Down syndrome phenotype in a boy with a mosaic microduplication of chromosome 21q22

Franziska Schnabel,Silke Pauli,Peter Burfeind,Iris Bartels,Mateja Smogavec,Rudolf Funke

doi:10.1186/s13039-018-0410-4

Abstract

BackgroundDown syndrome, typically caused by trisomy 21, may also be associated by duplications of the Down syndrome critical region (DSCR) on chromosome 21q22. However, patients with small duplications of DSCR without accompanying deletions have rarely been reported.Case presentationHere we report a 5½-year-old boy with clinical features of Down syndrome including distinct craniofacial dysmorphism and sandal gaps as well as developmental delay. Conventional karyotype was normal, whereas interphase FISH analysis revealed three signals for DSCR in approximately 40% of lymphocytes and 80% of buccal mucosa cells. Array-CGH analysis confirmed a 2.56 Mb duplication of chromosome 21q22.13q22.2 encompassing DYRK1A.ConclusionThis presents one of the smallest duplications within DSCR leading to a Down syndrome phenotype. Since the dosage sensitive gene DYRK1A is the only duplicated candidate DSCR gene in our patient, this finding supports the hypothesis that DYRK1A contributes to dysmorphic and intellectual features of Down syndrome even in a mosaic state.

Highlights

Down syndrome, typically caused by trisomy 21, may be associated by duplications of the Down syndrome critical region (DSCR) on chromosome 21q22
Array-Comparative genome hybridization (CGH) analysis confirmed a 2.56 Mb duplication of chromosome 21q22.13q22.2 encompassing Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1A (DYRK1A). This presents one of the smallest duplications within DSCR leading to a Down syndrome phenotype
Interphase fluorescence in situ hybridization (FISH) revealed a mosaic pattern with three signals for DSCR in approximately 40% of lymphocytes and in approximately 80% of buccal mucosa cells (Fig. 1c)

Summary

Introduction

Typically caused by trisomy 21, may be associated by duplications of the Down syndrome critical region (DSCR) on chromosome 21q22. Case presentation: Here we report a 51⁄2-year-old boy with clinical features of Down syndrome including distinct craniofacial dysmorphism and sandal gaps as well as developmental delay. Down syndrome (DS), typically caused by complete trisomy 21, is associated with a wide range of clinical phenotypes including cognitive deficits, craniofacial dysmorphism, neurological, cardiovascular, immunological defects as well as ophthalmologic and hearing problems. It has been known for decades that not the complete duplicated chromosomal region in trisomy 21 patients contributes to the DS phenotype. Genotype-phenotype studies on partial trisomies performed by Sinet et al [1] revealed that the genes which are essential in producing the main DS features cluster within a relatively small region in chromosomal bands 21q22.2q22.3. Until the year 2000, the technical options to establish a genotype-phenotype correlation

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