Non lethal Raine syndrome and differential diagnosis

Eur J Med Genet. 2016 Nov;59(11):577-583. doi: 10.1016/j.ejmg.2016.09.018. Epub 2016 Sep 22.

Abstract

Raine syndrome is a rare autosomal recessive bone dysplasia characterized by characteristic facial features with exophthalmos and generalized osteosclerosis. Amelogenesis imperfecta, hearing loss, seizures, and intracerebral calcification are apparent in some affected individuals. Originally, Raine syndrome was originally reported as a lethal syndrome. However, recently a milder phenotype, compatible with life, has been described. Biallelic variants inFAM20C, encoding aGolgi casein kinase involved in biomineralisation, have been identified in affected individuals. We report here a consanguineous Moroccan family with two affected siblingsa girl aged 18 and a boy of 15years. Clinical features, including learning disability, seizures and amelogenesis imperfecta, initially suggested a diagnosis of Kohlschutter-Tonz syndrome. However,a novel homozygous FAM20Cvariantc.676T > A, p.(Trp226Arg) was identified in the affected siblings. Our report reinforces that Raine syndrome is compatible with life, and that mild hypophosphatemia and amelogenesis imperfecta are key features of the attenuated form.

Keywords: FAM20C gene; Kohlschutter-Tonz syndrome; Raine syndrome.

MeSH terms

  • Abnormalities, Multiple / diagnosis
  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / mortality
  • Abnormalities, Multiple / physiopathology
  • Adolescent
  • Amelogenesis Imperfecta / diagnosis
  • Amelogenesis Imperfecta / genetics*
  • Amelogenesis Imperfecta / mortality
  • Amelogenesis Imperfecta / physiopathology
  • Bone Diseases, Developmental / genetics
  • Bone Diseases, Developmental / mortality
  • Bone Diseases, Developmental / physiopathology
  • Casein Kinase I / genetics*
  • Cleft Palate / diagnosis
  • Cleft Palate / genetics*
  • Cleft Palate / mortality
  • Cleft Palate / physiopathology
  • Dementia / diagnosis
  • Dementia / genetics*
  • Dementia / mortality
  • Dementia / physiopathology
  • Diagnosis, Differential*
  • Epilepsy / diagnosis
  • Epilepsy / genetics*
  • Epilepsy / mortality
  • Epilepsy / physiopathology
  • Exophthalmos / diagnosis
  • Exophthalmos / genetics*
  • Exophthalmos / mortality
  • Exophthalmos / physiopathology
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Humans
  • Learning Disabilities / genetics
  • Learning Disabilities / physiopathology
  • Male
  • Microcephaly / diagnosis
  • Microcephaly / genetics*
  • Microcephaly / mortality
  • Microcephaly / physiopathology
  • Osteosclerosis / diagnosis
  • Osteosclerosis / genetics*
  • Osteosclerosis / mortality
  • Osteosclerosis / physiopathology
  • Phenotype
  • Seizures / genetics
  • Seizures / physiopathology

Substances

  • Extracellular Matrix Proteins
  • Casein Kinase I
  • FAM20C protein, human

Supplementary concepts

  • Kohlschutter Tonz syndrome
  • Raine syndrome