Non lethal Raine syndrome and differential diagnosis.
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.
Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V Souissi, Rabat, Morocco; Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco. Electronic address: sihamgen@yahoo.fr.
Siham Chafai
SC
Elalaoui
Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK; Manchester Centre for Genomic Medicine, Institute of Human Development, University of Manchester, Manchester, M13 9WL, UK.
Nada
N
Al-Sheqaih
Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V Souissi, Rabat, Morocco.
Ilham
I
Ratbi
Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK; Manchester Centre for Genomic Medicine, Institute of Human Development, University of Manchester, Manchester, M13 9WL, UK.
Jill E
JE
Urquhart
Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK; Manchester Centre for Genomic Medicine, Institute of Human Development, University of Manchester, Manchester, M13 9WL, UK.
James
J
O'Sullivan
Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK.
Sanjeev
S
Bhaskar
Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK.
Simon S
SS
Williams
Service d'Odontologie Pédiatrique, Faculté de Médecine Dentaire, Université Mohammed V, Rabat, Morocco.
Mustapha
M
Elalloussi
Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V Souissi, Rabat, Morocco.
Jaber
J
Lyahyai
Service de Radiologie, Hopital Ibn Sina, Rabat, Morocco.
Leila
L
Sbihi
Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V Souissi, Rabat, Morocco; Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco.
Imane
I
Cherkaoui Jaouad
Cabinet de Radiologie de l'Agdal, Rabat, Morocco.
Abdelhafid
A
Sbihi
Manchester Centre for Genomic Medicine, St. Mary's Hospital, Manchester Academic Health Sciences Centre, Manchester, M13 9WL, UK; Manchester Centre for Genomic Medicine, Institute of Human Development, University of Manchester, Manchester, M13 9WL, UK.
William G
WG
Newman
Centre de Génomique Humaine, Faculté de Médecine et de Pharmacie, Université Mohammed V Souissi, Rabat, Morocco; Département de Génétique Médicale, Institut National d'Hygiène, Rabat, Morocco.
Abdelaziz
A
Sefiani
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D000293:Adolescent; D000567:Amelogenesis Imperfecta / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D001848:Bone Diseases, Developmental / Q000235:genetics / Q000401:mortality / Q000503:physiopathology; D047389:Casein Kinase I / Q000235:genetics*; D002972:Cleft Palate / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D003704:Dementia / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D003937:Diagnosis, Differential; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D005094:Exophthalmos / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics / Q000503:physiopathology; D008297:Male; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D010026:Osteosclerosis / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D010641:Phenotype; D012640:Seizures / Q000235:genetics / Q000503:physiopathology
D016326:Extracellular Matrix Proteins; D047389:Casein Kinase I; C524449:FAM20C protein, human
FAM20C gene; Kohlschutter-Tonz syndrome; Raine syndrome