Five patients with a chromosome 1q21.1 triplication show macrocephaly, increased weight and facial similarities.
Recurrent rearrangements of chromosome 1q21.1 that occur as a consequence of non-allelic homologous recombination (NAHR) show considerable variability in phenotypic expression and penetrance. Chromosome 1q21.1 deletions (OMIM 612474) have been associated with microcephaly, intellectual disability, autism, schizophrenia, cardiac abnormalities and cataracts. Phenotypic features in individuals with 1q21.1 duplications (OMIM 612475) include macrocephaly, learning difficulties, developmental delay, intellectual disability and mild dysmorphic features. Half of these patients show autistic behavior. For the first time, we describe five patients, including monozygotic twins, with a triplication of the 1q21.1 chromosomal segment. Facial features common to all patients include a high, broad forehead; a flat and broad nasal bridge; long, downslanted palpebral fissures and dysplastic, low-set ears. Likely associated features include macrocephaly and increased weight. We observed that the triplications arose through different mechanisms in the patients: it was de novo in one patient, inherited from a triplication carrier in two cases, while the father of the twins is a 1q21.1 duplication carrier. The de novo triplication contained copies of both maternal alleles, suggesting it was generated by a combination of inter- and intrachromosomal recombination.
['Van Dijck|Anke|A|', 'van der Werf|Ilse M|IM|', 'Reyniers|Edwin|E|', 'Scheers|Stefaan|S|', 'Azage|Meron|M|', 'Siefkas|Kiana|K|', 'Van der Aa|Nathalie|N|', 'Lacroix|Amy|A|', 'Rosenfeld|Jill|J|', 'Argiropoulos|Bob|B|', 'Davis|Kellie|K|', 'Innes|A Micheil|AM|', 'Mefford|Heather C|HC|', 'Mortier|Geert|G|', 'Meuwissen|Marije|M|', 'Kooy|R Frank|RF|']
D002648:Child D002675:Child, Preschool D002878:Chromosomes, Human, Pair 1 D019465:Craniofacial Abnormalities D005260:Female D006801:Humans D007223:Infant D008297:Male D058627:Megalencephaly D050177:Overweight D013577:Syndrome D014314:Trisomy D014430:Twins, Monozygotic
1q21.1 triplication Macrocephaly Recurrent rearrangements Genomic disorder Overweight