J Med Genet: first published as 10.1136/jmg.18.6.470 on 1 December 1981. Downloaded from

470 Case reports of a cytogenetic abnormalities in a new case of pure Partial 12q: report partial trisomy 12q, compare the findings with those case and review in the four previous reports, and discuss the cause of the low incidence of this anomaly. SUMMARY A malformed male infant with pure partial trisomy 1 2q (q24. 1 -÷qter), resulting Case report from an unbalanced segregation of a paternal translocation t(2; 12)(q37;q24 1), is The proband was born after an uncomplicated balanced pregnancy and delivery at 36 weeks' gestation. His described. The cytogenetic and clinical abnor- parents, who already had a normal daughter, were malities of the proband are compared with unrelated and healthy. The mother was aged 22 years those of four previously reported cases of and the father 25 years. There was no family history partial trisomy 12q, two of which also appear of spontaneous abortions or stillbirths. At birth the to have pure trisomy of segment 12q24 1-÷12 proband weighed 2650 g and his Apgar score was 9. qter. During the first week he received surgical correction of anal stenosis but otherwise his neonatal period There are, apparently, only four previously reported was normal. cases with any significant partial trisomy 12q,1-4 On presentation at the Clinica Pediatrica, two of which appear to have no other chromosome imbalance.2 4 Here we describe the clinical and

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Case reports 471 University of Catania at 5 weeks, his weight was tip pattern of 5A, 4Lu, and 1W. Both eyes showed 2850 g, length 46.5 cm, and head circumference myopic refraction. 34- 5 cm. He had an odd facies (fig 1, table), a short On re-examination at 4 months, the previously neck with redundant skin folds, clenched hands with noted abnormalities were still evident and the child overlapping fingers and clinodactyly of fingers 3 and showed severe physical and psychomotor retardation. 5, bilateral hammer toes, a sacral dimple, a small penis, and undescended testes. A cardiac systolic CYTOGENETIC STUDIES murmur was audible along the left sternal border and Chromosome preparations were obtained from x-ray investigation revealed enlargement of the left peripheral blood using standard techniques5 and third cardiac arch. Dermatoglyphic studies showed GTG banded6 with a method modified from that of bilateral transverse single palmar creases and Seabright.7 The karyotype of the father was shown hypoplasia of the digital dermal ridges with a finger to be 46,XY,t(2;12)(q37;q24- l) (sub-division of

TABLE Cytogenetic and clinical details in cases ofpartial trisomy 12q Cases with an associated significant Cases with a pure partial trisomy Hirschhorn et all Prieur et a13 Hobolth et al2 Hemming and Brown4 Present case Cytogenetic findings Karyotype 46,XX,der(4), 46,XY,der(9), 46,XY,der(2 1), 46,XX,der( 18), 46,XY,der(2), t(4; 12)(q26;qI 2)pat t(9;12)(q21 ;q24 2) t(12;21)(q24 1 ;pl 1) t(12;18)(q24. 1 ;q23) t(2;12)(q37;q24* I) mat mat pat pat Segregation Adjacent 1 or Adjacent I or Adjacent I or Adjacent I or Adjacent 1 or alternate alternate alternate alternate alternate Trisomy 12ql2- 12qter 12q242-212qter 12q24 1-1 2qter 12q24 1-.I 2qter 12q24* I1_2qter Monosomy 4q26- 4qter 9p2 1-9pter 21 p 1- 21 pter Clinical findings Gestation (wk) 44 36 36 Birthweight (g) 3500 2680 2650 Head Trigonocephaly* Brachycephaly, Brachycephaly, flat Dolichocephaly, copyright. flat top occiput ossified anterior fontanelle Eyes Upward slanting Upward slanting Upward slanting palbebral fissures* palpebral fissures palpebral fissures Ears Poorly lobulated, Poorly lobulated Malformed helix and low set antihelix, poorly lobulated, low set Nose Short nose,* flat Broad bridge, down Small nose, flat Narrow and flat bridge, nasal root,* long turned tip, long bridge long philtrum philtrum* philtrum* Mouth Harelip, cleft palate Micrognathia* Micrognathia* Micrognathia, high http://jmg.bmj.com/ arched palate Neck Redundant skin Short neck, Short neck, folds redundant skin folds redundant skin folds Hands and feet Bilateral hexadactyly Bilateral simian Right hand simian Bilateral simian crease, crease, hammer toes crease, increased clinodactyly of fingers distance between toes 3 and 5, clenched I and 2 of left foot hands, hammer toes Genitalia Cryptorchidism, Cryptorchidism Atretic follicles in Cryptorchidism, hypospadias both ovaries small penis Anus and sacral region Anteriorly displaced Anal stenosis, sacral anus, sacral dimple dimple on September 26, 2021 by guest. Protected Heart Cardiopathy Coarctation of aorta, Cardiopathy Cardiopathy patent foramen ovalis, ventricular hyper- trophy Musculature Subumbilical hernia Hypotonia Hypotonia with agenesis of muscles Others Disc-shaped kidneys, Excessive hair on Single umbilical Thick hair with low- diaphragm-like lower back, angula- artery, increased set hairline, sparse incisions of liver tion of sternum with nipple width, short eyebrows, myopia, prominent xiphoid proximal limbs, weak cry, psycho- process, liver dislocated hips, large motor retardation enlargement, psycho- intestine malrotation, motor retardation pelvic kidney, shallow epiglottic valleculae, brain malformation Survival 6 months Alive at 2 years 6 days (died of Alive at 10 months pneumonia) *Observed in photographs only. J Med Genet: first published as 10.1136/jmg.18.6.470 on 1 December 1981. Downloaded from

472 Case reports 12q24 as in Sanchez et a!8) and that of the proband parental translocation, is unlikely to have contributed 46,XY,der(2),t(2;12)(q37;q24 I)pat (fig 2). The to the abnormal phenotype.'7 However, in the cases proband was thus trisomic for segment 12q24-1I of Hirschhorn et all and Prieur et a!3 the parental 12qter with no detectable monosomy of 2q. translocations were both reciprocal and almost The karyotype of the mother was normal but the symmetrical, resulting in trisomy of nearly the whole family did not consent to cytogenetic investigation of of 12q with monosomy of the distal half of 4q, and other relevant family members, who were, however, trisomy ofsegment 12q24- 22-*lqter with monosomy phenotypically normal. of the distal half of 9p, respectively. In the latter two cases it seems improbable that a Discussion definite distinction can be made between the pheno- typic expression of the partial monosomy and the Full trisomy 12 has not been reported in liveborn partial trisomy 12q. It is possible that in the case of subjects or in cytogenetic surveys of perinatal Hirschhorn et al,' for which few clinical details are mortalities9 10 and has only very occasionally been available, both the partial monosomy 4q and the detected in studies of spontaneous abortuses, in partial trisomy 12q contributed to the abnormalities embryos showing an early arrest of development.1' 12 reported. However, Prieur et a!3 considered that the Similarily, trisomy 12 mosaicism has very rarely been clinical features in the case they described were, in the found.'3 main, consistent with the syndrome associated with Cases with any significant trisomy of long arm partial . material of chromosome 12 are also extremely rare It appears likely, therefore, that a phenotypic with only four previous reports, all involving live- comparison that only includes the cases with a pure born infants.'-4 In contrast, there have been many partial trisomy 12q (present case2 4) will be more liveborn cases with trisomy of short arm material of informative. The clinical features which appear to be chromosome 12, a few including thejuxtacentromeric common to the present case and to either or bo:h of region of 12q, for which a clinical syndrome has been the other two are upward slanting palpebral fissures, 2 delineated.14 Conversely, in balanced translocations poorly lobulated ears2 4 which are low set,2 flat nasal ofchromosome 12 there is far greater involvement of bridge,4 long philtrum,2 micrognathia,2 short neck4copyright. the long arm than the short arm.15 This discrepancy with redundant skin folds,24 simian creases,2 4 may be an indication of the lethality of additional hammer toes,2 cryptorchidism,2 sacral dimple,4 long arm material, which would account for the hypotonia,4 cardiopathy,2 and psychomotor almost complete non-viability of the full trisomic retardation2 (table). condition. However, since the abnormalities in three Although there are as yet too few cases to delineate of the cases of partial trisomy 12q (present case2 3) a phenotype for partial trisomy 12q, it is probable

were compatible with an extended postnatal survival, that the consistent features in the three cases with http://jmg.bmj.com/ the relatively low frequency of partial trisomy 12q in pure trisomy of apparently the same segment the liveborn population may be the result of factors (q24- 1 ---qter) of chromosome 12 will form the basis other than lethality, such as a high level of alternate of a clinical syndrome which will be defined further segregation with a low level ofinterstitial chiasmata.'6 with the accumulation of more data. The case described here and the previous reports of partial trisomy 12q are similar in resulting from The authors wish to thank Mr P J Gregory, Dr D P an alternate or adjacent 1 segregation (with and Duckett, and Dr R A F Macleod for their critical without an uneven number of interstitial chiasmata evaluation of the manuscript, and Professor F on September 26, 2021 by guest. Protected respectively16) of a parental balanced translocation Mollica for helpful advice. (table). The exchange point on chromosome 12 in the cases described by Hobolth et al,2 Hemming and S H ROBERTS,* T MATTINA,*t K M LAURENCE,* Brown,4 and the present report appears to be at G SORGE,t AND L PAVONEt q24- 1, resulting in trisomy of an almost identical *Cytogenetics Unit, Child Health Laboratories, segment of 12q. Furthermore, no monosomy of the Department of Child Health, University Hospital derived chromosome could be detected in the present of Wales, Heath Park, Cardiff, Wales, and case and that of Hemming and Brown,4 because in tClinica Pediatrica, Viale A Doria, both instances either the parental translocation was Universitah di Catania, Italy non-reciprocal or the exchange point was telomeric in the recipient chromosome. In addition, the report References of Hobolth et a!2 can also be considered to be a pure Hirschhorn K, Lucas M, Wallace I. Precise identification trisomy of segment 12q24 1I-2qter since the of various chromosomal abnormalities. Ann Hum Genet absence of 21p, resulting from the reciprocity of the 1973 ;36:375-9. J Med Genet: first published as 10.1136/jmg.18.6.470 on 1 December 1981. Downloaded from

Case reports 473 2 Hobolth N, Jacobsen P, Mikkelsen M. Partial trisomy 12 19 Harrod MJE, Byrne JB, Dev VG, Francke U. Duplication in a mentally retarded boy and translocation (I 2;21) in his 12q mosaicism in two unrelated patients with a similar mother. J Med Genet 1974;11 :299-303. syndrome. Am J Med Genet 1980;7:123-9. 3 Prieur M, Couturier J, Herrault A, Lepintre J, Lejeune J. 20 Zabel B, Baumann W. Partial trisomy 12q. J Med Gener Cited in R&hore M. Syndromes involving chromosomes 1981 ;18:144-6. 4,9 and 12. In: Yunis JJ, ed. New chromosomal syndromes. New York: Academic Press, 1977:119-83. Hemming L, Brown R. Partial trisomy 12q associated with a familial translocation. Clin Geniet 1979;16:25-8. Moorhead PS, Nowell PC, Mellman WJ, Battips DM, Hungerford DA. Chromosome preparations of leukocytes Unilateral radial aplasia and cultured from human peripheral blood. Exp Cell Res 1960;20 :613-6. trisomy 22 mosaicism 6 ISCN (1978). An international system for human cyto- genetic nomenclature. Birth Defects 1978;14:No 8. SUMMARY A child with unilateral radial aplasia, Seabright M. A rapid banding technique for human chromosomes. Lancet 1971 ;ii:971-2. asymmetry, other malformations, and severe 8 Sanchez 0, Yunis JJ, Escobar JI. Partial trisomy 11 in a physical and mental retardation is reported. child resulting from a complex maternal rearrangement of In blood and bone marrow cultures a low chromosomes 11, 12, and 13. Humangenetik 1974;22: 59-65. mosaicism for trisomy 22 was found. In a few 9 Machin GA, Crolla JA. Chromosome constitution of 500 cells a was missing. The im- infants dying during the perinatal period. Humangenetik on 1974;23:183-98. portance of early cytogenetic analysis large 10 Kuleshov NP. Chromosome anomalies of infants dying numbers of cells is emphasised, especially in during the perinatal period and premature newborn. Hum cases ofasymmetry where mosaicism is suspected. Genet 1976;31:151-60. Boue J, Daketse MJ, Deluchat C, Ravise N, Yvert F, Boue A. Identification par les bandes Q et G des anomalies Radial dysplasia is a relatively common limb chromosomiques dans les avortements spontanes. Ann malformation which has been associated with major Genet (Paris) 1976;19:233-9. anomalies in various systems, mostly genitourinary, 12 Kajii T, Ferrier A, Niikawa N, Takahara H, Ohama K, and cardiac. It occur copyright. Sugandhi A. Anatomic and chromosomal anomalies in skeletal, gastrointestinal, may 639 spontaneous abortuses. Hum Genet 1980;55:87-98. within a definite syndrome, for example, thrombo- 13 Richer CL, Bleau G, Chapdelaine A. Trisomy 12 cytopenia and absent radius (TAR), Holt-Oram mosaicism in an infertile man. Can J Genet Cytol 1977 ;19: syndrome, Fanconi's anaemia, and VATERL 565-7. and it has also been in chromo- o Kondo 1, Hamaguchi H, Haneda T. Trisomy 12p association, reported syndrome: de novo occurrence of trisomy 12p in a somal disorders like trisomy 13 and 18.1 mentally retarded boy. Hum Genet 1979;46:135-40. We describe a child with total unilateral radial 15 Biederman B, Bowen P. Balanced translocations involving aplasia associated with a clustering of defects on the chromosome 12: report of a case and possible evidence for same side, in whom 22 mosaicism was http://jmg.bmj.com/ position effect. Ann Genet (Paris) 1976 ;19 :257-60. Hamerton JL. General cytogenetics. In: Human cyto- demonstrated. genetics. Vol 2. New York: Academic Press, 1971:248-54. 17 Neilsen J, Friedrich V, Hreidarsson AB. Frequency of Case report of short arm satellites in acrocentric chromosomes. J Med Genet 1974;1 1 :177-80. A 2900 g female child was born after a normal Requests for reprints to Mr S H Roberts, Cytogenetics pregnancy and delivery to non-consanguineous Unit, Child Health Laboratories, Department of parents of Arabic origin. The 25-year-old mother, Child Health, University Hospital of Wales, Heath the 36-year-old father, and the four other children on September 26, 2021 by guest. Protected Park, Cardiff CF4 4XN. were healthy. There was no history of any congenital anomaly in the family. Note added in proof A clustering of malformations was evident on the Since submission of this paper five cases of pure, left side including a small palpebral fissure with slight or almost pure, partial trisomy of I2q24 have been ptosis, hypotrophy of the cheek, a low set ear with reported.18-20 The many features common to these abnormal configuration of the helix, and mild and to the three cases of pure partial trisomy stenosis of the external auditory canal. Total left described above support the suggestion in the radial aplasia with absent thumb was present (fig 1). concluding paragraph that pure trisomy of this The left forearm, hand, and the four medial region of chromosome 12 results in an identifiable fingers were smaller than those on the right side and clinical syndrome. there was colateral clinodactyly of the little finger References with only one transverse crease on the left. 18 de Muelenaere A, Fryns JP, van den Berghe H. Partial Repeated blood counts, including platelet and distal 12q trisomy. Ann Genet (Paris) 1980;23:251-3. Received for publication 14 January 1981