Case reports

Jrournal of Medical Genetics (1975). 12, 99-113,

Deletion of the short arm ofchromosome No. 10*

Summary. A newborn male infant,whose karyotype was 46,XY,del(10) (p13)is presented. The clinical features in-cluded cleft lip and palate, preauricularpits, low set malpositioned auricles, anti-mongoloid slant ofthe eyes, microcephaly,micrognathia, congenital heart disease,hypertrophic pyloric stenosis, cryptor-chidism, and abnormal dermatoglyphics.The child died at the age of 3 months inoverwhelming urinary infection withsepticemic complications. It is sug-gested that the features described heremay represent a new, clinically recogniz-able chromosomal syndrome.

Characteristic phenotypes have been consistentlyobserved in association with specific numerical orstructural chromosomal alterations. The latterhave been reported in the B group; for instance, thecri-du-chat syndrome resulting from partial dele-tion of the short arm of chromosome No. 5 (Lejeuneet al, 1963; German et al, 1964) and Wolf's syn-drome in partial deletion ofthe short arm ofchromo-some No. 4 (Wolf et al, 1965; Ledo et al, 1967).Similarly, deletions ofthe long arms ofchromosomes18 (de Grouchy et al, 1964) and 21 (Lejeune et al,1964) have been associated with specific clinicalfeatures.

Structural abnormalities of the C-group chromo-somes, however, have hitherto been only rarelylinked to specific identifiable patterns of malforma-tions. This has been variously interpreted to indi-cate inviability of conceptuses in whom theseanomalies occur (Hamerton, 1971). Alternatively,the difficulties encountered in identification of indi-vidual C-group chromosomes before the advent of

banding techniques, may have hindered the estab-lishment of associations between clinically recog-nizable syndromes and the specific chromosomalstructural alterations.

Nevertheless, de Grouchy et al (1968) reported ona case of suspected Cp - chromosomal aberrationwith prematurity and multiple congenital abnor-malities including large, low set ears with pre-auricular tubercles, retrognathia, hypospadias, ingui-nal testes and herniae, abnormal dermatoglyphics,short stature, and developmental retardation. Theexact identification of the chromosome involved wasnot, however, possible. Further, Biscatti (1965)reported a mentally retarded 3-year-old girl withlow set ears, simian creases, clinodactyly, and hyper-telorism. One of her C-group chromosomes wasmissing and replaced by a small metacentric chro-mosome similar in size to members of the E group.A deletion ofthe long arm of a C-group chromosomewas therefore suggested. A more complex re-arrangement cannot, however, be ruled out. Asneither of her parents was cytogenetically studied,the origin of the chromosomal anomaly was notascertained.With the precision now available for identifying

unambiguously individual chromosomes or partsthereof, more of these associations are coming tolight (Alfi et al, 1973; Shokeir, Ying, and Pabello,1973).

In this communication we report a male infantwith multiple congenital anomalies whose karyo-type disclosed partial deletion of the short arm ofchromosome No. 10.

III2 3 4 5 6 7 8 9

IVL: Hoemophilia

2 Chromosomal oberration,lOp- /

I[.Multiple congenitol malformations

FIG. 1. Pedigree.

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Received 12 June 1974.* Supported by the Medical Research Council of Canada.

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Case reportThe propositus (IV.2, Fig. 1), a male infant was bom

on 20 June 1973 to healthy young parents (III.7 andIII.8), both aged 22 years. He was the second in thesibship with an older brother (IV.1), aged 3 who is nor-mal and healthy. Exploration of the family historyrevealed only a haemophiliac paternal patrilineal cousinof the propositus' father. The mother, however, had aprevious spontaneous miscarriage at 10 weeks of gesta-tion some 18 months before her pregnancy with the pro-positus. The pregnancy was marred by pre-eclamptictoxaemia and urinary infections but ended at term in aminimally assisted delivery.At birth he weighed 2530 g and had an apgar of3 and 6

at 1 min and 5 min, respectively. A unilateral completeleft cleft lip and palate anomaly was evident. Because offeeding difficulties and the prospect of surgical repair ofthe lip, he was transferred to the Children's Centre inWinnipeg. The infant was seen in consultation and hewas noted to have, in addition to the obvious cleft lip andpalate (Fig. 2), widely open anterior and posterior fonta-nelles and metopic suture, antimongoloid slant to thepalpebral fissures, bilateral preauricular sinuses, microg-nathia, abnormal dermatoglyphics with distal palmar

triradii, a simian crease in the left palm and a transitionalone in the right, longitudinal groove in the soles of bothfeet along the course of the second metatarsals, pectusexcavatum and widely spaced nipples, small umbilicalhernia, and right undescended testis. Weak peripheralpulses, both femoral and brachial were discerned withdifficulty. Cardiac examination revealed a widely splitsecond sound, an ejection click and 3/6 ejection systolicmurmur best heard in the pulmonary area and left para-sternal zone. The infant was in no distress.The presence of multiple congenital malformations

which did not fit a known syndrome, suggested the possi-bility of a chromosomal abnormality. Surgical inter-vention was therefore deferred and cytogenetic studieswere initiated.Laboratory investigations. An electrocardiogram

showed right ventricular overload and strain.Radiology of the chest revealed cardiomegaly but

no detectable pulmonary parenchymal lesions. Cardiaccatheterization confirmed the clinical diagnosis of pul-monic stenosis and revealed atrial septal defect withleft to right shunt. Post-stenotic dilation of the pul-monary artery and pulmonary hypertension were alsonoted.

FIG. 2. Front (a) and side view (b) of the propositus.

TABLE ITOTAL NUMBER OF CELLS EXAMINED USING DIFFERENT TECHNIQUES

Technique Used Total

G-Banding Q-Banding Orcein No. of Cells Karyotype

Propositus 23 18 34 75 46,XY,del(10) (p13)Mother 12 14 30 56 46,XXFather 19 14 14 47 46,XYSib 5 - 20 25 46,XY

100 Case reports

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Case reports

Propositus(IV. 2) e ai^

.. .....

Mother(III 8)

i . . .

6 7 8 9 10 11 12 X

FIG. 3. Partial karyotypes of the C-group chromosomes (G- and Q-banding) from the propositus and his parents.

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Case reports

Cytogenetic studiesChromosome analysis of the propositus IV.2 using

conventional Orcein staining, Q-banding, and G-banding revealed a 46,XY,del(10) (p13) chromosomeconstitution. The karyotypes of the mother, thefather, and the one living sib showed normal chro-mosomes, with no evidence of a deletion or of anyother detectable rearrangement which might accountfor the chromosome abnormality observed in thepropositus (Table I). Partial karyotypes of the C-group from the propositus, his mother and fatherare shown in Fig. 3 and the position of the deletionin Fig. 4. The breakpoint has been identified at(10) (p13), the material distal to that point being de-leted.

mjJ 7j1

10 10FIG. 4. The position of the deletion of chromosome No. 10.

0.065

E

0.0500-C

> 0.045.-a

Cy- 0.040.

0.035

A Proposituso Father* Mother

0.075 0.060 0.085 0.090 0.095 0.100 0.105 0.110

Relative long arm length

FIG. 5. A plot of the relative arm length of the C-group (6-12)chromosomes for the propositus and his parents.

Chromosome measurements were carried out onthe C-group from five Q-banded cells from each ofthe propositus, his mother, and father; the relativelength, arm ratio, and centromeric index were calcu-lated. Examination ofthe data summarized in Fig. 5,which depicts the mean relative length of p plottedagainst the mean relative length for q, shows thatwith the exception of the del(l0) carried by the pro-positus, none of the chromosomes fall outside of theexpected range of variation for each homologue,thus confirming that no other visually detectablechromosome rearrangement can be found. Thechromosome measurements show that 9 8% of thetotal length, or 27-5% ofthe short arm ofone homo-logue of chromosome 10 is missing. The mostlikely explanation for these observations is a simpleterminal deletion with a breakpoint at (10)(pl3)and loss of the distal segment (10)(pter->p13).Banding of the short arm of chromosome 10 is suchthat a two-break interstitial deletion cannot be ex-cluded. We feel, however, that it is less likely.

Clinical courseWhen his feeding stabilized, the propositus was

discharged, having been fitted with a palatal pros-thesis.At 6 weeks of age he suffered repeated post pran-

dial vomiting which was projectile in character.Subsequent investigations including barium studydisclosed hypertrophic pyloric stenosis, for whichpyloromyotomy was successfully performed at 7weeks.At 10 weeks of age he developed fever, pallor,

and tachypneoa with subcostal indrawing. Exa-mination revealed hepatic enlargement (5 cm be-low the costal margin), muffled first heart sound, anda loud systolic murmur. A chest radiograph dis-closed bilateral broncho-pneumonia and an enlargedcardiac silhouette. An electrocardiogram showedevidence of biventricular overload. Diuretics anddigitalization appeared temporarily to improve hiscondition. However, he ultimately died at 13 weeksof age. Shortly before his death urinalysis showedE. coli and Klebsiella growth.Throughout his hospital stay, the water and

electrolyte balance of the propositus was satis-factorily maintained. He also received antibiotictherapy to combat the infections he developedparticularly the pyelonephritis with possibly septi-cemic complications which ensued a few days beforehis demise.

NecropsyWeight was 3510 g, crown-rump length was 39

cm, and crown-heel length 56 cm. Head circum-

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could account for the substantial clinical abnor-malities observed.

Confirmation of the role of the specific chromo-somal aberration in the genesis of the clinical syn-drome described should await further investigationof similar patterns of malformations. Should thechromosome No. 10 deletion be consistently impli-cated, clinical recognition of the syndrome will berendered more feasible and the management of therespective cases doubtless modified.

The authors are grateful to the excellent technical helpof Miss V. Niewczas-Late and the computer analysis ofMr R. Stuart.

M. H. K. SHOKEIR,* M. RAY, J. L. HAMERTON,F. BAUDER, and H. O'BRIEN

Department of Paediatrics (Division of Genetics),University of Manitoba, Health Sciences Children's

Centre, Winnipeg, Manitoba, Canada

REFRENCES

Alfi, O., Donnell, G. N., Crandall, B. F., Derencsenyi, A., andMenon, R. (1973). Deletion of the short arm of chromosome#9 (46,9p -): a new deletion syndrome. Annales de Genetique, 16,17-22.

Biscatti, G. (1965). Parziale delezione delle braccia lunghe di uncromosome del gruppo 6-12. Pediatria, 73, 660-668.

De Grouchy, J., Royer, P., Salmon, C., and Lamy, M. (1964).Deletion partielle des bras long du chromosome 18. PathologieBiologique, 12, 579-582.

De Grouchy, J., Veslot, J., Bonnette, J., and Roidot, M. (1968). Acase of ?6p - chromosomal aberration. American Jrournal ofDiseases of Children, 115, 93-99.

German, J., Lejeune, J., MacIntyre, M. N., and De Grouchy, J.(1964). Chromosomal autoradiography in the cri du chat syn-drome. Cytogenetics, 3, 347-352.

Hamerton, J. L. (1971). Human Cytogenetics, vol. 2, p. 362. Aca-demic Press, New York.

Le,lo, J. C., Bargman, G. J., Neu, R. L., Kajii, T., and Gardner, L. I.(1967). New syndrome associated with partial deletion of shortarms of chromosome No. 4. journal of the American MedicalAssociation, 202, 434-437.

Lejeune, J., Berger, R., Rethore, M., Archambault, L., Jerome, H.,ThiefEry, S., Aicardi, J., Broyer, M., Lafourcade, J., Cruveiller, J.,and Turpin, R. (1964). Monosomie partielle pour un petit acro-centrique. Comptes Rendus Hebdomadaires des Seances de l'Acadi-mie des Sciences, 259, 4187-4189.

Lejeune, J., Lafourcade, J., Berger, R., Vialatte, J., Boeswillwald,M., Seringe, P., and Turpin, R. (1963). Trois cas de deletionpartielle du bras court d'un chromosome 5. Comptes RendusHebdomadaires des Siances de l'Academie des Sciences, 257, 3098-3102.

Shokeir, M. H. K., Ying, K. L., and Pabello, P. (1973). Deletion ofthe long arm of chromosome no. 7: tentative assignment of theKidd (Jk) locus. Clinical Genetics, 4, 360-368.

Wolf, U., Reinwein, H., Porsch, R., Schroter, R., and Baitsch, H.(1965). Defizienz an den kurzen Armen eines chromosoms Nr. 4.Humangenetik, 1, 397-413.

ference was 37-3 cm, chest circumference was 30 cm,and abdominal circumference was 32-3 cm.

Apart from moderate dilatation of both ventricles,the heart showed bicuspid aortic valve and stenosisof the pulmonary valve.Two more systems showed evidence of con-

genital malformations; the brain which weighed560 g, revealed aplasia of the olfactory bulbs andolfactory tracts. Both kidneys showed evidence ofsepsis-acute pyelonephritis. While the rightkidney was of relatively normal size and weight(31 g), the left kidney weighed less than 7 g, hadonly three calyces and was supplied by tiny, patentvessels. Both kidneys were studded with scatteredmature cartilage throughout the parenchyma. Bothureters were dilated. The right testis was found tobe high in the inguinal canal.

Apart from confirming the clinically visible mal-formations, such as cleft lip and palate involving thealveolus, hard and soft palates, preauricular sinuses,pectus excavatum, and umbilical hernia togetherwith the evidence of pyloromytomy, the remainderof the necropsy disclosed findings consistent withcongestive cardiac failure and urinary sepsis.

DiscussionIt appears plausible that the observed anomalies

in the propositus are ascribable to the partial dele-tion in the short arm of chromosome No. 10. Inconformity with the rest of chromosomal syndromesthere is no underlying common pathogeneticmechanism to account for the diverse and variablephenotypic features.

Since cytogenetic studies performed on the pro-positus' parents and his older sib revealed no de-tectable abnormality it appears most likely that thechromosomal deletion in the propositus had arisende novo. The failure to find any cell with a normalkaryotype in the propositus suggests that the lesionhad arisen either during gametogenesis in the parentsor immediately after fertilization. This inferencehas, of course, important implications in terms ofgenetic counselling for the family, as the risk of re-currence of a similar abnormality must be almostnegligible.

In view of the limitations of the available tech-niques, it cannot be entirely ruled out that the de-leted chromosome is in fact a derivative or recombi-nant chromosome resulting from some type ofchromosome rearrangement carried by one or otherof the parents. There is, however, no evidence forthis and the simplest explanation for the observedfindings is a terminal deletion in the proposituswith significant loss of genetic material. This

* Queen Elizabeth II Scientist.Reprint requests to: Dr M. H. K. Shokeir, Department of Gene-

tics, Health Sciences Centre, Children's Centre, 685 BannatyneAvenue, Winnipeg, Manitoba, R3E OWl, Canada.

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