IDC10-Code = Q78.2
Genomic coordinate (human 7:192,571 FAM20C).
Cytoband (human 7p22.3 FAM20C).
Intraband %= 6.88% FAM20C
OMIM’ genes @ 7p22.3 = 45 genes.
ClinVar = 500 FAM20C variants reported, with 53 classified pathogenic.
Parabolic Umbilic Chromosome-7 is 862 genes.
Chromosome-7 Cytobands: WGB2G5C_CWGBG10
Here I 🎁 present: “Raine Syndrome”, Victor McKusick, Mendelian Inheritance in Man’, 1966. (FAM20C)
INTRODUCTION.
Raine syndrome, also called osteosclerotic bone dysplasia, is a
congenital disorder characterized by craniofacial anomalies including microcephaly, noticeably low set ears, osteosclerosis, a cleft palate, gum hyperplasia, a hypoplastic nose, and eye proptosis. It is considered to be a lethal disease and usually leads to death within hours of birth.
Raine syndrome is a neonatal osteosclerotic bone dysplasia of early and aggressive onset that usually results in death within the first week of life, although there have been some reports of survival into childhood. Radiographic studies show a generalized increase in the density of all bones and a marked increase in the ossification of the skull. The increased ossification of the basal structures of the skull and facial bones underlies the characteristic facial features, which include narrow prominent forehead, proptosis, depressed nasal bridge, and midface hypoplasia. Periosteal bone formation is also characteristic of this disorder and differentiates it from osteopetrosis and other known lethal and nonlethal osteosclerotic bone dysplasias. The periosteal bone formation typically extends along the diaphysis of long bones adjacent to areas of cellular soft tissue.
Raine Syndrome is characterized by the upstream failure of the kinase FAM20C, which prevents the normal phosphorylation of DMP1 (Dentinsialophosphoprotein-binding matrix protein-1).
Here is the step-by-step breakdown of how this disruption causes Raine Syndrome:
The Normal State (Left Side)
FAM20C Kinase: Located on chromosome 7p22.3, it acts as an upstream phosphorylation operator.
Normal Phosphorylation: FAM20C phosphorylates DMP1 into its active form DMP1^{P}.
Osteocyte Function: Active DMP1 leads to healthy osteocyte maturation, normal matrix organization, and stable phosphate regulation via FGF23 signaling (12p13.32).
The Diseased State / Raine Syndrome (Right Side)
FAM20C Failure: Mutations or failure in FAM20C stop the phosphorylation process.
DMP1 Dysfunction: DMP1 remains unphosphorylated (represented by the red ball balancing on the critical precipice).
Bone Defects: This dysfunction leads directly to Osteocyte Maturation Failure and a Mineralization Defect.
Systemic Stress: The outcome is Mineralization Stress, characterized by a defective, poorly organized bone matrix and severe disruptions to the broader endocrine phosphate-vitamin D-axis (involving CYP27B1 and VDR).
