Interstitial deletion of chromosome 5 in a neonate due to maternal insertion ins(8;5)(p23;q33q35)код для вставкиСкачать
American Journal of Medical Genetics 86:289–293 (1999) Brief Clinical Report Interstitial Deletion of Chromosome 5 in a Neonate Due to Maternal Insertion, ins(8;5)(p23;q33q35) Barbara Gibbons,1,3* Siew Yee Tan,1 Su Keyau Kee,1 Roger Quaife,1 and Seh Teen Lim2 1 Cytogenetics Laboratory, Gleneagles Hospital, Singapore Department of Paediatrics, Hospital Sultanah Aminah, Johore Bahru, Malaysia 3 Cytogenetics Laboratory, Academic Department of Haematology, Royal Free and University College Medical School, London, United Kingdom 2 We describe an infant girl with an interstitial deletion of chromosome bands 5q33 to 5q35 inherited from a maternal interchromosomal insertion ins(8;5)(p23;q33q35) which was demonstrated by fluorescent in situ hybridization with whole chromosome paints. Physical anomalies included hypertonicity, microcephaly, short neck, apparently low-set ears, micrognathia, camptodactyly, mild rocker bottom feet, and hammer toe. Cardiac anomalies included a large ventricular septal defect, patent ductus arteriosus, pulmonary hypertension and hypoplastic right ventricle. She died at age 3 months. Am. J. Med. Genet. 86:289–293, 1999. © 1999 Wiley-Liss, Inc. KEY WORDS: interstitial 5q deletion; partial 5q deletion; del(5) (q33q35); maternal insertion INTRODUCTION There are few descriptions of small terminal or subterminal deletions of distal 5q, here defined as 5q315qter. The largest deletion, 5q31.3-qter was described by Lazjuk et al.  in a malformed, stillborn infant. Smaller deletions seen in liveborn infants have been described as del(5)(q33q34) [Giltay et al., 1997], 5q33ter [Flannery et al., 1988], del(5)(q35) [Joseph et al., 1990], del(5)(q35.1) [Kleczkowska et al., 1993], and del(5)(q35.3) [Stratton et al., 1994]. A further patient *Correspondence to: Barbara Gibbons, BSc(Hons) FRCPath, Cytogenetics Laboratory, Queen Square House, Second Floor, Institute of Neurology, Queen Square, London W1CN 3BG, UK. Received 7 October 1998; Accepted 21 April 1999 © 1999 Wiley-Liss, Inc. with deletion of 5q from the pre-banding era was described by Lindenbaum and Butler . This small number of cases has not permitted the delineation of a recognizable resulting syndrome. Here we describe an infant girl with an interstitial deletion of 5q33 to 5q35 inherited from a maternal interchromosomal insertion ins(8;5)(p23;q33q35). Although more proximal interstitial deletions due to intrachromosomal insertion involving 5q have been previously described [Barber et al., 1994; Cross et al., 1992], this is the first report of interstitial distal deletion of 5q arising from a parental balanced interchromosomal insertion. CLINICAL REPORT The patient, a girl, was born to non-consanguineous Chinese parents at term with birth weight of 3.1 kg (50th centile), length 55 cm (90th centile for weight), and OFC 33.5 cm (<10th centile). No complications of pregnancy or delivery were noted. Family history was unremarkable. At birth it was observed that the infant had some facial anomalies and poor feeding. On the 21st day of life she developed recurrent cyanotic spells following bouts of coughing. On admission she was found to be hypertonic with stiffness of all four limbs and in respiratory distress with intermittent cyanosis. She was ventilated mechanically for 1 week. Physical anomalies included microcephaly, hypertelorism with prominent epicanthic folds, short neck with redundant skin, apparently low-set ears with normal pinna and helix, micrognathia (Fig. 1), camptodactyly, mild rocker bottom feet, and a hammer toe (Fig. 2). Two-dimensional echocardiogram showed a large ventricular septal defect, patent ductus arteriosus, pulmonary hypertension, and hypoplastic right ventricle. She remained in the hospital for another month during which she was treated for heart failure and intercurrent infection. She was discharged at 2 months with anti-heart-failure medication. However, she was readmitted again 10 days later for pneumonia which 290 Gibbons et al. Fig. 1. A,B: Facial appearance of the patient. needed ventilation. She died 2 weeks later. Consent for autopsy was not granted. CYTOGENETIC FINDINGS Karyotyping was performed on G-banded metaphase chromosomes after routine peripheral blood culture. Synchronization by thymidine block [Gosden et al., 1992] was used to obtain high resolution G-banded chromosomes. Analysis of the patient’s chromosomes showed an apparent deletion of chromosome 5q. The parents were karyotyped to investigate if either was a translocation carrier. The father’s karyotype was normal 46,XY but the mother was found to be a carrier of a rearrangement between chromosomes 5 and 8 (Fig. 3). Metaphase cells from both the patient and her mother were examined after fluorescent in situ hybridization (FISH) with whole chromosome paints Fig. 2. A,B: Camptodactyly and mild rocker bottom feet. Inherited Deletion 5q 291 for chromosomes 5 and 8 (WCP 5, WCP 8, Cytocell), which was performed following the manufacturer’s instructions. Hybridization showed that the maternal rearrangement was a balanced insertion (Fig. 4), the mother’s karyotype being 46,XX,ins(8;5)(p23;q33q35) and the child’s karyotype 46,XX,der(5)ins(8;5)(p23; q33q35)mat. DISCUSSION Fig. 3. Partial karyotypes of the patient and her mother showing the normal and derivative chromosomes of the ins(8;5)(p23;q33q35). The mother has both derivative chromosomes, the patient has the derivative chromosome 5 but not the derivative 8. Fig. 4. and 8. The main clinical findings of the present and previously described cases with distal deletion of chromosome 5 are presented in Table I. The common region of deletion in the cases of Kleczkowska et al. , Joseph et al. , Flannery et al. , Lazjuk et al. , and the present case was 5q35.1. However, the deletions are of different size (Fig. 5) and not surprisingly, although respiratory and feeding problems, limb anomalies, and non-specific facial anomalies were reported, no specific clinical syndrome has been delineated. Neither the patient of Flannery et al.  nor Patient 2 of Lazjuk et al.  had pure deletions of chromosome 5q; the former had a ring chromosome involving deletion of distal 5p and the latter had duplication of band 10q26 arising from a maternal translocation, thus complicating the clinical picture. Metaphase cell from the patient’s mother showing insertion ins(8;5)(p23;q33q35) by FISH with whole chromosome paints for chromosomes 5 292 Gibbons et al. TABLE I. Clinical Manifestations in Partial 5q Deletion Syndrome* Patient Stratton et al., 1994 Kleczkowska et al., 1993 Deleted segment Gender q35.3-ter M q35.1-ter F q35-ter F Age 15 m 9m died 19 d Birth weight Developmental delay Respiratory problems Feeding problems Limb anomalies Clinodactyly Camptodactyly Fingers 3913 g mild 2980 g severe 3448 g Edema of the hands/feet Nails Head anomalies Micro/macrocephaly Brachycephaly High protruding forehead Potter-like facies Epicanthus Telecanthus/hypertelorism Anteverted nares Wide/flat nasal bridge High arched palate Retrognathia/hypognathia Ear anomalies CNS anomalies Dandy-Walker malformation hydrocephalus polymicrogyria cortical anomalies heterotopia agenesis corpus callosum abnormal neuronal migration Hypo/hypertonic Cardiac anomalies Urogenital anomalies Ano/rectal anomalies Redundant nuchal or neck skin Abnormal chest wall Dermatoglyphics Excess fingertip whorls Single transverse palmar crease Joseph et al., 1990 Flannery et al., 1988 Lazjuk et al., 1985 ?p14?q33 M hermaphrodite 2.5 m Lindenbaum and Butler, 1971 Gibbons et al., 1999 Giltay et al., 1997 q31.3-ter F ? M q33q35 F q33q34 F stillbirth 32 w 9m died 3 m 6y 3030 g severe + 3100 g 3200 g mild severe + + + + + + short + short syndactyly long hypoplastic hyperconvex macro micro + + + macro + micro + + + + + + + + + + + micro + + + + + + + + + + + + + + + + + + + + + + + + + + + low-set + + + + + + hypo ASD hyper PDA multiple inc VSD ASD diastasis recti + + + hypo VSD diastasis recti hypo + absent anus abnormal rectum hyper + + + + + + hyper multiple inc VSD PDA + + + *inc ⳱ including; VSD ⳱ ventricular septal defect; ASD ⳱ atrial septal defect; PDA ⳱ patent ductus arteriosus. The only notable facial similarity is between the patients of Stratton et al.  and Kleczkowska et al. , both with small distal deletions involving only band 5q35. However, cardiac anomalies were noted in 5 patients, and ano–rectal anomalies in 3 patients, suggesting the presence of developmental genes at a distal 5q locus. The 3 hypotonic infants [Flannery et al., 1988; Lindenbaum and Butler, 1971; Stratton et al., 1994] also had an excess of fingertip whorls and/ or evidence of edema of the hands and/or feet as has been seen in patients with more proximal 5q deletion [Flannery et al., 1988]. Although CNS data were only available on 5 patients, 4 had CNS anomalies and of these the patient of Joseph et al.  had abnormal cortical layers, heterotopias, polymicrogyria, and a Dandy-Walker malformation. Patient 2 of Lazjuk et al.  had abnormal neuronal migration, and Lindenbaum and Butler  described a child with polymicrogyria and absent corpus callosum. Although chromosome breakpoints are uncertain in the case of Lindenbaum and Butler , the data suggest the possibility of a distal 5q locus affecting neuronal migration. The deletion breakpoints in these cases have been interpreted on the basis of G-banding and more precise breakpoint assignments would require the application of band-specific probes as illustrated by Giltay et al. . Elucidation of clear clinical syndromes for deletions of distal 5q awaits further cases and precise mapping of the breakpoints involved. Inherited Deletion 5q 293 chromosome 5 resulting from a maternal intrachromosomal insertion. J Med Genet 31:312–316. Cross I, Delhanty J, Chapman P, Bowles LV, Griffin D, Wolstenholme J, Bradburn M, Brown J, Wood C, Gunn A, Burn J. 1992. An intrachromosomal insertion causing 5q22 deletion and familial adenomatous polyposis coli in two generations. J Med Genet 29:175–179. Flannery DB, Rogers WG, Byrd JR. 1988. Ring chromosome 5. Clin Genet 34:74–78. Giltay JC, Gerssen-Schoorl KBJ, Luitse GHJ, Dauwerse HG (1997). A case of de novo interstitial deletion of chromosomne 5(q33q34). Clin Genet 52:173–176. Gosden CM, Davidson C, Robertson M. 1992. Lymphocyte Culture in Human Cytogenetics A Practical Approach. Chapter 2. Eds Rooney DE and Czepulkowski BH. Oxford. IRL Press. Joseph P, Kimm J, Kalyan-Raman UP, Nixon JP. Hiller J. 1990. Terminal deletion of the long arm of chromosome 5. Am J Hum Genet 47:A31. Fig. 5. Idiogram of chromosome 5 showing the deletions of (a) Stratton et al. , (b) Kleczkowska et al. , (c) Joseph et al. , (d) Flannery et al. , (e) Lazjuk et al. , (f) present case, and (g) Giltay et al. . Kleczkowska A, Fryns JP, van den Berghe H. 1993. A distinct multiple congenital anomalies syndrome associated with distal 5q deletion (q35.1qter). Ann Genet 36:126–128. Lazjuk GI, Lurie IW, Kirillova IA, Zaletajev DV, Gurevich DB, Shved IA, Ostrovskaya TI. 1985. Partial trisomy 5q and partial monosomy 5q within the same family. Clin Genet 28:122–129. REFERENCES Lindenbaum RH, Butler LJ. 1971. Child with multiple anomalies and a group B(4-5) long arm deletion (Bq-). Arch Dis Child 46:99–101. Barber JC, Ellis KH, Bowles LV, Delhanty JD, Ede RF, Male BM, Eccles DM. 1994. Adenomatous polyposis coli and a cytogenetic deletion of Stratton RF, Tedrowe NA, Tolworthy JA, Patterson RM, Ryan SG, Young RS. 1994. Deletion 5q35.3. Am J Med Genet 51:150–152.