Edinburgh Research Explorer

Microcephaly, intellectual impairment, bilateral vesicoureteral reflux, distichiasis, and glomuvenous malformations associated with a 16q24.3 contiguous gene deletion and a Glomulin mutation

Research output: Contribution to journalArticle

  • Matthew G Butler
  • Susan L Dagenais
  • José L Garcia-Perez
  • Pascal Brouillard
  • Miikka Vikkula
  • Peter Strouse
  • Jeffrey W Innis
  • Thomas W Glover

Related Edinburgh Organisations

Original languageEnglish
Pages (from-to)839-49
Number of pages11
JournalAmerican Journal of Medical Genetics Part A
Issue number4
Publication statusPublished - Apr 2012


Two hereditary syndromes, lymphedema-distichiasis (LD) syndrome and blepharo-chelio-dontic (BCD) syndrome include the aberrant growth of eyelashes from the meibomian glands, known as distichiasis. LD is an autosomal dominant syndrome primarily characterized by distichiasis and the onset of lymphedema usually during puberty. Mutations in the forkhead transcription factor FOXC2 are the only known cause of LD. BCD syndrome consists of autosomal dominant abnormalities of the eyelid, lip, and teeth, and the etiology remains unknown. In this report, we describe a proband that presented with distichiasis, microcephaly, bilateral grade IV vesicoureteral reflux requiring ureteral re-implantation, mild intellectual impairment and apparent glomuvenous malformations (GVM). Distichiasis was present in three generations of the proband's maternal side of the family. The GVMs were severe in the proband, and maternal family members exhibited lower extremity varicosities of variable degree. A GLMN (glomulin) gene mutation was identified in the proband that accounts for the observed GVMs; no other family member could be tested. TIE2 sequencing revealed no mutations. In the proband, an additional submicroscopic 265 kb contiguous gene deletion was identified in 16q24.3, located 609 kb distal to the FOXC2 locus, which was inherited from the proband's mother. The deletion includes the C16ORF95, FBXO31, MAP1LC3B, and ZCCHC14 loci and 115 kb of a gene desert distal to FOXC2 and FOXL1. Thus, it is likely that the microcephaly, distichiasis, vesicoureteral, and intellectual impairment in this family may be caused by the deletion of one or more of these genes and/or deletion of distant cis-regulatory elements of FOXC2 expression.

    Research areas

  • Adaptor Proteins, Signal Transducing, Child, Chromosome Mapping, Chromosomes, Human, Pair 16, DNA Copy Number Variations, Eyelashes, Female, Forkhead Transcription Factors, Gene Deletion, Genotype, Glomus Tumor, Humans, Intellectual Disability, Lymphedema, Magnetic Resonance Imaging, Microcephaly, Paraganglioma, Extra-Adrenal, Receptor, TIE-2, Vesico-Ureteral Reflux

ID: 25156618