an extra small autosome.Cytogenetics, 2, 99-106.

Gamstorp, I., Hakensson, L., and Lagergren, J. (1966). Acase of mental retardation with an additional small meta-centric chromosome. Hereditas, 55, 266-277.

Hecht, F. (1969). Ring 4 chromosome: ring autosomes,Lorelei of clinical karyotype correlation and deletion map-ping. Birth Defects, Original Article Series V, 106-113.

Hecht, F., and Vlietinck, R. F. (1973). Autosomal rings andvariable phenotypes. Humangenetik, 17, 99-100.

Hirschhorn, K., Cooper, H. L., and Firschein, I. L. (1965).Deletion of short arms of chromosome 4-5 in a child withdefects of midline fusion. Humangenetik, 1, 479-482.

Hirschhorn, K., Lucas, M., and Wallace, I. (1973). Preciseidentification of various chromosomal abnormalities.Annals ofHuman Genetics, 36, 375-379.

Hoo, J. J., Forster, C., Kinderman, I., Zabel, B., and Hansen,S. (1974). Supernumerary small ring chromosome. Human-genetik, 25, 17-28.

Hsu, L. Y. F., Shapiro, L. R., Gertner, M., Lieber, E., and

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Hirschhorn, K. (1971). Trisomy 22: a clinical entity.Journal ofPediatrics, 79, 12-19.

Latta, E., and Hoo, J. J. (1974). Trisomy of the short arm ofchromosome 17. Humangenetik, 23, 213-217.

Nielsen, J., and Rasmussen, K. (1975). Extra marker chromo-some in newborn children. Hereditas, 81, 221-224.

Norwood, T. H., and Hoehn, H. (1974). Trisomy of the longarm of human chromosome 1. Humangenetik, 25, 79-82.

Salamanca, F., and Armendares, S. (1974). C bands in humanmetaphase chromosomes treated by barium hydroxide.Annales de Genetique, 17, 135.

Sanchez, O., Yunis, J. J., and Escobar, J. I. (1974). Partialtrisomy 11 in a child resulting from a complex maternalrearrangement of chromosomes 11, 12, 13. Humangenetik,22, 59.

Smith, D. W. (1976). Recognizable Patterns of Human Mal-formation. pp. 12-15. Saunders, New York.

Requests for reprints to Dr S. Kaffe, Division ofMedical Genetics, Department of Pediatrics, MountSinai School of Medicine, Fifth Avenue and 100thStreet, New York, N.Y. 10029, U.S.A.

Ring chromosome 8 in a boy withmultiple congenital abnormalitiesand mental retardation

SUMMARY A ring chromosome 8 was found inperipheral blood cells in a boy, whose chromo-somes wer,e studied because of multiple con-genital anomalies. ExaminationN of skin cellsrevealed a 46,XY/46,XY,8r pattern. Applicationof several banding techniques suggested aduplication of the most distal bands of both armsin the ring. The terminal end of 8q appeared tohave been retained as could be shown by R-banding.The anaesthesia and surgery the mother under-

went in the first month of her pregnancy is con-sidered as a possible cause of the chromosomeabnormality.

Ring chromosomes derived from unidentified Cchromosomes have been reported in several cases.

After the development of the banding techniquesthe possibility of identifying the origin of C ringchromosomes led to the publication of reports of 4patients with a ring chromosome 6 (Moore et al.,1973; Van den Berghe et al., 1974; Fried et al., 1975;Wurster-Hill and Hoefnagel, 1975), 2 patients with a

451

ring chromosome 7 (Zackai and Breg 1973), 1 patientwith a ring chromosome 8 (Pfeiffer and Lenard,1973), and 5 patients with a ring chromosome 9(Kistenmacher and Punnett, 1970; Jacobsen et al.,1973; Fraisse et al., 1974; Zdansky et al., 1975;Nakajima et al., 1976). In the case of Kistenmacherand Punnett the identification was based on mor-phology and study of the exchange pattern inducedby mitomicin C.

In this paper a ring chromosome 8 is described in apatient who was studied because of multiple con-genital abnormalities.

Case report

The propositus (born 13 October 1967) is the first oftwo children. At birth his mother was 25 and hisfather was 28 years old. There were no abortions orstillbirths. Unaware of her pregnancy the motherunderwent an appendectomy on account of chronicappendicitis on the 18th day of her last menstrualcycle (premedication: 0-5 mg atropine, 25 mgpromethazine, 20 mg pantopon; narcotics: thiopen-thone-sodium, suxamethonium-chloride, nitrousoxide, and fluothane).

Gestation was uneventful and ended 13 days afterterm. Birthweight was 2770 g, length 47 cm. Feedingwas very difficult in the neonatal period.At 14 years of age the boy suffered from feverish

convulsions. When he was 2 years old he was operatedon for bilateral hernia inguinalis. Because of an im-pending dislocation of the right hip, he was treatedwith a stretch bandage at the age of 24 years. Hesuffered from recurrent infections of the upper res-piratory tract. Psychomotor development was veryretarded.At the age of 5 5/12 years the boy was admitted to

our institution. Physical examination at that timedisclosed the following (Fig. IA and B): dwarfism,dolichocephaly, prominent occiput, asymmetry ofthe viscero-cranium, bilateral strabismus conver-gens alternans, bilateral epicanthic folds, asym-metric ears, tight upper lip, thin lips, gothic palate,asymmetry of the upper dental arch, micrognathia,pectus excavatum, scapulae alatae, wide-spacedareolae mammae, long thorax, bilateral inguinalscars from herniotomy, sacral dimples, and dimplesdorsal of the elbows, camptodactyly of both fifthfingers, hypotonia, and cutis marmorata.The electroencephalogram was normal. Opthal-

mological examination revealed a distinct bilateralhypermetropia and minor astigmatism of the righteye, which seems to be affected by amblyopia.

X-ray examination revealed that the right caputfemoralis was located laterally in the acetabulumand that the right femur was adducted, the right side

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