A 54 Mb 11qter duplication and 0.9 Mb 1q44 deletion in a child with laryngomalacia and agenesis of corpus callosum

Abstract

BackgroundPartial Trisomy 11q syndrome (or Duplication 11q) has defined clinical features and is documented as a rare syndrome by National Organization of Rare Disorders (NORD). Deletion 1q44 (or Monosomy 1q44) is a well-defined syndrome, but there is controversy about the genes lying in 1q44 region, responsible for agenesis of the corpus callosum. We report a female child with the rare Partial Trisomy 11q syndrome and Deletion 1q44 syndrome. The genomic imbalance in the proband was used for molecular characterization of the critical genes in 1q44 region for agenesis of corpus callosum. Some genes in 11q14q25 may be responsible for laryngomalacia.ResultsWe report a female child with dysmorphic features, microcephaly, growth retardation, seizures, acyanotic heart disease, and hand and foot deformities. She had agenesis of corpus callosum, laryngomalacia, anterior ectopic anus, esophageal reflux and respiratory distress. Chromosome analysis revealed a derivative chromosome 1. Her karyotype was 46,XX,der(1)t(1;11)(q44;q14)pat. The mother had a normal karyotype and the karyotype of the father was 46,XY,t(1;11)(q44;q14). SNP array analysis showed that the proband had a 54 Mb duplication of 11q14q25 and a 0.9 Mb deletion of the submicroscopic subtelomeric 1q44 region. Fluorescence Insitu Hybridisation confirmed the duplication of 11qter and deletion of 1qter.ConclusionLaryngomalacia or obstruction of the upper airway is the outcome of increased dosage of some genes due to Partial Trisomy 11q Syndrome. In association with other phenotypic features, agenesis of corpus callosum appears to be a landmark phenotype for Deletion 1q44 syndrome, the critical genes lying proximal to SMYD3 in 1q44 region.

Chromosomal‐array analysis reveals partial 11q duplication and partial 12p deletion in a mildly affected case

“…All patients suffered from motor/mental disability except one (Table ). Partial trisomy 11q accompanied by monosomy 12q [Klaassens et al, ] and monosomy 1q44 [Lall et al, ] had usual manifestations such as short neck, upslanting and short palpebral fissures, thin lips, high palate, micrognathia, respiratory distress, ASD, PDA, and hypoplastic nails which were all present in the case reported herein. Additionally the case also has previously unreported features like uplifted ear lobules, inverted nipples, and short halluces.…”

“…To date, both pure partial trisomy 11q [Greig et al, ; Forsythe et al, ; Pfeiffer and Schutz, ; De Die Smulders and Engelen, ; Delobel et al, ; Zhao et al, ; Yelavarthi and Zunich, ; Partida‐Perez et al, ; Zarate et al, ; Zimberg‐Bossira et al, ] as well as partial trisomy 11q accompanied by other chromosomal anomalies have been reported [Klaassens et al, ; Lall et al, ]. The breakpoint regions in some cases, such as the one reported by Zhao et al [] as 11q13–25, Zarate et al [] as 11q14.1–q21, and Lall et al [] as 11q14–q25 were almost identical to the case reported herein. The clinical abnormalities of trisomy 11q were detailed in 1977 by Francke et al [] who recognized it as “duplication 11(q21/23(qter) syndrome”.…”

“…Constitutional partial trisomy 11q is most frequently due to abnormal segregation of a balanced parental t(11;22), resulting in a derivative chromosome 22 with partial trisomy 11q [Yelavarthi and Zunich, ; Klaassens et al, ]. Translocations involving 11q with autosomes other than 22 have also been described [Francke et al, ; Zhao et al, ; Lall et al, ]. In all those cases, unbalanced progeny was also a carrier for loss or gain of material for the autosome involved in translocation [Pfeiffer and Schutz, ].…”

Pre- and Postnatal Analysis of Chromosome 1q44 Deletion in Agenesis of Corpus Callosum

“…Caliebe et al [2010] described 2 patients with speech delay, seizures and variable corpus callosum thickness and overlapping deletions in the chromosomal region 1q44, but there was no deletion of AKT3 . ACC appears to be a landmark phenotype for deletion 1q44 syndrome, and the critical genes are proximal to SMYD3 in the 1q44 region, excluding the AKT3 gene [Lall et al, 2011].…”

Familial 3-Way Balanced Translocation Causes 1q43→qter Loss and 10q25.2→qter Gain in a Severely Affected Male Toddler

“…Fig. 2) [UCSC Genome Browser; Lall et al, 2011]. This gene -not yet considered morbid -is highly expressed in the developing fetal heart.…”