- Email: [email protected]
Prenatal Diagnosis of Partial Trisomy 3p (3p21→pter) and Partial Monosomy 11q (11q23→qter) Associated with Abnormal Sonographic Findings of Holoprosencephaly, Orofacial Clefts, Pyelectasis and a Unilateral Duplex Renal System
CASE REPORT
Prenatal Diagnosis of Partial Trisomy 3p (3p21pter) and Partial Monosomy 11q (11q23qter) Associated with Abnormal Sonographic Findings of Holoprosencephaly, Orofacial Clefts, Pyelectasis and a Unilateral Duplex Renal System Chih-Ping Chen,1,2,3,4* Tzu-Hao Wang,5 Chyi-Chyang Lin,6 Fuu-Jen Tsai,4,6 Lie-Jiau Hsieh,7 Wayseen Wang2,8 Patients with partial trisomy 3p seldom present major dysmorphic features, and holoprosencephaly occurs in only 10% of the cases with partial trisomy 3p. It has been suggested that multiple genetic hits or environmental exposures are required for the clinical expression of holoprosencephaly. At 16 weeks of gestation, prenatal sonography identified a fetus with holoprosencephaly, orofacial clefts, pyelectasis, and a unilateral duplex renal system. Amniocentesis revealed the karyotype of 46,XX,der(11)t(3;11)(p21;q23)pat with partial trisomy 3p (3p21pter) and partial monosomy 11q (11q23qter). The pregnancy was subsequently terminated. Postnatally, the proband showed hypotelorism, a depressed nasal bridge, orofacial clefts and holoprosencephaly-premaxillary agenesis. The present case provides evidence that partial trisomy 3p/ monosomy 11q can be a genetic cause of holoprosencephaly and del(11)(q23qter) is associated with a duplex renal system. [J Formos Med Assoc 2008;107(10):822–826] Key Words: duplex renal system, holoprosencephaly, orofacial clefts, partial monosomy 11q, partial trisomy 3p, pyelectasis
and hydronephrosis.1 Partial distal monosomy 11q is characterized by developmental delay, psychomotor retardation, craniofacial dysmorphism (trigonocephaly, hypertelorism, a broad and flat nasal bridge, a carp shaped mouth, a high arched palate, micrognathia, low-set malformed ears), congenital heart defects (ventricular septal defects, truncus arteriosus, aortic arch defects), renal anomalies (renal duplication, hydronephrosis),
Partial distal trisomy 3p is characterized by mental retardation and minor dysmorphism such as a square shaped face with full cheeks, hypertelorism, epicanthus, a thick and short nose, a prominent philtrum, full lips, a large mouth with downturned corners, micrognathia, and retrognathia. Partial distal trisomy 3p may occasionally be associated with major anomalies such as holoprosencephaly (HPE), facial clefts, cardiac anomalies,
©2008 Elsevier & Formosan Medical Association .
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Departments of 1Obstetrics and Gynecology, and 2Medical Research, Mackay Memorial Hospital, Taipei; 3Department of Biotechnology, Asia University, Taichung; 4School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung; 5Department of Obstetrics and Gynecology, Lin-Kou Medical Center, Chang-Gung Memorial Hospital, Chang-Gung University, Taoyuan; 6Department of Medical Genetics, China Medical University Hospital, Taichung; 7 Department of Life Sciences, Chung Shan Medical University, Taichung; and 8Department of Bioengineering, Tatung University, Taipei, Taiwan. Received: May 11, 2007 Revised: June 15, 2007 Accepted: August 7, 2007
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*Correspondence to: Dr Chih-Ping Chen, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, 92, Section 2, Chung-Shan North Road, Taipei, Taiwan. E-mail: [email protected]
J Formos Med Assoc | 2008 • Vol 107 • No 10
Partial trisomy 3p/monosomy 11q
ocular malformations (ptosis, colobomas, cataracts, glaucoma, strabismus, telecanthus), limb anomalies (talipes equinovarus, clino- or camptodactyly, syndactyly), a short neck, widely spaced nipples, and thrombocytopenia or pancytopenia.2 Here, we present a rare case of prenatally detected partial trisomy 3p/monosomy 11q associated with striking abnormal sonographic findings.
Case Report A 30-year-old woman, gravida 4, para 2, was referred for genetic counseling at 16 weeks of gestation because of fetal anomalies on prenatal
ultrasound. The woman’s karyotype was 46,XX. Her husband was a carrier of a balanced reciprocal translocation and had a karyotype of 46,XY,t(3;11) (p21;q23). Four years previously, the woman gave birth to an abnormal fetus with multiple malformations including a Dandy-Walker variant and trigonocephaly, and a karyotype of 46,XX,der(11) t(3;11)(p21;q23)pat. During this pregnancy, level II sonograms at 16 weeks of gestation showed alobar HPE, orofacial clefts, pyelectasis and a left duplex renal system (Figure 1). Other biometric measurements were normal. Amniocentesis revealed a karyotype of 46,XY, der(11)t(3;11)(p21;q23)pat. Owing to an unbalanced segregation of the paternal t(3;11), the fetus
A
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C
D
Figure 1. Prenatal ultrasound at 16 weeks of gestation shows: (A) alobar holoprosencephaly with the presence of a single ventricle and fused thalami; (B) left duplex renal system (arrows) with a dilated pelvis in the lower pole and pyelectasis of the right kidney (*); (C) orofacial clefts and facial dysmorphism; (D) Facial appearance at birth. J Formos Med Assoc | 2008 • Vol 107 • No 10
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had two normal chromosomes 3, one normal chromosome 11, and one derivative chromosome 11, resulting in partial trisomy 3p (3p21pter) and partial monosomy 11q (11q23qter) (Figure 2). The derivative chromosome 11 was characterized by fluorescence in situ hybridization using the 3p/3q and 11p/11q specific subtelomeric probes (Vysis, Downers Grove, IL, USA) (Figures 3 and 4). The pregnancy was subsequently terminated, and a 100-g male fetus was delivered. At birth, the proband showed hypotelorism, a depressed nasal bridge, and orofacial clefts. Autopsy confirmed the diagnosis of HPE-premaxillary agenesis (HPE-PMA).
p21 Father q23
3
3
11
3
der(11)
11
Figure 2. Chromosome preparation shows the balanced reciprocal translocation identified in the father and chromosomes 3, 11 and der(11) in the proband. Arrows indicate the breakpoints.
B der(11)
der(11)
3
11
3
11
Figure 3. Fluorescence in situ hybridization study using 3p (green)/3q (red) TEL probes shows that der(11) is stained with a green signal by the 3p subtelomeric probe.
3
A
3
B 3
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der(11)
Proband
A
Figure 4. Fluorescence in situ hybridization study using 11p (green)/11q (red) TEL probes shows absence of a red signal by the 11q subtelomeric probe on der(11).
der(3)
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der(11)
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J Formos Med Assoc | 2008 • Vol 107 • No 10
Partial trisomy 3p/monosomy 11q
Discussion We have presented a case of partial trisomy 3p/ monosomy 11q associated with striking prenatal sonographic findings of alobar HPE, orofacial clefts, pyelectasis and a unilateral duplex renal system. A case with a similar karyotype but different phenotype such as a Dandy-Walker variant and trigonocephaly has been reported.3 Partial trisomy 3p is known to be associated with HPE. However, HPE occurs in only 10% of the cases with partial trisomy 3p and patients with partial trisomy 3p seldom present major dysmorphic features.1,4 To date, at least 40 cases of distal 3p trisomy have been reported, and the clinical manifestations of distal 3p trisomy are variable.1 Smeets et al1 reported two cases with partial distal trisomy 3p, psychomotor retardation and mental retardation but without major dysmorphism and concluded that distal trisomy 3p is not associated with major dysmorphic signs and is not obviously recognizable as a syndrome. HPE is a developmental abnormality that is characterized by congenital malformations of the forebrain and mid-face. There are variable types of HPE, ranging from severe alobar HPE with cyclopia, ethmocephaly, cebocephaly, or HPEPMA, to microforms with microcephaly, corpus callosum agenesis/dysgenesis, mental retardation, ocular hypotelorism, or a single maxillary central incisor. Chromosomal aberrations, Mendelian mutations, and teratogens are known causes of HPE. HPE is associated with chromosomal abnormalities such as trisomy 13, trisomy 18, triploidy, del(2p), dup(3p), del(7q), del(13q), del(18p), and del(21q). Ming and Muenke5 suggested that HPE is caused by digenic inheritance and hypothesized that multiple genetic hits or environmental exposures may be required for the clinical expression of HPE. Simultaneous occurrence of dup(3p) and deletion of other chromosomal segments in patients with HPE have been reported. For instance, Buchinger et al6 reported a case of der(18)t(3;18) (p21;p11)mat with microcephaly, bilateral cleft lip and palate, a flat and retracted nose, and HPE-PMA. Martin and Steinberg7 described a case J Formos Med Assoc | 2008 • Vol 107 • No 10
of cebocephaly with der(4)t(3;4)(p25;q35)mat. Van Regemorter et al8 presented a case of HPEPMA with der(10)t(3;10)(p21;q26)mat. Gimelli et al9 reported a case of cyclopia with der(2)t(2;3) (p25;p23)mat. Gillerot et al10 reported a case of cyclopia with der(10)t(3;10)(p21;q26)pat. Chen et al11 reported two siblings of der(2)t(2;3)(q37; p21)pat, one with cyclopia and the other with HPE-PMA. Chen et al11,12 additionally reported a fetus of HPE-PMA with der(7)t(3;7)(p23;q36) de novo and a fetus of cyclopia with der(7)t(3;7) (p23;q36)pat. The present case provides evidence that partial trisomy 3p/monosomy 11q can be a genetic cause of HPE. The majority of affected cases with distal deletion of the long arm of chromosome 11 were reported in infancy and childhood. Prenatal diagnosis of distal del(11q) is rare. Chen et al2 reported the prenatal sonographic findings of a unilateral duplex renal system, pyelectasis and orofacial clefts at 20 weeks of gestation in a fetus with a karyotype of 46,XX,del(11)(q23). The present case demonstrates that a duplex renal system and pyelectasis associated with distal 11q monosomy can be diagnosed in utero in the early second trimester. Pyelectasis appears in 2–2.8% of normal pregnancies and is suggested as a sonographic marker for early identification of chromosomal abnormalities.13 A fetal duplex renal system occurs with an incidence of 0.048–0.06% in normal pregnancies, and can be associated with some chromosomal abnormalities such as dup(3)(q25qter), del(4)(q31qter), trisomy 8 mosaicism, del(11) (q23qter), Turner syndrome and dic(21)t(X;21) (p11.1;p11.1).2,14–16 The phenotype of the present case is the combinative effect of partial trisomy 3p and monosomy 11q. The reported cranial abnormalities associated with partial trisomy 3p included HPE, a dysplastic gyrus with heterotopic Purkinje cells in the cerebellar vermis, a midline structure in the area of the quadrigeminal plate corresponding to a plate cyst or a cavum vergae, microcephaly, arhinencephaly, congenital hypothalamic hamartoblastoma syndrome, a Dandy-Walker variant and the C (trigonocephaly) syndrome.3 Partial monosomy 11q is also 825
C.P. Chen, et al
characterized by renal abnormalities such as renal duplication and hydronephrosis.2 In summary, we demonstrated the prenatal sonographic identification of HPE, orofacial clefts, pyelectasis and a unilateral duplex renal system in a fetus with partial trisomy 3p and partial monosomy 11q. Complex malformations may be caused by multiple hits inherited from unbalanced familial translocations. Prenatal sonographic diagnosis of complex malformations should alert one to unbalanced chromosomal aberrations involving multiple chromosomal segments and prompt rapid cytogenetic analysis and genetic counseling.
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Acknowledgments This work was supported by research grants NSC96-2314-B-195-008-MY3 from the National Science Council and MMH-E-97004 from Mackay Memorial Hospital, Taipei, Taiwan.
References 1. Smeets E, Vandenbossche L, Fryns JP. Partial distal trisomy 3p. A partial autosomal trisomy without major dysmorphic features. Genet Counsel 2001;12:85–9. 2. Chen CP, Chern SR, Tzen CY, et al. Prenatal diagnosis of de novo distal 11q deletion associated with sonographic findings of unilateral duplex renal system, pyelectasis and orofacial clefts. Prenat Diagn 2001;21:317–20. 3. Chen CP, Tzen CY, Chang TY, et al. Prenatal diagnosis of partial trisomy 3p and partial monosomy 11q in a fetus
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with a Dandy-Walker variant and trigonocephaly. Prenat Diagn 2002;22:1112–3. Siebert JR, Cohen MM Jr, Sulik KK, et al. Holoprosencephaly: An Overview and Atlas of Cases. Wiley-Liss: New York, 1990:362. Ming JE, Muenke M. Multiple hits during early embryonic development: digenic diseases and holoprosencephaly. Am J Hum Genet 2002;71:1017–32. Buchinger G, Wettstein A, Metze H. Familial chromosome translocation t(3;18)(p21;p11). J Med Genet 1981;18: 119–23. Martin NJ, Steinberg BG. The dup(3p)(p25-pter) syndrome: a case with holoprosencephaly. Am J Med Genet 1983; 14:767–72. Van Regemorter N, Vamos E, Gillerot Y, et al. Partial trisomy 3p in two siblings: clinical and pathological findings. Eur J Pediatr 1983;141:53–6. Gimelli G, Cuoco C, Liturania M, et al. Dup(3)(p2-pter) in two families, including one infant with cyclopia. Am J Med Genet 1985;20:341–8. Gillerot Y, Hustin J, Koulischer L, et al. Prenatal diagnosis of a dup(3p) with holoprosencephaly. Am J Med Genet 1987;26:225–7. Chen CP, Liu FF, Jan SW, et al. Prenatal diagnosis of terminal deletion 7q and partial trisomy 3p in fetuses with holoprosencephaly. Clin Genet 1996;50:321–6. Chen CP, Devriendt K, Lee CC, et al. Prenatal diagnosis of partial trisomy 3p (3p23pter) and monosomy 7q (7q36qter) in a fetus with microcephaly, alobar holoprosencephaly and cyclopia. Prenat Diagn 1999;19:986–9. Kent A, Cox D, Downey P, et al. A study of mild fetal pyelectasia—outcome and proposed strategy of management. Prenat Diagn 2000;20:206–9. Livera LN, Brookfield DSK, Egginton JA, et al. Antenatal ultrasonography to detect renal abnormalities: a prospective screening programme. Br Med J 1989;298:1421–3. Schinzel A. Catalogue of Unbalanced Chromosome Aberrations in Man. Berlin: de Gruyter, 1983:432–3, 857. Vergani P, Ceruti P, Locatelli A, et al. Accuracy of prenatal ultrasonographic diagnosis of duplex renal system. J Ultrasound Med 1999;18:463–7.
J Formos Med Assoc | 2008 • Vol 107 • No 10
Prenatal Diagnosis of Partial Trisomy 3p (3p21pter) and Partial Monosomy 11q (11q23qter) Associated with Abnormal Sonographic Findings of Holoprosencephaly, Orofacial Clefts, Pyelectasis and a Unilateral Duplex Renal System Chih-Ping Chen,1,2,3,4* Tzu-Hao Wang,5 Chyi-Chyang Lin,6 Fuu-Jen Tsai,4,6 Lie-Jiau Hsieh,7 Wayseen Wang2,8 Patients with partial trisomy 3p seldom present major dysmorphic features, and holoprosencephaly occurs in only 10% of the cases with partial trisomy 3p. It has been suggested that multiple genetic hits or environmental exposures are required for the clinical expression of holoprosencephaly. At 16 weeks of gestation, prenatal sonography identified a fetus with holoprosencephaly, orofacial clefts, pyelectasis, and a unilateral duplex renal system. Amniocentesis revealed the karyotype of 46,XX,der(11)t(3;11)(p21;q23)pat with partial trisomy 3p (3p21pter) and partial monosomy 11q (11q23qter). The pregnancy was subsequently terminated. Postnatally, the proband showed hypotelorism, a depressed nasal bridge, orofacial clefts and holoprosencephaly-premaxillary agenesis. The present case provides evidence that partial trisomy 3p/ monosomy 11q can be a genetic cause of holoprosencephaly and del(11)(q23qter) is associated with a duplex renal system. [J Formos Med Assoc 2008;107(10):822–826] Key Words: duplex renal system, holoprosencephaly, orofacial clefts, partial monosomy 11q, partial trisomy 3p, pyelectasis
and hydronephrosis.1 Partial distal monosomy 11q is characterized by developmental delay, psychomotor retardation, craniofacial dysmorphism (trigonocephaly, hypertelorism, a broad and flat nasal bridge, a carp shaped mouth, a high arched palate, micrognathia, low-set malformed ears), congenital heart defects (ventricular septal defects, truncus arteriosus, aortic arch defects), renal anomalies (renal duplication, hydronephrosis),
Partial distal trisomy 3p is characterized by mental retardation and minor dysmorphism such as a square shaped face with full cheeks, hypertelorism, epicanthus, a thick and short nose, a prominent philtrum, full lips, a large mouth with downturned corners, micrognathia, and retrognathia. Partial distal trisomy 3p may occasionally be associated with major anomalies such as holoprosencephaly (HPE), facial clefts, cardiac anomalies,
©2008 Elsevier & Formosan Medical Association .
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Departments of 1Obstetrics and Gynecology, and 2Medical Research, Mackay Memorial Hospital, Taipei; 3Department of Biotechnology, Asia University, Taichung; 4School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung; 5Department of Obstetrics and Gynecology, Lin-Kou Medical Center, Chang-Gung Memorial Hospital, Chang-Gung University, Taoyuan; 6Department of Medical Genetics, China Medical University Hospital, Taichung; 7 Department of Life Sciences, Chung Shan Medical University, Taichung; and 8Department of Bioengineering, Tatung University, Taipei, Taiwan. Received: May 11, 2007 Revised: June 15, 2007 Accepted: August 7, 2007
822
*Correspondence to: Dr Chih-Ping Chen, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, 92, Section 2, Chung-Shan North Road, Taipei, Taiwan. E-mail: [email protected]
J Formos Med Assoc | 2008 • Vol 107 • No 10
Partial trisomy 3p/monosomy 11q
ocular malformations (ptosis, colobomas, cataracts, glaucoma, strabismus, telecanthus), limb anomalies (talipes equinovarus, clino- or camptodactyly, syndactyly), a short neck, widely spaced nipples, and thrombocytopenia or pancytopenia.2 Here, we present a rare case of prenatally detected partial trisomy 3p/monosomy 11q associated with striking abnormal sonographic findings.
Case Report A 30-year-old woman, gravida 4, para 2, was referred for genetic counseling at 16 weeks of gestation because of fetal anomalies on prenatal
ultrasound. The woman’s karyotype was 46,XX. Her husband was a carrier of a balanced reciprocal translocation and had a karyotype of 46,XY,t(3;11) (p21;q23). Four years previously, the woman gave birth to an abnormal fetus with multiple malformations including a Dandy-Walker variant and trigonocephaly, and a karyotype of 46,XX,der(11) t(3;11)(p21;q23)pat. During this pregnancy, level II sonograms at 16 weeks of gestation showed alobar HPE, orofacial clefts, pyelectasis and a left duplex renal system (Figure 1). Other biometric measurements were normal. Amniocentesis revealed a karyotype of 46,XY, der(11)t(3;11)(p21;q23)pat. Owing to an unbalanced segregation of the paternal t(3;11), the fetus
A
B
C
D
Figure 1. Prenatal ultrasound at 16 weeks of gestation shows: (A) alobar holoprosencephaly with the presence of a single ventricle and fused thalami; (B) left duplex renal system (arrows) with a dilated pelvis in the lower pole and pyelectasis of the right kidney (*); (C) orofacial clefts and facial dysmorphism; (D) Facial appearance at birth. J Formos Med Assoc | 2008 • Vol 107 • No 10
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C.P. Chen, et al
had two normal chromosomes 3, one normal chromosome 11, and one derivative chromosome 11, resulting in partial trisomy 3p (3p21pter) and partial monosomy 11q (11q23qter) (Figure 2). The derivative chromosome 11 was characterized by fluorescence in situ hybridization using the 3p/3q and 11p/11q specific subtelomeric probes (Vysis, Downers Grove, IL, USA) (Figures 3 and 4). The pregnancy was subsequently terminated, and a 100-g male fetus was delivered. At birth, the proband showed hypotelorism, a depressed nasal bridge, and orofacial clefts. Autopsy confirmed the diagnosis of HPE-premaxillary agenesis (HPE-PMA).
p21 Father q23
3
3
11
3
der(11)
11
Figure 2. Chromosome preparation shows the balanced reciprocal translocation identified in the father and chromosomes 3, 11 and der(11) in the proband. Arrows indicate the breakpoints.
B der(11)
der(11)
3
11
3
11
Figure 3. Fluorescence in situ hybridization study using 3p (green)/3q (red) TEL probes shows that der(11) is stained with a green signal by the 3p subtelomeric probe.
3
A
3
B 3
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der(11)
Proband
A
Figure 4. Fluorescence in situ hybridization study using 11p (green)/11q (red) TEL probes shows absence of a red signal by the 11q subtelomeric probe on der(11).
der(3)
3
3
der(11)
11
3
der(11)
11
J Formos Med Assoc | 2008 • Vol 107 • No 10
Partial trisomy 3p/monosomy 11q
Discussion We have presented a case of partial trisomy 3p/ monosomy 11q associated with striking prenatal sonographic findings of alobar HPE, orofacial clefts, pyelectasis and a unilateral duplex renal system. A case with a similar karyotype but different phenotype such as a Dandy-Walker variant and trigonocephaly has been reported.3 Partial trisomy 3p is known to be associated with HPE. However, HPE occurs in only 10% of the cases with partial trisomy 3p and patients with partial trisomy 3p seldom present major dysmorphic features.1,4 To date, at least 40 cases of distal 3p trisomy have been reported, and the clinical manifestations of distal 3p trisomy are variable.1 Smeets et al1 reported two cases with partial distal trisomy 3p, psychomotor retardation and mental retardation but without major dysmorphism and concluded that distal trisomy 3p is not associated with major dysmorphic signs and is not obviously recognizable as a syndrome. HPE is a developmental abnormality that is characterized by congenital malformations of the forebrain and mid-face. There are variable types of HPE, ranging from severe alobar HPE with cyclopia, ethmocephaly, cebocephaly, or HPEPMA, to microforms with microcephaly, corpus callosum agenesis/dysgenesis, mental retardation, ocular hypotelorism, or a single maxillary central incisor. Chromosomal aberrations, Mendelian mutations, and teratogens are known causes of HPE. HPE is associated with chromosomal abnormalities such as trisomy 13, trisomy 18, triploidy, del(2p), dup(3p), del(7q), del(13q), del(18p), and del(21q). Ming and Muenke5 suggested that HPE is caused by digenic inheritance and hypothesized that multiple genetic hits or environmental exposures may be required for the clinical expression of HPE. Simultaneous occurrence of dup(3p) and deletion of other chromosomal segments in patients with HPE have been reported. For instance, Buchinger et al6 reported a case of der(18)t(3;18) (p21;p11)mat with microcephaly, bilateral cleft lip and palate, a flat and retracted nose, and HPE-PMA. Martin and Steinberg7 described a case J Formos Med Assoc | 2008 • Vol 107 • No 10
of cebocephaly with der(4)t(3;4)(p25;q35)mat. Van Regemorter et al8 presented a case of HPEPMA with der(10)t(3;10)(p21;q26)mat. Gimelli et al9 reported a case of cyclopia with der(2)t(2;3) (p25;p23)mat. Gillerot et al10 reported a case of cyclopia with der(10)t(3;10)(p21;q26)pat. Chen et al11 reported two siblings of der(2)t(2;3)(q37; p21)pat, one with cyclopia and the other with HPE-PMA. Chen et al11,12 additionally reported a fetus of HPE-PMA with der(7)t(3;7)(p23;q36) de novo and a fetus of cyclopia with der(7)t(3;7) (p23;q36)pat. The present case provides evidence that partial trisomy 3p/monosomy 11q can be a genetic cause of HPE. The majority of affected cases with distal deletion of the long arm of chromosome 11 were reported in infancy and childhood. Prenatal diagnosis of distal del(11q) is rare. Chen et al2 reported the prenatal sonographic findings of a unilateral duplex renal system, pyelectasis and orofacial clefts at 20 weeks of gestation in a fetus with a karyotype of 46,XX,del(11)(q23). The present case demonstrates that a duplex renal system and pyelectasis associated with distal 11q monosomy can be diagnosed in utero in the early second trimester. Pyelectasis appears in 2–2.8% of normal pregnancies and is suggested as a sonographic marker for early identification of chromosomal abnormalities.13 A fetal duplex renal system occurs with an incidence of 0.048–0.06% in normal pregnancies, and can be associated with some chromosomal abnormalities such as dup(3)(q25qter), del(4)(q31qter), trisomy 8 mosaicism, del(11) (q23qter), Turner syndrome and dic(21)t(X;21) (p11.1;p11.1).2,14–16 The phenotype of the present case is the combinative effect of partial trisomy 3p and monosomy 11q. The reported cranial abnormalities associated with partial trisomy 3p included HPE, a dysplastic gyrus with heterotopic Purkinje cells in the cerebellar vermis, a midline structure in the area of the quadrigeminal plate corresponding to a plate cyst or a cavum vergae, microcephaly, arhinencephaly, congenital hypothalamic hamartoblastoma syndrome, a Dandy-Walker variant and the C (trigonocephaly) syndrome.3 Partial monosomy 11q is also 825
C.P. Chen, et al
characterized by renal abnormalities such as renal duplication and hydronephrosis.2 In summary, we demonstrated the prenatal sonographic identification of HPE, orofacial clefts, pyelectasis and a unilateral duplex renal system in a fetus with partial trisomy 3p and partial monosomy 11q. Complex malformations may be caused by multiple hits inherited from unbalanced familial translocations. Prenatal sonographic diagnosis of complex malformations should alert one to unbalanced chromosomal aberrations involving multiple chromosomal segments and prompt rapid cytogenetic analysis and genetic counseling.
4.
5.
6.
7.
8.
9.
Acknowledgments This work was supported by research grants NSC96-2314-B-195-008-MY3 from the National Science Council and MMH-E-97004 from Mackay Memorial Hospital, Taipei, Taiwan.
References 1. Smeets E, Vandenbossche L, Fryns JP. Partial distal trisomy 3p. A partial autosomal trisomy without major dysmorphic features. Genet Counsel 2001;12:85–9. 2. Chen CP, Chern SR, Tzen CY, et al. Prenatal diagnosis of de novo distal 11q deletion associated with sonographic findings of unilateral duplex renal system, pyelectasis and orofacial clefts. Prenat Diagn 2001;21:317–20. 3. Chen CP, Tzen CY, Chang TY, et al. Prenatal diagnosis of partial trisomy 3p and partial monosomy 11q in a fetus
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14.
15. 16.
with a Dandy-Walker variant and trigonocephaly. Prenat Diagn 2002;22:1112–3. Siebert JR, Cohen MM Jr, Sulik KK, et al. Holoprosencephaly: An Overview and Atlas of Cases. Wiley-Liss: New York, 1990:362. Ming JE, Muenke M. Multiple hits during early embryonic development: digenic diseases and holoprosencephaly. Am J Hum Genet 2002;71:1017–32. Buchinger G, Wettstein A, Metze H. Familial chromosome translocation t(3;18)(p21;p11). J Med Genet 1981;18: 119–23. Martin NJ, Steinberg BG. The dup(3p)(p25-pter) syndrome: a case with holoprosencephaly. Am J Med Genet 1983; 14:767–72. Van Regemorter N, Vamos E, Gillerot Y, et al. Partial trisomy 3p in two siblings: clinical and pathological findings. Eur J Pediatr 1983;141:53–6. Gimelli G, Cuoco C, Liturania M, et al. Dup(3)(p2-pter) in two families, including one infant with cyclopia. Am J Med Genet 1985;20:341–8. Gillerot Y, Hustin J, Koulischer L, et al. Prenatal diagnosis of a dup(3p) with holoprosencephaly. Am J Med Genet 1987;26:225–7. Chen CP, Liu FF, Jan SW, et al. Prenatal diagnosis of terminal deletion 7q and partial trisomy 3p in fetuses with holoprosencephaly. Clin Genet 1996;50:321–6. Chen CP, Devriendt K, Lee CC, et al. Prenatal diagnosis of partial trisomy 3p (3p23pter) and monosomy 7q (7q36qter) in a fetus with microcephaly, alobar holoprosencephaly and cyclopia. Prenat Diagn 1999;19:986–9. Kent A, Cox D, Downey P, et al. A study of mild fetal pyelectasia—outcome and proposed strategy of management. Prenat Diagn 2000;20:206–9. Livera LN, Brookfield DSK, Egginton JA, et al. Antenatal ultrasonography to detect renal abnormalities: a prospective screening programme. Br Med J 1989;298:1421–3. Schinzel A. Catalogue of Unbalanced Chromosome Aberrations in Man. Berlin: de Gruyter, 1983:432–3, 857. Vergani P, Ceruti P, Locatelli A, et al. Accuracy of prenatal ultrasonographic diagnosis of duplex renal system. J Ultrasound Med 1999;18:463–7.
J Formos Med Assoc | 2008 • Vol 107 • No 10