Clinical Vignette

1 Abstract

Complete or partial trisomy 10q involves a duplication of the long arm of chromosome 10. Distal 10q trisomy is a well-recognized but rare genetic syndrome in which duplication of distal segments of 10q results in a pattern of malformations. Molecular cytogenetic techniques are advantageous not only in identifying submicroscopic chromosomal imbalances, but also in identifying the exact origin of the extra chromosomal material. Many a times, the phenotype of patients also evolves with age. We report a 17-year-old boy, suspected to have Trisomy 21 during infancy, but who on re-evaluation and follow up, was identified by cytogenetic microarray (CMA) to have partial 10q duplication. In this short report, we discuss the overlapping features of 10q duplication with trisomy 21 and utility of CMA in evaluation of chromosomal imbalances.

2 Introduction

Duplication of 10q was first reported by Klep-de Pater et al. (1979) as a recognizable syndrome. It is characterized by a high and large forehead, round and flat face with flat nasal bridge, epicanthic folds, hypertelorism, fine eyebrows, antimongoloid slant of eyes, low-set ears, cleft palate, micrognathia, short nose, bow-shaped mouth, microcephaly, hypotonia, joint laxity, clinodactyly, scoliosis, short neck, growth retardation, psychomotor disorders, and cardiac, ocular and renal abnormalities (Roux et al., 1974; Berger et al., 1976; Tomkins et al., 1983; Klep-de Pater et al., 1979; Davies et al., 1998). The evidence for a distal 10q duplication syndrome is limited by the fact that out of well over 50 cases reported, no more than a handful have only 10q duplication without involvement of any other chromosome arm (Sarri et al., 2011; Carter et al., 2010; Xiao et al., 2012). With the advent of molecular cytogenetic techniques, it is possible to better delineate the region involved in the 10q duplication and also to detect other co-existing chromosomal imbalances.

Here we report a 17-years-old propositus with dysmorphic features and developmental delay with 10q duplication.

3 Case report

A 17-year-old boy, born to healthy and non-consanguineous parents was first evaluated at 14 days of life for dysmorphic features. His facial features at that time were suggestive of Down syndrome and a karyotype was performed, which showed extra material on the q arm of chromosome 10 (Figure 1). Due to phenotypic resemblance to Down syndrome, a diagnosis of trisomy 21 was given and it was concluded that the extra material on chromosome 10q was a translocated long arm of chromosome 21 (21q). Parents’ karyotypes were normal. The family was accordingly counseled and thereafter the child was lost to follow up.

He was brought to the Genetics OPD again, after 17 years, for evaluation of global developmental delay, delayed puberty and facial dysmorphism. On examination his height was 172 cm (+1.5 to +2 SD), weight was 75 kg (+1.5 to +2 SD) and head circumference was 53.5cm (-2 SD). He had an oval, flat face with a protruding thick lower lip, mid face hypoplasia, short nose, a short neck, low posterior hair line, small ears, micropenis and delayed puberty (SMR stage 2) and this time his facial features were not suggestive of Down syndrome (Figure 2). He had bilateral simian crease and difficulty in squatting. He did not have ptosis but had puffy upper eyelids bilaterally. He was found to have slipped epiphyses of head of femur. There was no history of seizures, gastrointestinal symptoms, cardiac symptoms or frequent infections. He was studying in the 9^th standard and had learning difficulties. Formal evaluation showed IQ to be 65 (by Malin’s intelligence scale for Indian children). Cytogenetic microarray was performed to ascertain the origin of extra material on chromosome 10.

Cytogenetic Microarray done using Affymetrix CytoScan™ 750K Array revealed a 23.5Mb duplication of 10q25.1 (arr[hg19] 10q25.1q26.3(109,292,821-132,860,709)x3) and a terminal 2.5Mb deletion of 10q26.3 (arr[hg19] 10q26.3(132,861,927-135,426,386)x1) (Figure 3).

4 Discussion

This case illustrates the utility of CMA in delineating imbalances detected by traditional karyotyping. The case also stresses the need to re-evaluate patients with undiagnosed dysmorphic syndromes using newer diagnostic tests. Table 1 summarizes clinical features of cases with duplication of terminal part of q arm of chromosome 10. Majority of the reported cases have occurred in association with partial monosomy of other chromosomes, complicating the delineation of clinical features.