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Prenatal diagnosis of an interstitial 12q chromosome deletion
Annales de génétique 47 (2004) 177–179 www.elsevier.com/locate/anngen
Case Report
Prenatal diagnosis of an interstitial 12q chromosome deletion C. Pérez Sánchez a,*, F. Ayensa b, E. Lloveras a, L. Zamora a, V. Cirigliano c, E. Pérez a, A. Plaja a a
Departament de Citogenètica, General Lab Laboratori d’Anàlisi, C/ Londres, 45, Barcelona 08036, Spain b Departamento de Ginecología, Hospital Mútua del Carmen, Granollers, Spain c Departament de Biologia Mollecular, Lab 2 Laboratori d’Anàlisi, Barcelona, Spain Received 31 July 2003; accepted 9 October 2003 Available online 19 November 2003 We present an interstitial 12q deletion detected in a prenatal diagnosis.
Abstract Rearregements involving long arm of chromosome 12 are rare events. To our knowledge, we present the first case of an interstitial deletion of the long arm of chromosome 12 in a prenatal diagnosis. A review of the literature is included in our report. © 2003 Elsevier SAS. All rights reserved. Keywords: Interstitial 12q deletion; Prenatal diagnosis; Sonographic marker
1. Case report Rearrangements involving long arm of chromosome 12 are rare events. We report an interstitial deletion of the long arm of chromosome 12 with breakpoints q13 and q15. To our knowledge this is the first report of a prenatal detection of a deletion of chromosome 12. We describe a fetus in a 34-years-old pregnant. Amniocentesis was performed at 19 weeks of pregnancy following the observation of a short femur (femur length 26.4 mm, in the fifth percentile) in the fetus by ultrasonography. Uncultured amniotic fluid QF-PCR, performed as described by Cirigliano et al. [1], discarded numerical anomalies involving chromosomes 13, 18, 21, X and Y. * Corresponding author. Tel.: +34-93-405-35-55; fax: +34-93-419-91-85. E-mail address: [email protected] (C. Pérez Sánchez). © 2003 Elsevier SAS. All rights reserved. doi:10.1016/j.anngen.2003.10.006
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C. Pérez Sánchez et al. / Annales de génétique 47 (2004) 177–179
Fig. 1. Interstitial deletion of the long arm of chromosome 12 with q13 and q15 breakpoints.
Conventional cytogenetic analysis of amniotic fluid cells from two independent flasks was performed using G-banding. All 20 metaphases analyzed showed an interstitial deletion of the long arm of chromosome 12 with q13 and q15 breakpoints (Fig. 1). Parental karyotypes were both normal. On the basis of the cytogenetic results, parents decided on termination of the pregnancy in the 22 weeks of pregnancy and accepted necropsy. Physical examination revealed a male fetus with mild dysmorphic features, a weight of 478 g, a crown-heel length of 26 cm and a crown-rump length of 20 cm. Craniofacial features included micrognathia, and low set ears. Thigh, leg and foot lengths were 5, 4.8 and 4 cm, respectively. Upper and lower arms measured 4.5 and 4.2 cm, respectively. Necropsy revealed a horseshoe shaped kidney. Literature involving chromosome 12q deletions is scarce. There are a few reports related with born or spontaneously delivered probands with deletions of different size and location. Clinical findings reported in cases with 12q deletions include microcephalia, hypertelorism, micrognatia, upward slanting palpebral fissures, strabismus, broad nasal bridge, long and low set ears, hearing loss, bilateral cleft lip and palate, high arched palate, macrostomia, overriding of second and fifth fingers bilaterally, rocker bottom feet, syndactily of second and third toes, cardiac abnormalities, and psychomotor and growth retardation [3,5,6,9,10]. No characteristic common phenotype emerges by the moment from these few cases, but our case shares some clinical features with that described by Meinecke and Meinecke (1985), with a deletion 12(q13q15) partly overlapping that of present case: both cases share a low birth weight, low set ears, retrognatia, minor cardiac abnormalities and growth
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retardation. Meinecke and Meinecke’s patient died at 10 weeks, so mental status could not be evaluated. Sonographic and biochemicals markers are also usually focused to the detection of numerical chromosome abnormalities. Short femur may have the added value of its association with a broader range of chromosome abnormalities [2,4,7,8].
References [1]
V. Cirigliano, M. Ejarque, M.O. Cañadas, E. Lloveras, A. Plaja, M. del Mar Perez, C. Fuster, J. Egozcue, Clinical application of multiplex quantitative fluorescent polymerase chain reaction (QF-PCR) for the rapid prenatal detection of common chromosome aneuploidies, Mol. Hum. Reprod 7 (2001) 1001–1006. [2] L.B. Feuchtbaum, R.J. Currier, F.W. Lorey, G.C. Cunningham, Prenatal ultrasound findings in affected and unaffected pregnancies that are scre-positive for trisomy 18: the California experience, Prenatal Diagn. 20 (2000) 293–299. [3] M. Gallego, C. Barreiro, M. Pérez, H. Arroyo, J. Menehem, A new case of interstitial 12q deletion, Int. Pediatr 15 (1) (2000) 37–40. [4] T. Hsu, F. Kung, C. Ou, P. Hsiao, F. Huang, C. Changchien, S. Chang, Prenatal diagnosis of de novo interstitial deletion of proximal 4q bu maternal serum screening for Down syndrome, Prenatal Diagn. 18 (1998) 1323–1327. [5] P. Meinecke, R. Meinecke, Multiple malformation syndrome including cleft lip and palate and cardiac abnormalities due to an interstitial deletion of chromosome 12q, J. Med. Genet 24 (1985) 187. [6] P. Sathya, J.D. Darrell, V. Freeman, B. Paes, M.J.M. Nowaczyk, De novo delection 12q: report of a patient with 12.24.31q24.33 delection, Am. J. Med. Genet 84 (1999) 116–119. [7] R. Slim, J. Soulié, J. Hotmar, B. Lecolier, G. Bercau, Bernheim, A prenatal identification of an isochromosome for the short arm of the Y i(Yp), by cytogenetic and molecular analyses, Prenatal Diagn. 14 (1994) 23–28. [8] B.D. Sohl, A.L. Scioscia, M.E. Budorick, T.R. Moore, Utility of minor ultrasonographic markers in the prediction of abnormal fetal karyotype at a prenatal diagnostic center, Am. J. Obstet. Gynecol 181 (4) (1999) 898–903. [9] H. Tonoki, S. Saitoh, K. Kobayashi, Patient with del(12)(q12q13.12) manifesting abnormalities compatible with Noonan syndrome, Am. J. Med. Genet 75 (1998) 416–418. [10] M.S. Watson, L. McAllister-Barton, M.J. Mahoney, W.R. Breg, Delection (12)(q15q21.2), J. Med. Genet 26 (1989) 343–345.
Case Report
Prenatal diagnosis of an interstitial 12q chromosome deletion C. Pérez Sánchez a,*, F. Ayensa b, E. Lloveras a, L. Zamora a, V. Cirigliano c, E. Pérez a, A. Plaja a a
Departament de Citogenètica, General Lab Laboratori d’Anàlisi, C/ Londres, 45, Barcelona 08036, Spain b Departamento de Ginecología, Hospital Mútua del Carmen, Granollers, Spain c Departament de Biologia Mollecular, Lab 2 Laboratori d’Anàlisi, Barcelona, Spain Received 31 July 2003; accepted 9 October 2003 Available online 19 November 2003 We present an interstitial 12q deletion detected in a prenatal diagnosis.
Abstract Rearregements involving long arm of chromosome 12 are rare events. To our knowledge, we present the first case of an interstitial deletion of the long arm of chromosome 12 in a prenatal diagnosis. A review of the literature is included in our report. © 2003 Elsevier SAS. All rights reserved. Keywords: Interstitial 12q deletion; Prenatal diagnosis; Sonographic marker
1. Case report Rearrangements involving long arm of chromosome 12 are rare events. We report an interstitial deletion of the long arm of chromosome 12 with breakpoints q13 and q15. To our knowledge this is the first report of a prenatal detection of a deletion of chromosome 12. We describe a fetus in a 34-years-old pregnant. Amniocentesis was performed at 19 weeks of pregnancy following the observation of a short femur (femur length 26.4 mm, in the fifth percentile) in the fetus by ultrasonography. Uncultured amniotic fluid QF-PCR, performed as described by Cirigliano et al. [1], discarded numerical anomalies involving chromosomes 13, 18, 21, X and Y. * Corresponding author. Tel.: +34-93-405-35-55; fax: +34-93-419-91-85. E-mail address: [email protected] (C. Pérez Sánchez). © 2003 Elsevier SAS. All rights reserved. doi:10.1016/j.anngen.2003.10.006
178
C. Pérez Sánchez et al. / Annales de génétique 47 (2004) 177–179
Fig. 1. Interstitial deletion of the long arm of chromosome 12 with q13 and q15 breakpoints.
Conventional cytogenetic analysis of amniotic fluid cells from two independent flasks was performed using G-banding. All 20 metaphases analyzed showed an interstitial deletion of the long arm of chromosome 12 with q13 and q15 breakpoints (Fig. 1). Parental karyotypes were both normal. On the basis of the cytogenetic results, parents decided on termination of the pregnancy in the 22 weeks of pregnancy and accepted necropsy. Physical examination revealed a male fetus with mild dysmorphic features, a weight of 478 g, a crown-heel length of 26 cm and a crown-rump length of 20 cm. Craniofacial features included micrognathia, and low set ears. Thigh, leg and foot lengths were 5, 4.8 and 4 cm, respectively. Upper and lower arms measured 4.5 and 4.2 cm, respectively. Necropsy revealed a horseshoe shaped kidney. Literature involving chromosome 12q deletions is scarce. There are a few reports related with born or spontaneously delivered probands with deletions of different size and location. Clinical findings reported in cases with 12q deletions include microcephalia, hypertelorism, micrognatia, upward slanting palpebral fissures, strabismus, broad nasal bridge, long and low set ears, hearing loss, bilateral cleft lip and palate, high arched palate, macrostomia, overriding of second and fifth fingers bilaterally, rocker bottom feet, syndactily of second and third toes, cardiac abnormalities, and psychomotor and growth retardation [3,5,6,9,10]. No characteristic common phenotype emerges by the moment from these few cases, but our case shares some clinical features with that described by Meinecke and Meinecke (1985), with a deletion 12(q13q15) partly overlapping that of present case: both cases share a low birth weight, low set ears, retrognatia, minor cardiac abnormalities and growth
C. Pérez Sánchez et al. / Annales de génétique 47 (2004) 177–179
179
retardation. Meinecke and Meinecke’s patient died at 10 weeks, so mental status could not be evaluated. Sonographic and biochemicals markers are also usually focused to the detection of numerical chromosome abnormalities. Short femur may have the added value of its association with a broader range of chromosome abnormalities [2,4,7,8].
References [1]
V. Cirigliano, M. Ejarque, M.O. Cañadas, E. Lloveras, A. Plaja, M. del Mar Perez, C. Fuster, J. Egozcue, Clinical application of multiplex quantitative fluorescent polymerase chain reaction (QF-PCR) for the rapid prenatal detection of common chromosome aneuploidies, Mol. Hum. Reprod 7 (2001) 1001–1006. [2] L.B. Feuchtbaum, R.J. Currier, F.W. Lorey, G.C. Cunningham, Prenatal ultrasound findings in affected and unaffected pregnancies that are scre-positive for trisomy 18: the California experience, Prenatal Diagn. 20 (2000) 293–299. [3] M. Gallego, C. Barreiro, M. Pérez, H. Arroyo, J. Menehem, A new case of interstitial 12q deletion, Int. Pediatr 15 (1) (2000) 37–40. [4] T. Hsu, F. Kung, C. Ou, P. Hsiao, F. Huang, C. Changchien, S. Chang, Prenatal diagnosis of de novo interstitial deletion of proximal 4q bu maternal serum screening for Down syndrome, Prenatal Diagn. 18 (1998) 1323–1327. [5] P. Meinecke, R. Meinecke, Multiple malformation syndrome including cleft lip and palate and cardiac abnormalities due to an interstitial deletion of chromosome 12q, J. Med. Genet 24 (1985) 187. [6] P. Sathya, J.D. Darrell, V. Freeman, B. Paes, M.J.M. Nowaczyk, De novo delection 12q: report of a patient with 12.24.31q24.33 delection, Am. J. Med. Genet 84 (1999) 116–119. [7] R. Slim, J. Soulié, J. Hotmar, B. Lecolier, G. Bercau, Bernheim, A prenatal identification of an isochromosome for the short arm of the Y i(Yp), by cytogenetic and molecular analyses, Prenatal Diagn. 14 (1994) 23–28. [8] B.D. Sohl, A.L. Scioscia, M.E. Budorick, T.R. Moore, Utility of minor ultrasonographic markers in the prediction of abnormal fetal karyotype at a prenatal diagnostic center, Am. J. Obstet. Gynecol 181 (4) (1999) 898–903. [9] H. Tonoki, S. Saitoh, K. Kobayashi, Patient with del(12)(q12q13.12) manifesting abnormalities compatible with Noonan syndrome, Am. J. Med. Genet 75 (1998) 416–418. [10] M.S. Watson, L. McAllister-Barton, M.J. Mahoney, W.R. Breg, Delection (12)(q15q21.2), J. Med. Genet 26 (1989) 343–345.