Lacrimo-auriculo-dento-digital syndrome: A novel mutation in a Korean family and review of literature

Mol Genet Genomic Med. 2020 Oct;8(10):e1412. doi: 10.1002/mgg3.1412. Epub 2020 Jul 26.

Abstract

Background: Lacrimo-auriculo-dento-digital (LADD) syndrome is a rare autosomal dominant disorder caused by mutations in one of the three genes: fibroblast growth factor receptor 2 (FGFR2), FGFR3, or FGF10. Affected patients have hypoplasia/aplasia of lacrimal ducts/glands, hypoplasia/aplasia of salivary glands, dental anomalies, ear anomalies, hearing loss, and digital anomalies.

Case presentation: Proband was an 11-year-old male with xerostomia, xerophthalmia, and a referring diagnosis of Sjogren syndrome. He presented with microdontia, hypodontia, low-set/cupped ear auricles, and hearing loss in the left ear.

Methods: Whole exome sequencing (WES) was performed on proband. Variations and segregation within the family were verified using Sanger sequencing.

Results: Molecular studies revealed a novel heterozygous missense mutation in exon 11 of FGFR2: c.1547C>T (p.Ala516Val), compatible with LADD syndrome.

Conclusion: To the best of our knowledge, this is the first report of a family with LADD syndrome in Korea. The combination of xerostomia and xerophthalmia, seen in patients with LADD syndrome, may be misdiagnosed as Sjogren syndrome. WES may be a useful clinical tool in ascertaining the affected gene in patients with suspected genetic disorders. Here, a literature review and summary of 23 case reports/series of LADD syndrome are presented, which may help to identify patients with this condition.

Keywords: Sjogren syndrome; lacrimo-auriculo-dento-digital (LADD) syndrome; salivary gland agenesis; xerostomia.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics*
  • Adult
  • Child
  • Diagnosis, Differential
  • Hearing Loss / diagnosis
  • Hearing Loss / genetics*
  • Humans
  • Lacrimal Apparatus Diseases / diagnosis
  • Lacrimal Apparatus Diseases / genetics*
  • Male
  • Mutation, Missense
  • Pedigree
  • Receptor, Fibroblast Growth Factor, Type 2 / genetics*
  • Salivary Glands / pathology
  • Sjogren's Syndrome / diagnosis
  • Syndactyly / diagnosis
  • Syndactyly / genetics*
  • Tooth Abnormalities / diagnosis
  • Tooth Abnormalities / genetics*

Substances

  • FGFR2 protein, human
  • Receptor, Fibroblast Growth Factor, Type 2

Supplementary concepts

  • Lacrimoauriculodentodigital syndrome