17q23.2q23.3 de novo duplication in association with speech and language disorder, learning difficulties, incoordination, motor skill impairment, and behavioral disturbances: a case report

• Published in: BMC medical genetics 2017-10, Vol.18 (1), p.119-119, Article 119
• Main Authors: Wessel, Karen, Suleiman, Jehan, Khalaf, Tamam E, Kishore, Shivendra, Rolfs, Arndt, El-Hattab, Ayman W
• Format: Article
• Language: English
• Subjects: 17q23.2q23.3 duplication; Age; Ankyrins; Ataxia - diagnosis; Ataxia - genetics; Ataxia - physiopathology; Behavior; Brain injury; Case Report; Case reports; Case studies; Child; Chromosomal disorders; Chromosomal microarray; Chromosome 17; Chromosome abnormalities; Chromosome Duplication; Chromosome rearrangements; Chromosomes; Chromosomes, Human, Pair 17 - chemistry; Clubfoot; Congenital diseases; Developmental Disabilities - diagnosis; Developmental Disabilities - genetics; Developmental Disabilities - physiopathology; Diagnosis; Diagnostic tests; DNA microarrays; EEG; Electroencephalography; Foot diseases; Gene Dosage; Gene duplication; Gene Expression; Gene mutation; Genes; Genomes; Genomic rearrangements; Growth rate; Humans; Hyperactivity; Intellectual disabilities; Learning disabilities; Learning Disorders - diagnosis; Learning Disorders - genetics; Learning Disorders - physiopathology; Male; Motor skill learning; Mutation; Phenotype; Phenotypes; Proteins - genetics; Psychomotor Disorders - diagnosis; Psychomotor Disorders - genetics; Psychomotor Disorders - physiopathology; Seizures; Seizures - diagnosis; Seizures - genetics; Seizures - physiopathology; Self-Injurious Behavior - diagnosis; Self-Injurious Behavior - genetics; Self-Injurious Behavior - physiopathology; Skills; Speech; Speech Disorders - diagnosis; Speech Disorders - genetics; Speech Disorders - physiopathology
• ISSN: 1471-2350; 1471-2350
• DOI: 10.1186/s12881-017-0479-3

Chromosomal rearrangements involving 17q23 have been described rarely. Deletions at 17q23.1q23.2 have been reported in individuals with developmental delay and growth retardation, whereas duplications at 17q23.1q23.2 appear to segregate with clubfoot. Dosage alterations in the TBX2 and TBX4 genes, located in 17q23.2, have been proposed to be responsible for the phenotypes observed in individuals with 17q23.1q23.2 deletions and duplications. In this report, we present the clinical phenotype of a child with a previously unreported de novo duplication at 17q23.2q23.3 located distal to the TBX2 and TBX4 region. We report a 7.5-year-old boy with speech and language disorder, learning difficulties, incoordination, fine motor skill impairment, infrequent seizures with abnormal EEG, and behavior disturbances (mild self-inflicted injuries, hyperactivity-inattention, and stereotyped hand movements). Chromosomal microarray revealed a 2-Mb duplication of chromosome 17q23.2q23.3. Both parents did not have the duplication indicating that this duplication is de novo in the child. The duplicated region encompasses 16 genes. It is possible that increased dosage of one or more genes in this region is responsible for the observed phenotype. The TANC2 gene is one of the genes in the duplicated region.It encodes a member of the TANC (tetratricopeptide repeat, ankyrin repeat and coiled-coil containing) family which includes TANC1 and TANC2. These proteins are highly expressed in brain and play major roles in synapsis regulation. Hence, it is suggestive that TANC2 is the likely candidate gene responsible for the observed phenotype as an increased TANC2 dosage can potentially alter synapsis, resulting in neuronal dysfunction and the neurobehavioral phenotype observed in this child with 17q23.2q23.3 duplication.