8q22.2q22.3 Microdeletion Syndrome Associated with Hearing Loss and Intractable Epilepsy

Abstract

8q22.2q22.3 microdeletion syndrome has been described in only seven patients. We present a new case from Colombia. The characteristics of this condition are developmental delay, microcephaly, seizures, and typical facial dysmorphism. We discuss the clinical phenotype of the patient presenting relevant findings like hearing loss and severe epilepsy and the possible relations between the phenotype and the genes involved in the microdeletion. We describe a female with developmental delay, microcephaly, epilepsy, severe short stature, impaired speech, facial dysmorphism, and congenital deafness. A minimal/maximal deletion of 5.238 Mb and 5.374Mb, respectively, at 8q22.2q22.3 was diagnosed using a genome-wide array. The clinical phenotype is similar to the others seven patients previously reported; however, the severity of epilepsy and the concomitant hearing loss is remarkable, characteristics previously observed independently in only two patients. The KCNS2 gene is located in the deleted regions (8q22.2). Therefore it is a possible candidate for explaining the complex neurologic phenotype.

Universal chromosomal microarray analysis reveals high proportion of copy‐number variants in low‐risk pregnancies

“…Four of the pathogenic CNVs were > 10 Mbp and could presumably have been detected by traditional karyotyping, leaving 23 (0.36%) of low-risk cases with a CNV that would not have been detected by karyotyping. The four pathogenic CNVs > 10 Mbp included a chromosome 2q14.3q24.1 microduplication of 29.7 Mbp in size, a chromosome 5p15.33p14.1 deletion of 28.2 Mbp in size causing cri-du-chat syndrome, a chromosome 8q22.3q23.3 deletion of 11.2 Mbp in size causing 8q22.2q22.3 microdeletion syndrome 18,19,20 , and a tetrasomy of chromosome 18p of 15 Mbp in size. Three of these CNVs appeared in pregnancies tested for abnormal biochemical screening, and one in a pregnancy that was tested owing to advanced maternal age.…”

“…Overall, the risk for a clinically significant early-onset CNV (P/LP or SL > 10%, not including XLI) in the low-risk group was 1.12%, and 1.06% when including only findings < 10 Mbp. Information on each of the P/LP syndromes is given in Table S1 [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] , and detailed information on each of these pregnancies is given in Table S2. SLs > 10% are given in Table 3 [5][6][7][38][39][40][41] .…”

Efficacy of cochlear implants in children with borderline hearing who have already achieved significant language development with hearing aids

“…According to our etiologic diagnostic pipeline for pediatric CI candidates with SNHL, all available methods were used including internal auditory canal magnetic resonance imaging (IAC-MRI) and Molecular genetic testing (MGT). Except for subjects with already known etiologies, MGT was conducted with the following process: [ 1 ] U-Top screening kit [ 5 , 6 ] or Direct Sanger sequencing in subjects with a characteristic phenotype, such as enlarged vestibular aqueduct, [ 2 ] deafness panel sequencing (TES-129) [ 7 , 8 ] or exome sequencing [ 9 , 10 ], and [ 3 ] fluorescent in situ hybridization (FISH), if necessary [ 11 ]. Panel sequencing or exome sequencing results were analyzed as previously described [ 12 , 13 ].…”

Full etiologic spectrum of pediatric severe to profound hearing loss of consecutive 119 cases

“…Unless panel sequencing clearly revealed the causative variants, exome sequencing was performed. FISH was performed only for syndromic deafness with significant co-morbid abnormality, of which causative variants had not been elucidated after exome sequencing 56 . In all cases, genomic DNA was extracted from the peripheral blood.…”