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Clinical Vignette
| Devriendt et al. (1999) | Hou (2003) | Migliori et al. (2002) | Petek et al. (2001) | Al-Sarraj et al. 2014 | Wong et al. 2015 | Carter et al. 2010 | Sarri et al. 2011 | Xiao et al. 2012 | Present study |
Cytogenetic technique | FISH | FISH | FISH | FISH | CMA | CMA | CMA | CMA | CMA | CMA |
Segment
| ||||||||||
Duplication | 10q26-qter | 10q26.1-qter | 10q25.3-qter | 10q24.33-qter | 10q24.31-10qter | 10q23.1-10q25.1 | 10q25.1-26.3 | 10q26.11-q26.2 | 10q25.3-26.2 | 10q25.1-26.3 |
Deletion | - | - | - | - | - | - | 10q26.3-qter | 10q26.22-q26.3 | 10q26.2-26.3 | 10q26.3 |
Development
| ||||||||||
Mental retardation/ Developmental delay | + | + | + | + | + | + | + | + | + | + |
Short stature | - | - | - | + | + | + | + | + | - | - |
Facial dysmorphisms
| ||||||||||
Blepharophimosis | + | + | + | + | + | - | + | - | + | - |
Hypertelorism/ epicanthus | - | - | + | + | + | + | + | + | + | - |
Ptosis | - | - | + | - | - | + | + | - | - | - |
Low-set/ malformed ears | - | - | + | + | - | - | + | - | + | + |
Strabismus | - | - | - | - | + | - | - | + | + | - |
Short neck | - | + | + | - | - | + | + | + | + | + |
Long philtrum | - | + | - | + | + | - | - | - | + | - |
Skeletal anomalies
| ||||||||||
Camptodactyly/ sandal gap | + | + | + | - | + | + | + | + | - | - |
Lordosis/scoliosis | + | + | - | - | + | + | + | - | - | - |
Hypermobility | + | + | + | + | - | - | + | - | - | - |
Hip dysplasia | - | - | - | + | - | - | + | - | - | + |
Hypotonia | + | - | + | + | - | - | + | + | + | - |
Others | - | Hearing loss; ventricular septal defect | - | - | Facial asymmetry, marfanoid habitus, autism | Left-sided inguinal hernia, cardiac, renal, ocular and brain abnormalities, autism | Hearing loss | Behavioral anomalies | - | Bilateral simian crease, difficulty in squatting, delayed puberty, Down syndrome like features in early infancy |
Our literature search yielded nine case reports with sufficient clinical data to attempt a comparison of features by size of duplicated segment (Figure 4 and Table 1). The comparison is limited by the resolution of the breakpoint mapping in older reports, as only few of them were subjected to microarray analysis. Four cases were evaluated by traditional karyotyping and FISH and five were evaluated by CMA. Only three cases are reported where duplication of 10q is associated with deletion (Sarri et al 2011, Carter et al 2011, Xiao et al 2012). In our study, the patient had a de novo duplication of 10q25.1–q26.3 spanning 23.5Mb, arr[hg19] 10q25.1q26.3(109,292,821-132,860,709)x3 which contains approximately 84 known genes, as well as a 2.5Mb deletion of the terminal end of 10q26.3arr[hg19] 10q26.3(132,861,927-135,426,386)x1 including 16 OMIM genes.
Though the patient was clinically suspected to have Down syndrome in the neonatal period, on re-evaluation at 17 years of age his phenotype had evolved clearly and did not match the Down syndrome phenotype. Oval face, small nose, midface hypoplasia, protruding and thick lower lip, low posterior hair line and puffy eyelids were the conspicuous features of this patient. Similar facial phenotype has been described in other reports (Migliori et al., 2002; Al-Saraj et al., 2014). All the reported cases had a variable degree of intellectual disability; the reported patient had moderate intellectual disability. Most of the reported cases had blepharophimosis and ptosis, hypotonia, hypermobility, mild hand and foot anomalies, and absence of major congenital anomalies (Miglior et al., 2002; Carter et al., 2010). The smallest involved region was from 10q26.2-qter (Devriendt et al., 1999), suggesting that a dosage-sensitive locus responsible for blepharophimosis in these individuals resides within band 10q26.2 or 10q26.3. Two of the reported cases had conductive hearing loss (Hou et al., 2003; Carter et al., 2010) and two had autism (Al-Saraj et al., 2014, Wong et al., 2015). Phenotypic features of cases of 10q duplication (only) and cases with duplication followed by terminal deletion of 10q are given in Table 1. Blepharophimosis had once been considered as a characteristic feature for 10q duplication but it is not present in all the cases including the present case. Additional frequent features of 10q duplication are skeletal anomalies, which include camptodactyly, sandal gap, scoliosis or hypermobility as listed in Table 1. Our patient had no obviously abnormal skeletal feature but on radiological evaluation was found to have slipped epiphyses of head of the femur.
This case report clearly reinforces the fact that it is important to review patients with dysmorphic syndromes and keep them under regular follow-up, as both the clinical phenotype and diagnostic technologies evolve with time.
We sincerely thank the cooperation of the patient and his family and acknowledge Indian Council of Medical Research, New Delhi for funding (BMS- 63/8/2010).
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