Chromosome 10Q Deletion Del (10)(Q26.1Q26.3) Is Associated with Cataract

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provided by Elsevier - Publisher Connector Pediatrics and Neonatology (2013) 54, 132e136

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CASE REPORT Chromosome 10q Deletion del (10)(q26.1q26.3) is Associated with Cataract

Yu-Tzu Chang a,b, I-Ching Chou a,c, Chung-Hsing Wang d,e, Zheng-Nan Chin a, Huang-Tsung Kuo a,f, Chyi-Chyang Lin g, Chang-Hai Tsai a,h, Fuu-Jen Tsai d,i,j,k,*

a Division of Pediatric Neurology, Children’s Medical Center, China Medical University Hospital, Taichung, Taiwan b China Medical University, Taichung, Taiwan c Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan d Division of Pediatric Genetics and Metabolism, Children’s Medical Center, Taichung, Taiwan e Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan f Division of Children’s Development and Behavior, Children’s Medical Center, China Medical University Hospital, Taichung, Taiwan g Department of Medical Research, China Medical University Hospital, Taichung, Taiwan h Department of Healthcare Administration, Asia University, Taichung, Taiwan i School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan j College of Health Science, Asia University, Taichung, Taiwan k Department of Medical Genetics, China Medical University and Hospital, Taichung, Taiwan

Received Jun 10, 2011; received in revised form Jan 17, 2012; accepted Jan 30, 2012

Key Words Distal 10q deletion syndrome is an uncommon chromosomal disorder. Interstitial deletion cataract; involving bands 10q25e10q26.1 is extremely rare and few cases have been reported. The char- chromosome 10; acteristic features are facial dysmorphisms, postnatal growth retardation, developmental interstitial deletion delay, congenital heart disease, genitourinary anomalies, digital anomalies, and strabismus. We report for the ﬁrst time a patient with de novo 10q interstitial deletion del (10)(q26.1q26.3) and cataract. Copyright ª 2012, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved.

* Corresponding author. Number 2, Yuh-Der Road, North District, Taichung 40447, Taiwan. E-mail address: [email protected] (F.-J. Tsai).

1875-9572/$36 Copyright ª 2012, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. All rights reserved. http://dx.doi.org/10.1016/j.pedneo.2012.10.010 Deletion of chromosome 10q with cataract 133

1. Introduction arteriosus, and severe pulmonary artery hypertension was found soon after birth. Total surgical repair was performed Patients with terminal deletion of the long arm of chro- at 7 months. Evoked-response audiometry revealed a left mosome 10 present with phenotypic manifestations, sensorineural hearing impairment (hearing loss: left: including facial dysmorphisms, postnatal growth retarda- 65 dB). Development has shown a global delay. She first sat tion, developmental delay, mental retardation, digital at 14 months, crawled at 20 months, stood at 24 months, anomalies, cardiac defects, and genitourinary defects.1,2 It and began walking alone at 29 months of age. Her first is an uncommon chromosomal disorder, with most terminal meaningful words were spoken at 5 years of age and speech deletions starting at breakpoints in bands 10q25 or 10q26. delay has been noted since, limited to a few words. In contrast to these terminal deletions, interstitial dele- Furthermore, verbal comprehension is limited to common tions within bands 10q25e10q26.3 are extremely rare and verbal instructions. Growth delay was also noted at 6 < rd only seven cases have been reported.3 However, it is months old, her height was 54.8 cm ( 3 percentile) and < rd unknown whether the phenotypes are different from her weight was 3.8 kg ( 3 percentile). Global develop- terminal deletions. Here, we report the first reported case ment assessment at 8 years and 10 months showed with a de novo 10q interstitial deletion, del a developmental quotient (DQ) of 36. Cranio-cerebral (10)(q26.1q26.3). In addition to many of the phenotypic magnetic resonance imaging (MRI) was normal. Renal anomalies previously described in interstitial 10q cases, our sonography revealed bilateral kidney hypotrophy with no patient presented with cataracts. other urogenital defects. The patient is now 10 years and 5 < rd It is estimated that there are 1.5 million blind children in months old. Her height is 103.5 cm ( 3 percentile) and < rd the world.4 Cataract is the main cause of treatable blind- her weight is 14.5 kg ( 3 percentile). ness in children. Information on the ocular and systemic Eye examination revealed a cataract on the left side at 7 characteristics of pediatric cataract syndromes is useful for years of age, which was the reason for the first visit to our further systemic screening needs and genetic evaluation. hospital. The left retina was normal and there was no strabismus. Chromosome preparation of peripheral white blood cells 2. Case Report was performed, and trypsin-banding Giemsa was applied at 550 band resolution. G-banding analysis revealed that the The patient, a 10.5-year-old girl, is the first child of patient had a karyotype of 46, xx, del (10) (q26.1q26.3) healthy, unrelated parents. She was born spontaneously at (Figure 2). In order to rule out familial translocation, 36 weeks with uncomplicated pregnancy. Her birth body parental blood samples were also analyzed and found to be weight was 2.25 kg (25th percentile). She had a triangular normal. These results indicated that the chromosomal and asymmetric face, prominent nasal bridge, hyper- aberration was de novo in origin. An additional study with telorism, malformed ears, right ear skin tag, simian crease, fluorescence in situ hybridization (FISH) was performed and bilateral clinodactyly (Figure 1A and B). Congenital (Figure 3). A single whole-chromosome painting probe heart disease with ventricular septal defect, patent ductus specific for chromosome 10 (CPMC-GM10926) was employed

Figure 1 Gross appearance and face of this case. Note the triangular and asymmetric face, prominent nasal bridge, hypertelorism and malformed ear. 134 Y.-T. Chang et al

del(10q). Therefore, we considered that the deletion was interstitial with the karyotype of the patient, designated as 46,XX, del(10)(q26.1q26.3).5

3. Discussion

The existence of a 10q-syndrome was suggested previously by Wulfsberg et al,6 who reviewed 18 cases of terminal 10q deletions. Despite the variation of symptoms, some features are consistently seen, such as facial dysmorphisms charac- terized by a broad nasal bridge with beaked or prominent noses, strabismus, malformed and low-set ears, hyper- Figure 2 Partial karyotyping from the patient’s peripheral telorism and facial asymmetry. Other common features are leukocytes showing 10q26.1eq26.3 deletion. growth retardation, psychomotor delay, learning disabilities, cryptorchidism in males, genital defects, and digital anomalies such as clinodactly and syndactly. The majority of to further rule out microtranslocation. The FISH result distal 10q deletions include the terminal region, and reports clearly showed that both the normal chromosome 10 and of patients with interstitial deletions involving band the deleted chromosome 10 were painted and no other 10q25eq26.3 are rare. De novo interstitial deletions of 10q painting signal was detected in other chromosomes, indi- are very rare with only a few reported cases. To date, only cating that no other chromosome was involved. Further seven patients have been described with interstitial dele- FISH studies were performed to delineate the 10q26 tions involving band 10q25 and/or q26.3.1,3,7,8 A summary of terminal deletion. A ToTelVysis # 10 subtelomeric probe set the clinical features of 35 previously reported del 10q26 (spectrumgreen labeled 10pt, spectrumorange labeled cases is presented in Table 1 with comparison to our case 10qt, and spectrumgreen and spectrumorange labeled observations.2,6,9e21 Clinical manifestations of patients with 15qt) and biotinylated telomere (TTAGGG)n probe were interstitial deletions involving chromosome bands used to study the 10q26 terminal deletion. 10q25.2e10q26.3 are also summarized in Table 1. The FISH result of the ToTelVysis # 10 subtelomeric Some, but not all, clinical features frequently associated probe set showed that the 10qt subtelomeric probe (green with terminal 10q have also been reported in patients with signal) was only presented on one 10qt of chromosome 10 interstitial deletions. Psychomotor delay, speech delay, homologs in 50 examined metaphase cells (Figure 4A). The motor delay, and learning disabilities were noted in cases FISH result of the biotinylated telomere (TTAGGG)n probe with deletions near 10q26 (30/34 cases or 88%) and with revealed that all telomeric regions had FISH signals (red interstitial deletions (5/7 or 71%). In our case, develop- signal) in the 56 metaphase cells examined (Figure 4B). mental assessment at 8 years and 10 months revealed Therefore, the FISH results suggested that this patient had a moderate delay (DQ of 36). Global delay was noted in a 10q terminal deletion from 10q26.1 to the subtelomeric both groups. Growth retardation was noted in our case, as region, while the universal telomeric sequences existed on the patient’s height and weight were <3rd percentile. the terminal of del(10q) to stabilize the chromosome end of Other manifestations, such as prominent nose, broad nasal bridge, large or malformed ears, cryptorchidism, and joint abnormalities were also noted in both interstitial and terminal deletion groups. Facial asymmetry, strabismus, and sensorineural hearing loss were different, however (Table 1). Facial asymmetry was seen in only two cases (including ours) associated with interstitial deletion, although the number of 10q cases is limited. Patients with 10q deletions at a break site near 10q25 appear to have a higher frequency of severe congenital hearing anomalies, anogenital anomalies, and urinary tract anomalies, than those with a break site at 10q26.2,10 Waggoner et al10 concluded that in patients with break sites at 10q25, 71% (5 out of 7) had congenital hearing disease (CHD).10 Some patients with terminal deletion of chromosome 10q were found to suffer from sex reversal or ambiguous genitalia.6,17 Cryptorchidism has been reported in male patients, in addition to genital anomalies such as small scrotum and penis,14,15,22,23 while females present with hypoplastic external genitalia.9,24 However, there was no external Figure 3 De novo 10q26.1eq26.3 deletion with no micro- genital anomaly in our case. Strabismus was observed in 18 translocation. Fluorescence in situ hybridization with a single out of 27 terminal deletion cases (67%), but our patient whole-chromosome painting probe speciﬁc for chromosome 10 presented with a cataract on the left side without demonstrated the deletion. strabismus. Deletion of chromosome 10q with cataract 135

Figure 4 FISH analysis with a subtelomeric probe set and biotinylated telomere probe to study the 10q26 terminal deletion. (A) The FISH result from a subtelomeric probe set showed that the 10qt subtelomeric probe (green signal) was only presented on one 10qt of chromosome 10 homologs. (B) The biotinylated telomere probe revealed that all telomeric regions have FISH signals (red signal). Therefore, the FISH results suggested that this patient has a deletion of 10q from 10q26.1 to the subtelomeric region, while the universal telomeric sequences exist on the terminal of del(10q). FISH Z ﬂuorescence in situ hybridization.

Several defects had been reported to be associated with defects.8 The b-tectorin gene, together with a-tectorin gene mutations/deletions within 10q, such as ectrodactyly gene, encodes the major noncollagenous proteins of the (split hand/split foot malformation) at locus 10q24e10q25.25 tectorial membrane of the cochlea. Three of the patients, In addition, multiple mutations in the ﬁbroblast growth including our case, with interstitial 10q25e26.1 deletions factor receptor 2 gene (also in this region) have been asso- had temporary sensorineural and mild hearing loss (Table ciated with craniosynostosis syndromes.26,27 1),1 which might be associated with b-tectorin haplo A multiple gene locus study of 10q reported multiple insufﬁciency. Deletions of ADRA2A, the gene encoding the defects. For example, the ADRB1 gene encoding the b1 a2A adrenergic receptor, might be related to learning adrenergic receptor may be associated with cardiac disabilities.8 Curiously, however, cataracts have never been

Table 1 Clinical features present with interstitial deletions. del (10)q26 except Interstitial deletion Our case interstitial type* (%) 10q25.2-10q26.3y (%) Low birth weight <3% 8/32z (25%) 2/7 (29%) þ Short stature (<3rd percentile) 22/33z (67%) 2/7 (29%) þ Psychomotor retardation 30/34z (88%) 5/7 (71%) þ Asymmetric face 17/31z (55%) 1/7 (14%) þ Hypertelorism 11/30z (37%) 5/7 (71%) þ Cataract 0/35 (0%) 0/7 (0%) þ Strabismus 18/27z (67%) 2/7 (29%) d Downward slanting palpebral fissures 5/28z (18%) 2/7 (29%) d Prominent nose, broad nasal bridge 26/34z (76%) 6/7 (86%) þ Large, malformed, low-set ears 21/32z (66%) 4/7 (57%) Right ear skin tag Genital defect 11/27z (41%) 2/7 (29%) d Cryptorchidism 10/14 males (71%) 1/2 males (50%) d Urinary tract anomaly 7/35 (20%) 0/7 (0%) Small kidney Congenital heart disease 9/35 (26%) 1/7 (14%) þ Sensorineural hearing loss 1/19z (5%) 2/7 (29%) þ(Left) Joint abnormality 15/35 (43%) 3/7 (43%) þ Syndactyly (2nd and 3rd toe or 4th and 5th toe) 6/30z (20%) 1/7 (14%) d Clinodactyly 10/21z (48%) 2/7 (29%) þ Simian crease 3/35 (9%) 0/7 (0%) þ * Summary of the clinical features in 35 previously published cases of del 10q26.2,6,19,26 y Clinical features of seven patients with interstitial deletions involving chromosome bands 10q25.2-10q26.3. z Features scored only for patients where specific information was available. 136 Y.-T. Chang et al reported in 10q deletion cases. In children with cataracts, 7. McCandless SE, Schwartz S, Morrison S, Garlapati K, Robin NH. the etiology may be inherited, stem from a metabolic Adult with an interstitial deletion of chromosome 10 disease, or be associated with systemic abnormalities, but [del(10)(q25. 1q25.3)]: overlap with Coffin-Lowry syndrome. e in most cases, the etiology is unclear. In older children, Am J Med Genet 2000;95:93 8. cataracts are often related to injuries or ocular inflamma- 8. Kehrer-Sawatzki H, Daumiller E, Mu¨ller-Navia J, Kendziorra H, Rossier E, du Bois G, et al. Interstitial deletion tion related to juvenile rheumatoid arthritis. However, in del(10)(q25.2q25.3 approximately 26.11)dcase report and our case, there was no trauma history or ocular inflamma- review of the literature. Prenat Diagn 2005;25:954e9. tory disease. There was also no metabolic disease in our 9. Schrander-Stumpel C, Fryns JP, Hamers G. The partial mono- patient. There are many systemic disorders including somy 10q syndrome: report on two patients and review of the inherited diseases which are associated with pediatric developmental data. J Ment Defic Res 1991;35:259e67. cataract, including abnormal gene locus at 10q.28,29 In 10. Waggoner DJ, Chow CK, Dowton SB, Watson MS. Partial 1997, Narahara et al29 reported that the PAX2 gene asso- monosomy of distal 10q: three new cases and a review. Am J ciated with optic nerve coloboma-renal disease was linked Med Genet 1999;86:1e5. to 10q25.2, suggesting that the PAX2 gene may play a role in 11. Turleau C, de Grouchy J, Ponsot G, Bouygues D. Monosomy e the observed optic defects (such as strabismus or cata- 10qter. Hum Genet 1979;47:233 7. 12. Taysi K, Strauss AW, Yang V, Padmalatha C, Marshall RE. 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Deletions of the long arm of chromosome 10. e of the deletion and whether the phenotypic manifestations Am J Med Genet 1985;20:181 96. 16. Teyssier M, Charrin C, Dutruge J, Rousselle C. Monosomy differ between interstitial and terminal deletions. 10qter: a new case. J Med Genet 1992;29:342e3. Concerning the study limitations, we still cannot exclude 17. Wilkie AO, Campbell FM, Daubeney P, Grant DB, Daniels RJ, the possibility of there being no causal relationship Mullarkey M, et al. Complete and partial XY sex reversal between the cataract and the 10q deletion. Based on this associated with terminal deletion of 10q: report of 2 cases and observation, however, we suggest that evaluation of eye literature review. Am J Med Genet 1993;46:597e600. status is still required for any individuals with this genetic 18. Petit P, Devriendt K, Azou M, Gewillig M, Fryns JP. Terminal condition. 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