title: Brain malformations in a patient with deletion 2p16.1: A refinement of the phenotype to BCL11A.
abstract: Microdeletions of 2p15-16.1 have been reported in 15 patients with a recognizable syndrome of dysmorphic features, intellectual disability and microcephaly. Facial features include telecanthus, short palpebral fissures, epicanthal folds, a broad nasal root, smooth and long philtrum and large ears. Brain malformations can be observed in this syndrome and include hypoplasia of the corpus callosum and a simplified cortical gyral pattern. Case reports have narrowed the critical region of the neurodevelopmental phenotype to a region that spans the B-cell CLL/lymphoma 11A (BCL11A) gene. Here we present a 3-year-old normocephalic girl with moderate development delay and dysmorphic features including a prominent forehead, telecanthus, depressed nasal bridge, thin upper vermilion and a small chin. Magnetic resonance imaging shows enlargement of the lateral, third and fourth ventricles and hypoplastic corpus callosum, cerebellar vermis and pons. Array CGH revealed a 0.875 Mb de novo deletion at 2p16.1 that includes only BCL11A. The moderate delays, hypoplastic and dysmorphic corpus callosum and hippocampi and the facial features are in keeping with the previously described 2p15-16.1 microdeletion syndrome. However, hypoplasia of the pons and cerebellum are not commonly recognized features and are reminiscent of the brain malformations observed in individuals with a mutation in CASK. CASK is known to interact with BCL11A in the normal growth of axons. This case report highlights the role of BCL11A in 2p15-16.1 microdeletion syndrome and the unique phenotype suggests a common pathway for BCL11A and other genes in neurodevelopment.
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Canada.
authors.forename: Tugce B
authors.initials: TB
authors.lastname: Balci
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Canada.
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Sawyer
authors.affiliation: Department of Radiology, Children's Hospital of Eastern Ontario, Ottawa, Canada.
authors.forename: Jorge
authors.initials: J
authors.lastname: Davila
authors.affiliation: Department of Pediatrics, Division of Neurology, Children's Hospital of Eastern Ontario, Ottawa, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Humphreys
authors.affiliation: Department of Genetics, Children's Hospital of Eastern Ontario, Ottawa, Canada. Electronic address: ddyment@cheo.on.ca.
authors.forename: David A
authors.initials: DA
authors.lastname: Dyment
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics*; D001921:Brain / Q000002:abnormalities*; D002352:Carrier Proteins / Q000235:genetics*; D002675:Child, Preschool; D002872:Chromosome Deletion; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D051528:Guanylate Kinases / Q000235:genetics; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics*; D010641:Phenotype; D012097:Repressor Proteins
chemical_list: C486563:BCL11A protein, human; D002352:Carrier Proteins; D009687:Nuclear Proteins; D012097:Repressor Proteins; C106868:CASK kinases; D051528:Guanylate Kinases
keywords: 2p15-16.1 microdeletion syndrome; BCL11A; CASK; Pontocerebellar hypoplasia