MCID: RNS001
MIFTS: 45

Raine Syndrome

Categories: Genetic diseases, Rare diseases, Bone diseases, Fetal diseases, Ear diseases, Smell/Taste diseases

Aliases & Classifications for Raine Syndrome

MalaCards integrated aliases for Raine Syndrome:

Name: Raine Syndrome 57 76 53 59 75 37 29 13 6 40 73
Lethal Osteosclerotic Bone Dysplasia 53 59
Rns 57 75
Combination of Microcephaly, Exophthalmos, Hypoplastic Nose and Midface, Gum Hyperplasia, Cleft Palate, Apparently Low-Set Ears, and Osteosclerosis 53
Osteosclerotic Bone Dysplasia, Lethal 57

Characteristics:

Orphanet epidemiological data:

59
lethal osteosclerotic bone dysplasia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
some patients survive infancy


HPO:

32
raine syndrome:
Mortality/Aging neonatal death
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Raine Syndrome

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 1832Disease definitionLethal osteosclerotic bone dysplasia is defined by generalized osteosclerosis with periosteal bone formation, characteristic facial dysmorphism, brain abnormalities including intracerebral calcifications, and neonatal lethal course.EpidemiologyTen cases in eight families have been reported, the majority of a Middle East origin. Parental consanguinity was frequently present.Clinical descriptionThe cranial features are a wide anterior fontanelle, expressed proptosis with everted lower eyelids, severely depressed nasal bridge, small nose, low-set ears, and severe midface hypoplasia leading to choanal atresia. The mouth is usually triangular, gum hypertrophy is expressed, and there may be natal teeth and cleft palate/uvula. The radiological findings include generalized osteosclerosis of all bones and the base of the skull, with cortical hyperostosis and periosteal new bone formation. An obtuse mandibular angle is characteristic, as are irregularly formed ribs. Radiologically, widespread bilateral calcification in the periventricular white matter, basal ganglia, and thalamus is found and in some cases calcifications are also seen in the corpus callosum, falx, tentorium, and meninges. Extra-skeletal features can be hydronephrosis and ureteral stenosis.EtiologyMutations in the FAM20C gene have a causative role in lethal osteosclerotic bone dysplasia.Diagnostic methodsDiagnosis is based on clinical presentation and calcification demonstrable by ultrasound, plain X-rays and computing tomography (CT).Antenatal diagnosisPrenatal diagnosis by ultrasound or molecular testing is feasible.Genetic counselingThe condition is transmitted in an autosomal recessive manner.Visit the Orphanet disease page for more resources.

MalaCards based summary : Raine Syndrome, also known as lethal osteosclerotic bone dysplasia, is related to osteomalacia and hypophosphatemia. An important gene associated with Raine Syndrome is FAM20C (FAM20C, Golgi Associated Secretory Pathway Kinase). Affiliated tissues include bone, brain and testes, and related phenotypes are low-set ears and short neck

OMIM : 57 Raine syndrome is a neonatal osteosclerotic bone dysplasia of early and aggressive onset that usually results in death within the first few weeks 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 (summary by Simpson et al., 2009). (259775)

UniProtKB/Swiss-Prot : 75 Raine syndrome: Autosomal recessive osteosclerotic bone dysplasia with neonatal lethal outcome. Clinical features include generalized osteosclerosis, craniofacial dysplasia and microcephaly.

Wikipedia : 76 Raine syndrome (RNS), also called osteosclerotic bone dysplasia, is a rare autosomal recessive... more...

Related Diseases for Raine Syndrome

Graphical network of the top 20 diseases related to Raine Syndrome:



Diseases related to Raine Syndrome

Symptoms & Phenotypes for Raine Syndrome

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Ears:
low-set ears
dysplastic ears (in some patients)
posteriorly rotated ears (in some patients)
protruding ears (in some patients)
hearing loss, mixed (in some patients)

Head And Neck Mouth:
high palate
cleft palate
small mouth
gingival hyperplasia
wide mouth (in some patients)
more
Head And Neck Head:
microcephaly
brachycephaly
turribrachycephaly
plagiocephaly (in some patients)
wide fontanelles

Head And Neck Face:
micrognathia
midface hypoplasia
prognathism (in some patients)
choanal atresia or choanal stenosis
craniofacial dysplasia
more
Metabolic Features:
elevated alkaline phosphatase
low circulating phosphate

Skeletal Skull:
osteosclerosis

Skeletal Hands:
brachydactyly (in some patients)
bulbous fingertips (in some patients)
thick fingers (in some patients)

Head And Neck Teeth:
abnormal teeth (in some patients)
natal teeth (in some patients)
small teeth (in some patients)
enamel dysplasia (in some patients)

Genitourinary External Genitalia Male:
microscrotum (in some patients)

Genitourinary Ureters:
hydroureter, bilateral (in some patients)
stenotic ostia of ureters (in some patients)

Skeletal Spine:
absence of ossification of vertebral bodies c3 to c5 (rare)
vertebral segmentation defects (rare)

Skeletal Limbs:
short limbs (in some patients)
bowing of long bones (in some patients)

Neurologic Behavioral Psychiatric Manifestations:
self-stimulating behavior (in some patients)

Head And Neck Neck:
short neck

Head And Neck Nose:
depressed nasal bridge
hypoplastic nose

Growth Height:
short stature

Respiratory Lung:
pulmonary hypoplasia

Head And Neck Eyes:
downslanting palpebral fissures
exophthalmos
hypertelorism (in some patients)
arched eyebrows (in some patients)

Chest:
small thorax

Neurologic Central Nervous System:
cerebral calcifications
hydrocephalus (in some patients)
developmental delay (in some patients who survive infancy)

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum (in some patients)
multiple fracture-like rib lesions

Genitourinary Kidneys:
decreased tubular resorption of phosphate (in some patients)
hydronephrosis (in some patients)
double renal pelvis (in some patients)
renal cortex calcification (in some patients)

Skeletal:
osteosclerosis, generalized
arthrogryposis (rare)

Skeletal Pelvis:
absence of ossification of sacrum (rare)

Skeletal Feet:
large halluces (in some patients)


Clinical features from OMIM:

259775

Human phenotypes related to Raine Syndrome:

59 32 (show top 50) (show all 58)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 low-set ears 59 32 hallmark (90%) Very frequent (99-80%) HP:0000369
2 short neck 59 32 hallmark (90%) Very frequent (99-80%) HP:0000470
3 gingival overgrowth 59 32 frequent (33%) Frequent (79-30%) HP:0000212
4 short nose 59 32 frequent (33%) Frequent (79-30%) HP:0003196
5 microcephaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0000252
6 anteverted nares 59 32 hallmark (90%) Very frequent (99-80%) HP:0000463
7 micrognathia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000347
8 retrognathia 59 32 hallmark (90%) Very frequent (99-80%) HP:0000278
9 respiratory distress 59 32 frequent (33%) Frequent (79-30%) HP:0002098
10 intrauterine growth retardation 59 32 frequent (33%) Frequent (79-30%) HP:0001511
11 depressed nasal ridge 59 32 hallmark (90%) Very frequent (99-80%) HP:0000457
12 respiratory failure 59 32 frequent (33%) Frequent (79-30%) HP:0002878
13 proptosis 59 32 frequent (33%) Frequent (79-30%) HP:0000520
14 large fontanelles 59 32 hallmark (90%) Very frequent (99-80%) HP:0000239
15 median cleft lip and palate 59 32 hallmark (90%) Very frequent (99-80%) HP:0008501
16 delayed cranial suture closure 59 32 hallmark (90%) Very frequent (99-80%) HP:0000270
17 gingival fibromatosis 59 32 frequent (33%) Frequent (79-30%) HP:0000169
18 posteriorly rotated ears 59 32 occasional (7.5%) Very frequent (99-80%) HP:0000358
19 mandibular aplasia 59 32 frequent (33%) Frequent (79-30%) HP:0009939
20 malar flattening 32 HP:0000272
21 hypertelorism 32 HP:0000316
22 pectus excavatum 32 occasional (7.5%) HP:0000767
23 high palate 32 HP:0000218
24 hydrocephalus 32 occasional (7.5%) HP:0000238
25 cerebral calcification 32 HP:0002514
26 mandibular prognathia 32 occasional (7.5%) HP:0000303
27 global developmental delay 32 HP:0001263
28 depressed nasal bridge 32 HP:0005280
29 bowing of the long bones 32 occasional (7.5%) HP:0006487
30 short stature 32 HP:0004322
31 hypophosphatemia 32 HP:0002148
32 dyspnea 59 Frequent (79-30%)
33 cleft palate 32 HP:0000175
34 micromelia 32 occasional (7.5%) HP:0002983
35 microdontia 32 occasional (7.5%) HP:0000691
36 protruding ear 32 occasional (7.5%) HP:0000411
37 arthrogryposis multiplex congenita 32 occasional (7.5%) HP:0002804
38 wide mouth 32 occasional (7.5%) HP:0000154
39 downslanted palpebral fissures 32 HP:0000494
40 narrow mouth 32 HP:0000160
41 brachydactyly 32 occasional (7.5%) HP:0001156
42 protruding tongue 32 HP:0010808
43 choanal atresia 32 HP:0000453
44 increased bone mineral density 32 HP:0011001
45 midface retrusion 32 HP:0011800
46 highly arched eyebrow 32 occasional (7.5%) HP:0002553
47 hydronephrosis 32 occasional (7.5%) HP:0000126
48 plagiocephaly 32 occasional (7.5%) HP:0001357
49 hydroureter 32 occasional (7.5%) HP:0000072
50 brachyturricephaly 32 HP:0000244

MGI Mouse Phenotypes related to Raine Syndrome:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 limbs/digits/tail MP:0005371 9.13 DMP1 FAM20C FGF23
2 renal/urinary system MP:0005367 8.8 FGF23 DMP1 FAM20C

Drugs & Therapeutics for Raine Syndrome

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 FGF23 and Angiotensin-(1-7) in Hypophosphatemia (GAP) Not yet recruiting NCT03489993

Search NIH Clinical Center for Raine Syndrome

Genetic Tests for Raine Syndrome

Genetic tests related to Raine Syndrome:

# Genetic test Affiliating Genes
1 Raine Syndrome 29 FAM20C

Anatomical Context for Raine Syndrome

MalaCards organs/tissues related to Raine Syndrome:

41
Bone, Brain, Testes, Eye, Thalamus, Tongue, Cortex

Publications for Raine Syndrome

Articles related to Raine Syndrome:

(show all 28)
# Title Authors Year
1
A case of Raine syndrome presenting with facial dysmorphy and review of literature. ( 29751744 )
2018
2
Fetal ultrasonographic findings including cerebral hyperechogenicity in a patient with non-lethal form of Raine syndrome. ( 29341424 )
2018
3
Non lethal Raine syndrome and differential diagnosis. ( 27667191 )
2016
4
Raine Syndrome (OMIM #259775), Caused By FAM20C Mutation, Is Congenital Sclerosing Osteomalacia With Cerebral Calcification (OMIM 259660). ( 27862258 )
2016
5
Molecular Characterization of Three Canine Models of Human Rare Bone Diseases: Caffey, van den Ende-Gupta, and Raine Syndromes. ( 27187611 )
2016
6
Report of a case of Raine syndrome and literature review. ( 25974638 )
2015
7
Variability of systemic and oro-dental phenotype in two families with non-lethal Raine syndrome with FAM20C mutations. ( 25928877 )
2015
8
Raine syndrome. ( 24959018 )
2014
9
Raine syndrome: an overview. ( 25019372 )
2014
10
Hypophosphatemic osteomalacia and bone sclerosis caused by a novel homozygous mutation of the FAM20C gene in an elderly man with a mild variant of Raine syndrome. ( 24982027 )
2014
11
Functional analysis of mutant FAM20C in Raine syndrome with FGF23-related hypophosphatemia. ( 25026495 )
2014
12
Hereditary deletion of the entire FAM20C gene in a patient with Raine syndrome. ( 24039075 )
2013
13
The Raine syndrome protein FAM20C is a Golgi kinase that phosphorylates bio-mineralization proteins. ( 22900076 )
2012
14
Raine syndrome. ( 21948671 )
2011
15
Raine syndrome: expanding the radiological spectrum. ( 21076826 )
2011
16
Raine syndrome: a clinical, radiographic and genetic investigation of a case from the Indian subcontinent. ( 20453638 )
2010
17
Mutations in FAM20C are associated with lethal osteosclerotic bone dysplasia (Raine syndrome), highlighting a crucial molecule in bone development. ( 17924334 )
2007
18
Raine syndrome: a rare lethal osteosclerotic bone dysplasia. Prenatal diagnosis, autopsy, and neuropathological findings. ( 18000911 )
2007
19
Raine syndrome associated with cytomegalovirus infection. ( 15884638 )
2005
20
Raine syndrome: report of a family with three affected sibs and further delineation of the syndrome. ( 14564151 )
2003
21
Further delineation of Raine syndrome. ( 12868469 )
2003
22
Neuropathology of Raine syndrome. ( 11907809 )
2002
23
Raine syndrome: report of a case with hand and foot anomalies. ( 11446420 )
2001
24
Osteosclerosis, hypoplastic nose, and proptosis (Raine syndrome): further delineation. ( 10482879 )
1999
25
Intracranial calcification in Raine syndrome: radiological pathological correlation. ( 9799309 )
1998
26
Raine syndrome. ( 9714445 )
1998
27
Intracranial calcification in Raine syndrome. ( 8598998 )
1996
28
New distinct lethal osteosclerotic bone dysplasia (Raine syndrome). ( 1642277 )
1992

Variations for Raine Syndrome

UniProtKB/Swiss-Prot genetic disease variations for Raine Syndrome:

75
# Symbol AA change Variation ID SNP ID
1 FAM20C p.Gly379Glu VAR_037530 rs796051852
2 FAM20C p.Gly379Arg VAR_037531
3 FAM20C p.Leu388Arg VAR_037532 rs796051849
4 FAM20C p.Arg549Trp VAR_037533 rs796051850
5 FAM20C p.Ile258Asn VAR_073660
6 FAM20C p.Thr268Met VAR_073661 rs778899041
7 FAM20C p.Gly280Arg VAR_073662 rs779708323
8 FAM20C p.Pro328Ser VAR_073663 rs797044462
9 FAM20C p.Asp451Asn VAR_073664

ClinVar genetic disease variations for Raine Syndrome:

6
(show all 27)
# Gene Variation Type Significance SNP ID Assembly Location
1 FAM20C NM_020223.3(FAM20C): c.1093G> C (p.Gly365Arg) single nucleotide variant Pathogenic rs267606795 GRCh37 Chromosome 7, 295835: 295835
2 FAM20C NM_020223.3(FAM20C): c.1093G> C (p.Gly365Arg) single nucleotide variant Pathogenic rs267606795 GRCh38 Chromosome 7, 255869: 255869
3 FAM20C NM_020223.3(FAM20C): c.1163T> G (p.Leu388Arg) single nucleotide variant Pathogenic rs796051849 GRCh38 Chromosome 7, 255939: 255939
4 FAM20C NM_020223.3(FAM20C): c.1163T> G (p.Leu388Arg) single nucleotide variant Pathogenic rs796051849 GRCh37 Chromosome 7, 295905: 295905
5 FAM20C NM_020223.3(FAM20C): c.1645C> T (p.Arg549Trp) single nucleotide variant Pathogenic rs796051850 GRCh38 Chromosome 7, 259870: 259870
6 FAM20C NM_020223.3(FAM20C): c.1645C> T (p.Arg549Trp) single nucleotide variant Pathogenic rs796051850 GRCh37 Chromosome 7, 299836: 299836
7 FAM20C NM_020223.3(FAM20C): c.957-3C> G single nucleotide variant Pathogenic rs796051851 GRCh38 Chromosome 7, 248312: 248312
8 FAM20C NM_020223.3(FAM20C): c.957-3C> G single nucleotide variant Pathogenic rs796051851 GRCh37 Chromosome 7, 288278: 288278
9 FAM20C NM_020223.3(FAM20C): c.1136G> A (p.Gly379Glu) single nucleotide variant Pathogenic rs796051852 GRCh38 Chromosome 7, 255912: 255912
10 FAM20C NM_020223.3(FAM20C): c.1136G> A (p.Gly379Glu) single nucleotide variant Pathogenic rs796051852 GRCh37 Chromosome 7, 295878: 295878
11 FAM20C NM_020223.3(FAM20C): c.1364-2A> G single nucleotide variant Pathogenic rs796051853 GRCh38 Chromosome 7, 257003: 257003
12 FAM20C NM_020223.3(FAM20C): c.1364-2A> G single nucleotide variant Pathogenic rs796051853 GRCh37 Chromosome 7, 296969: 296969
13 FAM20C NM_020223.3(FAM20C): c.956+5G> C single nucleotide variant Pathogenic rs796051854 GRCh38 Chromosome 7, 246512: 246512
14 FAM20C NM_020223.3(FAM20C): c.956+5G> C single nucleotide variant Pathogenic rs796051854 GRCh37 Chromosome 7, 286478: 286478
15 FAM20C NM_020223.3(FAM20C): c.1446-1G> A single nucleotide variant Pathogenic rs796051855 GRCh38 Chromosome 7, 258645: 258645
16 FAM20C NM_020223.3(FAM20C): c.1446-1G> A single nucleotide variant Pathogenic rs796051855 GRCh37 Chromosome 7, 298611: 298611
17 FAM20C FAM20C, ASP437ASN single nucleotide variant Pathogenic
18 FAM20C NM_020223.3(FAM20C): c.737T> A (p.Ile246Asn) single nucleotide variant Pathogenic rs796051874 GRCh38 Chromosome 7, 195685: 195685
19 FAM20C NM_020223.3(FAM20C): c.737T> A (p.Ile246Asn) single nucleotide variant Pathogenic rs796051874 GRCh37 Chromosome 7, 195685: 195685
20 FAM20C NM_020223.3(FAM20C): c.796G> A (p.Gly266Arg) single nucleotide variant Pathogenic rs796051875 GRCh38 Chromosome 7, 208909: 208909
21 FAM20C NM_020223.3(FAM20C): c.796G> A (p.Gly266Arg) single nucleotide variant Pathogenic rs796051875 GRCh37 Chromosome 7, 208909: 208909
22 FAM20C NM_020223.3(FAM20C): c.982C> T (p.Pro328Ser) single nucleotide variant Pathogenic rs797044462 GRCh38 Chromosome 7, 248340: 248340
23 FAM20C NM_020223.3(FAM20C): c.982C> T (p.Pro328Ser) single nucleotide variant Pathogenic rs797044462 GRCh37 Chromosome 7, 288306: 288306
24 FAM20C NM_020223.3(FAM20C): c.1228T> A (p.Ser410Thr) single nucleotide variant Benign rs148276213 GRCh37 Chromosome 7, 295970: 295970
25 FAM20C NM_020223.3(FAM20C): c.1228T> A (p.Ser410Thr) single nucleotide variant Benign rs148276213 GRCh38 Chromosome 7, 256004: 256004
26 FAM20C NM_020223.3(FAM20C): c.1680C> A (p.Cys560Ter) single nucleotide variant Uncertain significance rs371584776 GRCh37 Chromosome 7, 299871: 299871
27 FAM20C NM_020223.3(FAM20C): c.1680C> A (p.Cys560Ter) single nucleotide variant Uncertain significance rs371584776 GRCh38 Chromosome 7, 259905: 259905

Copy number variations for Raine Syndrome from CNVD:

7
# CNVD ID Chromosom Start End Type Gene Symbol CNVD Disease
1 217128 7 1 7200000 Microdeletion Raine Syndrome

Expression for Raine Syndrome

Search GEO for disease gene expression data for Raine Syndrome.

Pathways for Raine Syndrome

GO Terms for Raine Syndrome

Cellular components related to Raine Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endoplasmic reticulum lumen GO:0005788 8.8 DMP1 FAM20C FGF23

Biological processes related to Raine Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 post-translational protein modification GO:0043687 9.33 DMP1 FAM20C FGF23
2 biomineral tissue development GO:0031214 8.96 DMP1 FAM20C
3 cellular protein metabolic process GO:0044267 8.8 DMP1 FAM20C FGF23

Sources for Raine Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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