MCID: OST022
MIFTS: 49

Osteopathia Striata with Cranial Sclerosis

Categories: Genetic diseases, Rare diseases, Bone diseases, Fetal diseases

Aliases & Classifications for Osteopathia Striata with Cranial Sclerosis

MalaCards integrated aliases for Osteopathia Striata with Cranial Sclerosis:

Name: Osteopathia Striata with Cranial Sclerosis 53 12 71 36 28 13 14
Hyperostosis Generalisata with Striations 53 12 49 55 71
Robinow-Unger Syndrome 12 49 55 71
Osteopathia Striata Cranial Sclerosis 49 41 69
Oscs 53 49 71
Osteopathia Striata-Cranial Sclerosis Syndrome 49 55
Osteopathia Striata - Cranial Sclerosis 49
Voorhoeve Disease 49

Characteristics:

Orphanet epidemiological data:

55
osteopathia striata-cranial sclerosis syndrome
Inheritance: X-linked dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
Miscellaneous:
one-third of cases are sporadic
increased morbidity/mortality in affected males
onset of linear striations between 5 months and 6 years (only in affected females)

Inheritance:
x-linked dominant


HPO:

31
osteopathia striata with cranial sclerosis:
Inheritance x-linked dominant inheritance


Classifications:



Summaries for Osteopathia Striata with Cranial Sclerosis

OMIM : 53 Osteopathia striata with cranial sclerosis is an X-linked dominant sclerosing bone dysplasia that presents in females with macrocephaly, cleft palate, mild learning disabilities, sclerosis of the long bones and skull, and longitudinal striations visible on radiographs of the long bones, pelvis, and scapulae (Jenkins et al., 2009). In males, the disorder is usually associated with fetal or neonatal lethality. Occasional surviving males have, in addition to hyperostosis, cardiac, intestinal, and genitourinary malformations. Osteosclerosis in the cranial and facial bones leads to disfigurement and to disability due to pressure on cranial nerves, e.g., deafness. Osteopathia striata is a frequent feature of focal dermal hypoplasia (FDH; 305600). Although early reports of familial cases of this disorder appeared to suggest autosomal dominant inheritance (see, e.g., Horan and Beighton, 1978 and Konig et al., 1996), reappraisal of the literature (Behninger and Rott, 2000; Rott et al., 2003) and the finding of a molecular basis for the disorder by Jenkins et al. (2009) confirms that the inheritance pattern is X-linked dominant. Affected males who survive have a more severe phenotype than affected females, and sporadic male cases may result from somatic mosaicism (Behninger and Rott, 2000). (300373)

MalaCards based summary : Osteopathia Striata with Cranial Sclerosis, also known as hyperostosis generalisata with striations, is related to hyperostosis and cleft palate, isolated, and has symptoms including macrocephaly, low-set ears and frontal bossing. An important gene associated with Osteopathia Striata with Cranial Sclerosis is AMER1 (APC Membrane Recruitment Protein 1), and among its related pathways/superpathways are Colorectal Cancer Metastasis and MicroRNAs in cardiomyocyte hypertrophy. Affiliated tissues include bone, heart and eye, and related phenotypes are cardiovascular system and growth/size/body region

UniProtKB/Swiss-Prot : 71 Osteopathia striata with cranial sclerosis: An X-linked dominant sclerosing bone dysplasia that presents in females with macrocephaly, cleft palate, facial palsy, conductive hearing loss, mild learning disabilities, sclerosis of the long bones and skull. Longitudinal striations are visible on radiographs of the long bones, pelvis, and scapulae (osteopathia striata). In males this entity is usually associated with fetal or neonatal lethality. Occasional surviving males have, in addition to hyperostosis, cardiac, intestinal, and genitourinary malformations.

NIH Rare Diseases : 49 Osteopathia striata cranial sclerosis is a type of skeletal dysplasia, which refers to a group of genetic conditions that affect the bones and hinder growth and development. The severity of the condition and the associated symptoms vary significantly from person to person, even within a single family. Features of the condition are generally present at birth and may include skeletal abnormalities (particularly at the ends of long bones), sclerosis (hardening) of the craniofacial bones, macrocephaly (unusually large head size), and characteristic facial features. Some affected people may also have developmental delay, hearing loss, heart defects and/or ophthalmoplegia (paralysis of the muscles surrounding the eyes). Osteopathia striata cranial sclerosis is caused by changes (mutations) in the WTX gene and is inherited in an X-linked dominant manner. Treatment is based on the signs and symptoms present in each person. Last updated: 12/9/2015

Disease Ontology : 12 An osteosclerosis characterized by longitudinal striations of the metaphyses of the long bones, sclerosis of the craniofacial bones, macrocephaly, cleft palate and hearing loss in females and fetal or neonatal lethality in males that has material basis in mutation in the AMER1 gene on chromosome Xq11.

Related Diseases for Osteopathia Striata with Cranial Sclerosis

Diseases related to Osteopathia Striata with Cranial Sclerosis via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 14)
# Related Disease Score Top Affiliating Genes
1 hyperostosis 29.7 LRP5 TNFRSF11B
2 cleft palate, isolated 10.2
3 wilms tumor 5 10.2
4 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.2
5 wilms tumor 6 10.2
6 spinal stenosis 10.2
7 osteomyelitis 10.2
8 cervicitis 10.2
9 hepatoblastoma 10.2
10 celiac disease 1 9.9
11 bone resorption disease 9.8 LRP5 TNFRSF11B
12 bone remodeling disease 9.7 LRP5 TNFRSF11B
13 endosteal hyperostosis, autosomal dominant 9.5 AMER1 LRP5 TNFRSF11B
14 osteoporosis 8.9 LRP5 TGFBR1 TNFRSF11B

Graphical network of the top 20 diseases related to Osteopathia Striata with Cranial Sclerosis:



Diseases related to Osteopathia Striata with Cranial Sclerosis

Symptoms & Phenotypes for Osteopathia Striata with Cranial Sclerosis

Symptoms via clinical synopsis from OMIM:

53
Head And Neck Head:
macrocephaly
widened sutures
delayed closure of anterior fontanelle
large fontanelle

Head And Neck Ears:
low-set ears
posteriorly rotated ears
small ears
hearing loss, conductive
overfolded ears

Head And Neck Face:
frontal bossing
facial palsy
micrognathia
bitemporal narrowing

Skeletal Skull:
thickened calvaria
occipital bossing
sclerotic cranial base
sclerotic mastoids (31%)
cranial sclerosis
more
Head And Neck Mouth:
cleft palate
bifid uvula
cleft lip
pierre robin sequence (in males)
thick lips (in males)
more
Head And Neck Neck:
webbed neck

Respiratory:
apnea

Voice:
nasal speech

Respiratory Nasopharynx:
tracheomalacia
paranasal sinus hypoplasia

Respiratory Larynx:
laryngeal web

Head And Neck Teeth:
malocclusion
crowded teeth
natal teeth

Skeletal Limbs:
short fibulae
absent fibulae

Skeletal Feet:
toe contractures
club feet (in males)

Growth Other:
failure to thrive (in males)

Genitourinary Kidneys:
multicystic kidney (rare, in males)
nephrogenic rests (rare, in males)

Head And Neck Eyes:
hypertelorism
epicanthal folds

Chest RibsSternum Clavicles And Scapulae:
pectus excavatum
broad, flat ribs
long, straight clavicles
broad medial and lateral clavicles

Neurologic Central Nervous System:
hydrocephalus
headaches
speech delay (10%)
transitional facial palsy (15%)
hypotonia (in males)
more
Abdomen Gastroin testinal:
gastroesophageal reflux
intestinal malrotation (rare, in males)
anal stenosis (rare, in males)
anal atresia (rare, in males)

Cardiovascular Vascular:
patent ductus arteriosus

Cardiovascular Heart:
atrial septal defect
ventricular septal defect

Prenatal Manifestations Amniotic Fluid:
polyhydramnios
oligohydramnios

Skeletal Spine:
spina bifida occulta
thoracolumbar gibbus
scoliosis (23%)

Skeletal Hands:
camptodactyly
fifth finger clinodactyly
long, slender fingers
finger contractures
duplicate phalanges
more
Head And Neck Nose:
broad nasal bridge

Chest Breasts:
widely spaced nipples

Skeletal:
joint contractures
osteopathia striata (linear striations of long bone diametaphyses, only in females)
increased trabecular thickness seen on iliac bone biopsy

Growth Height:
short stature (in males)

Abdomen External Features:
omphalocele (rare, in males)

Muscle Soft Tissue:
nemaline myopathy (in 1 reported male)


Clinical features from OMIM:

300373

Human phenotypes related to Osteopathia Striata with Cranial Sclerosis:

55 31 (show top 50) (show all 99)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 55 31 frequent (33%) Frequent (79-30%) HP:0000256
2 low-set ears 55 31 occasional (7.5%) Occasional (29-5%) HP:0000369
3 frontal bossing 55 31 frequent (33%) Frequent (79-30%) HP:0002007
4 intellectual disability 55 31 occasional (7.5%) Occasional (29-5%) HP:0001249
5 dysphasia 55 31 occasional (7.5%) Occasional (29-5%) HP:0002357
6 cerebral calcification 55 31 occasional (7.5%) Occasional (29-5%) HP:0002514
7 scoliosis 55 31 very rare (1%) Frequent (79-30%) HP:0002650
8 hyperlordosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0003307
9 facial palsy 55 31 occasional (7.5%) Occasional (29-5%) HP:0010628
10 cataract 55 31 occasional (7.5%) Occasional (29-5%) HP:0000518
11 global developmental delay 55 31 occasional (7.5%) Occasional (29-5%) HP:0001263
12 wide nasal bridge 55 31 frequent (33%) Frequent (79-30%) HP:0000431
13 thickened calvaria 55 31 hallmark (90%) Very frequent (99-80%) HP:0002684
14 brachycephaly 55 31 occasional (7.5%) Occasional (29-5%) HP:0000248
15 prominent forehead 55 31 frequent (33%) Frequent (79-30%) HP:0011220
16 cleft palate 55 31 Frequent (79-30%) HP:0000175
17 micrognathia 55 31 occasional (7.5%) Occasional (29-5%) HP:0000347
18 abnormality of the metaphysis 55 31 hallmark (90%) Very frequent (99-80%) HP:0000944
19 retrognathia 55 31 occasional (7.5%) Occasional (29-5%) HP:0000278
20 delayed eruption of teeth 55 31 frequent (33%) Frequent (79-30%) HP:0000684
21 epicanthus 55 31 occasional (7.5%) Occasional (29-5%) HP:0000286
22 large iliac wings 55 31 hallmark (90%) Very frequent (99-80%) HP:0008818
23 flat face 55 31 occasional (7.5%) Occasional (29-5%) HP:0012368
24 specific learning disability 55 31 occasional (7.5%) Occasional (29-5%) HP:0001328
25 high, narrow palate 55 31 frequent (33%) Frequent (79-30%) HP:0002705
26 coarctation of aorta 55 31 occasional (7.5%) Occasional (29-5%) HP:0001680
27 aphasia 55 31 occasional (7.5%) Occasional (29-5%) HP:0002381
28 conductive hearing impairment 55 31 frequent (33%) Frequent (79-30%) HP:0000405
29 flat occiput 55 31 frequent (33%) Frequent (79-30%) HP:0005469
30 severe short stature 55 31 occasional (7.5%) Occasional (29-5%) HP:0003510
31 spina bifida occulta 55 31 occasional (7.5%) Occasional (29-5%) HP:0003298
32 large fontanelles 55 31 frequent (33%) Frequent (79-30%) HP:0000239
33 bifid uvula 55 31 frequent (33%) Frequent (79-30%) HP:0000193
34 aortic valve stenosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0001650
35 rough bone trabeculation 55 31 hallmark (90%) Very frequent (99-80%) HP:0100670
36 submucous cleft hard palate 55 31 frequent (33%) Frequent (79-30%) HP:0000176
37 delayed cranial suture closure 55 31 frequent (33%) Frequent (79-30%) HP:0000270
38 osteopetrosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0011002
39 asymmetry of the thorax 55 31 occasional (7.5%) Occasional (29-5%) HP:0001555
40 posteriorly rotated ears 55 31 occasional (7.5%) Occasional (29-5%) HP:0000358
41 echolalia 55 31 occasional (7.5%) Occasional (29-5%) HP:0010529
42 mutism 55 31 occasional (7.5%) Occasional (29-5%) HP:0002300
43 facial hyperostosis 55 31 hallmark (90%) Very frequent (99-80%) HP:0005465
44 high iliac wings 55 31 hallmark (90%) Very frequent (99-80%) HP:0008808
45 headache 31 occasional (7.5%) HP:0002315
46 seizures 31 HP:0001250
47 hypertelorism 31 HP:0000316
48 pectus excavatum 31 HP:0000767
49 high palate 31 very rare (1%) HP:0000218
50 hydrocephalus 31 HP:0000238

UMLS symptoms related to Osteopathia Striata with Cranial Sclerosis:


headache, apnea

MGI Mouse Phenotypes related to Osteopathia Striata with Cranial Sclerosis:

43
# Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 9.67 AMER1 LRP5 TGFBR1 TNFRSF11B
2 growth/size/body region MP:0005378 9.65 AMER1 LRP5 TGFBR1 TNFRSF11B YARS
3 embryo MP:0005380 9.62 AMER1 LRP5 TGFBR1 YARS
4 mortality/aging MP:0010768 9.35 TNFRSF11B YARS AMER1 LRP5 TGFBR1
5 limbs/digits/tail MP:0005371 9.33 AMER1 LRP5 TNFRSF11B
6 skeleton MP:0005390 8.92 AMER1 LRP5 TGFBR1 TNFRSF11B

Drugs & Therapeutics for Osteopathia Striata with Cranial Sclerosis

Search Clinical Trials , NIH Clinical Center for Osteopathia Striata with Cranial Sclerosis

Cochrane evidence based reviews: osteopathia striata cranial sclerosis

Genetic Tests for Osteopathia Striata with Cranial Sclerosis

Genetic tests related to Osteopathia Striata with Cranial Sclerosis:

# Genetic test Affiliating Genes
1 Osteopathia Striata with Cranial Sclerosis 28 AMER1

Anatomical Context for Osteopathia Striata with Cranial Sclerosis

MalaCards organs/tissues related to Osteopathia Striata with Cranial Sclerosis:

38
Bone, Heart, Eye, Kidney

Publications for Osteopathia Striata with Cranial Sclerosis

Articles related to Osteopathia Striata with Cranial Sclerosis:

(show all 30)
# Title Authors Year
1
Genetic and molecular insights into genotype-phenotype relationships in osteopathia striata with cranial sclerosis (OSCS) through the analysis of novel mouse Wtx mutant alleles. ( 29329488 )
2018
2
First female prenatal case of osteopathia striata with cranial sclerosis in a fetus carrying a de-novo 1.9a88Mbp interstitial deletion at Xq11.1q11.2. ( 28799946 )
2017
3
A Case Study of a Preadolescent With Osteopathia Striata With Cranial Sclerosis. ( 28390856 )
2017
4
Novel AMER1 frameshift mutation in a girl with osteopathia striata with cranial sclerosis. ( 28990699 )
2017
5
Male child with somatic mosaic Osteopathia Striata with Cranial Sclerosis caused by a novel pathogenic AMER1 frameshift mutation. ( 28497491 )
2017
6
Osteopathia striata with cranial sclerosis and Wilms tumor: Coincidence or consequence? ( 29120061 )
2017
7
First case of osteopathia striata with cranial sclerosis in an adult male with Klinefelter syndrome. ( 27369646 )
2016
8
Germline mosaicism in osteopathia striata with cranial sclerosis - recurrence in siblings. ( 26886897 )
2016
9
Osteopathia striata with cranial sclerosis (OSCS): review of the literature and case report demonstrating challenges of spinal fusion after trauma. ( 27068044 )
2016
10
Osteopathia striata with cranial sclerosis: when a fetal malformation syndrome reveals maternal pathology. ( 25296999 )
2015
11
Prenatal diagnosis of osteopathia striata with cranial sclerosis. ( 25284440 )
2015
12
A novel WTX mutation in a female patient with osteopathia striata with cranial sclerosis and hepatoblastoma. ( 24459086 )
2014
13
Osteomyelitis in an Osteopathia Striata with Cranial Sclerosis Patient. ( 27489848 )
2014
14
Severe osteopathia striata with cranial sclerosis in a female case with whole WTX gene deletion. ( 23401208 )
2013
15
Dental findings in a child with osteopathia striata with cranial sclerosis (OS-CS): a case report. ( 24046992 )
2013
16
Osteopathia striata with cranial sclerosis and developmental delay in a male with a mosaic deletion in chromosome region Xq11.2. ( 22987541 )
2012
17
Two novel WTX mutations underscore the unpredictability of male survival in osteopathia striata with cranial sclerosis. ( 20950377 )
2011
18
Mosaicism in osteopathia striata with cranial sclerosis. ( 20150574 )
2010
19
Osteopathia striata with cranial sclerosis owing to WTX gene defect. ( 20209645 )
2010
20
Surgically assisted rapid maxillary expansion in two cases of osteopathia striata with cranial sclerosis. ( 18452358 )
2008
21
Osteopathia striata with cranial sclerosis and lumbar spinal stenosis. ( 17558457 )
2007
22
Osteopathia striata with cranial sclerosis and hearing loss. ( 16010569 )
2006
23
Osteopathia striata with cranial sclerosis: clinical, radiological, and bone histological findings in an adolescent girl. ( 15266607 )
2004
24
Severe cervical kyphosis in osteopathia striata with cranial sclerosis: case report. ( 11512010 )
2001
25
Osteopathia striata with cranial sclerosis: literature reappraisal argues for X-linked inheritance. ( 10893667 )
2000
26
Clinical vignette: osteopathia striata with cranial sclerosis. ( 9893078 )
1999
27
Severe malformations in males from families with osteopathia striata with cranial sclerosis. ( 9842992 )
1998
28
Further clinical delineation and increased morbidity in males with osteopathia striata with cranial sclerosis: an X-linked disorder? ( 9128936 )
1997
29
Osteopathia striata with cranial sclerosis: highly variable phenotypic expression within a family. ( 9383023 )
1997
30
How to counsel in osteopathia striata with cranial sclerosis. ( 9327263 )
1997

Variations for Osteopathia Striata with Cranial Sclerosis

ClinVar genetic disease variations for Osteopathia Striata with Cranial Sclerosis:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 AMER1 AMER1, 1-BP DEL, 671C deletion Pathogenic
2 AMER1 AMER1, 1-BP INS, 780A insertion Pathogenic
3 AMER1 AMER1, DEL deletion Pathogenic
4 AMER1 NM_152424.3(AMER1): c.1057C> T (p.Arg353Ter) single nucleotide variant Pathogenic rs137852216 GRCh37 Chromosome X, 63412110: 63412110
5 AMER1 NM_152424.3(AMER1): c.1072C> T (p.Arg358Ter) single nucleotide variant Pathogenic rs137852217 GRCh37 Chromosome X, 63412095: 63412095
6 AMER1 NM_152424.3(AMER1): c.429T> A (p.Cys143Ter) single nucleotide variant Pathogenic rs387906722 GRCh37 Chromosome X, 63412738: 63412738
7 AMER1 NM_152424.3(AMER1): c.1267delC (p.Leu423Trpfs) deletion Pathogenic rs398122877 GRCh37 Chromosome X, 63411900: 63411900
8 AMER1 NM_152424.3(AMER1): c.811C> T (p.Gln271Ter) single nucleotide variant Pathogenic rs387907269 GRCh37 Chromosome X, 63412356: 63412356
9 AMER1 NM_152424.3(AMER1): c.655delG (p.Glu219Argfs) deletion Likely pathogenic GRCh38 Chromosome X, 64192632: 64192632

Expression for Osteopathia Striata with Cranial Sclerosis

Search GEO for disease gene expression data for Osteopathia Striata with Cranial Sclerosis.

Pathways for Osteopathia Striata with Cranial Sclerosis

Pathways related to Osteopathia Striata with Cranial Sclerosis according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.54 LRP5 TGFBR1
2
Show member pathways
11.46 LRP5 TGFBR1
3 11.26 TGFBR1 TNFRSF11B
4 11.06 AMER1 LRP5 TGFBR1
5 10.61 TGFBR1 TNFRSF11B

GO Terms for Osteopathia Striata with Cranial Sclerosis

Cellular components related to Osteopathia Striata with Cranial Sclerosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 receptor complex GO:0043235 8.62 LRP5 TGFBR1

Biological processes related to Osteopathia Striata with Cranial Sclerosis according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 apoptotic process GO:0006915 9.54 TGFBR1 TNFRSF11B YARS
2 skeletal system development GO:0001501 9.4 TGFBR1 TNFRSF11B
3 anterior/posterior pattern specification GO:0009952 9.32 LRP5 TGFBR1
4 bone development GO:0060348 9.26 AMER1 LRP5
5 adipose tissue development GO:0060612 9.16 AMER1 LRP5
6 regulation of canonical Wnt signaling pathway GO:0060828 8.96 AMER1 LRP5
7 beta-catenin destruction complex disassembly GO:1904886 8.62 AMER1 LRP5

Sources for Osteopathia Striata with Cranial Sclerosis

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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