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.
Department of Medical Genetics, University of Antwerp, Belgium; Department of Medical Genetics, University Hospital Antwerp, Belgium. Electronic address: Anke.Vandijck@uantwerpen.be.
Anke
A
Van Dijck
Department of Medical Genetics, University of Antwerp, Belgium.
Ilse M
IM
van der Werf
Department of Medical Genetics, University of Antwerp, Belgium; Department of Medical Genetics, University Hospital Antwerp, Belgium.
Edwin
E
Reyniers
Department of Medical Genetics, University of Antwerp, Belgium; Department of Medical Genetics, University Hospital Antwerp, Belgium.
Stefaan
S
Scheers
Department of Medical Genetics, Children's Hospital of Pittsburgh, PA, USA.
Meron
M
Azage
Department of Medical Genetics, Seattle Children's Hospital, Seattle, WA, USA.
Kiana
K
Siefkas
Department of Medical Genetics, University of Antwerp, Belgium.
Nathalie
N
Van der Aa
Department of Pediatrics, University of Washington, Seattle, WA, USA.
Amy
A
Lacroix
Signature Genomic Laboratories, Spokane, WA, USA.
Jill
J
Rosenfeld
Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Bob
B
Argiropoulos
Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
Kellie
K
Davis
Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
A Micheil
AM
Innes
Department of Medical Genetics, Seattle Children's Hospital, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA.
Heather C
HC
Mefford
Department of Medical Genetics, University of Antwerp, Belgium; Department of Medical Genetics, University Hospital Antwerp, Belgium.
Geert
G
Mortier
Department of Medical Genetics, University Hospital Antwerp, Belgium.
Marije
M
Meuwissen
Department of Medical Genetics, University of Antwerp, Belgium.
R Frank
RF
Kooy
D002648:Child; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D058627:Megalencephaly / Q000175:diagnosis / Q000235:genetics*; D050177:Overweight / Q000175:diagnosis / Q000235:genetics*; D013577:Syndrome; D014314:Trisomy; D014430:Twins, Monozygotic / Q000235:genetics
1q21.1 triplication; Genomic disorder; Macrocephaly; Overweight; Recurrent rearrangements