Craniosynostosis with Ectopia Lentis and a Homozygous 20-base Deletion in ADAMTSL4

• Published in: Ophthalmic genetics 2013-03, Vol.34 (1-2), p.78-82
• Main Authors: Chandra, Aman, Aragon-Martin, Jose Antonio, Sharif, Saba, Parulekar, Manoj, Child, Anne, Arno, Gavin
• Format: Article
• Language: English
• Subjects: ADAMTS Proteins; Base Sequence; Craniosynostoses - genetics; Ectopia Lentis - genetics; Exons - genetics; Female; Homozygote; Humans; Infant; Molecular Sequence Data; Mutation; Pedigree; Sequence Deletion; Thrombospondins - genetics
• ISSN: 1381-6810; 1744-5094
• DOI: 10.3109/13816810.2012.710707

Craniosynostosis with ectopia lentis has been described five times since 1950 with unknown inheritance and variable phenotype. The patient was diagnosed with right coronal synostosis at age 10 weeks requiring surgery, and bilateral ectopia lentis with high myopia at 10 months. No other family member was affected. There is no known consanguinity within the family. Genetic screening ruled out FBN1, TGFBR2, and the known craniosynostosis hotspots (FGFR2 exon 8 and exon 10 and FGFR3 exon 6) as the cause. A homozygous deletion in exon 6 of ADAMTSL4 (c.767_786del 20) that has been shown to cause isolated ectopia lentis was found. The mutation results in a premature termination codon (p.Gln256ProfsX38). The proband's mother, father and one sibling are heterozygous carriers of the mutation. This is the first detailed report of a possible genetic determinant of craniosynostosis with ectopia lentis. Although this mutation causes isolated ectopia lentis, this may be evidence of pleiotropic effects of ADAMTSL4 and may represent an overlapping syndrome with a causative mutation in ADAMTSL4. These findings need to be confirmed in further cases with craniosynostosis and ectopia lentis.