MCID: OST022
MIFTS: 47

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 57 12 75 37 29 13 6 15 40
Hyperostosis Generalisata with Striations 57 12 53 59 75
Robinow-Unger Syndrome 12 53 59 75
Osteopathia Striata Cranial Sclerosis 53 44 73
Oscs 57 53 75
Osteopathia Striata-Cranial Sclerosis Syndrome 53 59
Osteopathia Striata - Cranial Sclerosis 53
Voorhoeve Disease 53

Characteristics:

Orphanet epidemiological data:

59
osteopathia striata-cranial sclerosis syndrome
Inheritance: X-linked dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
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


Classifications:



Summaries for Osteopathia Striata with Cranial Sclerosis

OMIM : 57 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 wilms tumor 5, and has symptoms including apnea and headache. 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 macrocephaly and low-set ears

UniProtKB/Swiss-Prot : 75 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 : 53 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.

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 16)
# Related Disease Score Top Affiliating Genes
1 hyperostosis 29.6 LRP5 TNFRSF11B
2 wilms tumor 5 10.2
3 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.2
4 wilms tumor 6 10.2
5 spinal stenosis 10.2
6 osteomyelitis 10.2
7 cervicitis 10.2
8 hepatoblastoma 10.2
9 47, xxy 10.2
10 celiac disease 1 9.9
11 anxiety 9.9
12 bone resorption disease 9.7 LRP5 TNFRSF11B
13 bone remodeling disease 9.7 LRP5 TNFRSF11B
14 bone disease 9.2 LRP5 TNFRSF11B
15 endosteal hyperostosis, autosomal dominant 9.2 AMER1 LRP5 TNFRSF11B
16 osteoporosis 8.5 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:

57
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 Ribs Sternum 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 Gastrointestinal:
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:

59 32 (show all 45)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 59 32 frequent (33%) Frequent (79-30%) HP:0000256
2 low-set ears 59 32 occasional (7.5%) Occasional (29-5%) HP:0000369
3 frontal bossing 59 32 frequent (33%) Frequent (79-30%) HP:0002007
4 intellectual disability 59 32 occasional (7.5%) Occasional (29-5%) HP:0001249
5 dysphasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002357
6 cerebral calcification 59 32 occasional (7.5%) Occasional (29-5%) HP:0002514
7 scoliosis 59 32 frequent (33%) Frequent (79-30%) HP:0002650
8 hyperlordosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0003307
9 facial palsy 59 32 occasional (7.5%) Occasional (29-5%) HP:0010628
10 cataract 59 32 occasional (7.5%) Occasional (29-5%) HP:0000518
11 global developmental delay 59 32 occasional (7.5%) Occasional (29-5%) HP:0001263
12 wide nasal bridge 59 32 frequent (33%) Frequent (79-30%) HP:0000431
13 thickened calvaria 59 32 hallmark (90%) Very frequent (99-80%) HP:0002684
14 brachycephaly 59 32 occasional (7.5%) Occasional (29-5%) HP:0000248
15 prominent forehead 59 32 frequent (33%) Frequent (79-30%) HP:0011220
16 micrognathia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000347
17 abnormality of the metaphysis 59 32 hallmark (90%) Very frequent (99-80%) HP:0000944
18 retrognathia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000278
19 delayed eruption of teeth 59 32 frequent (33%) Frequent (79-30%) HP:0000684
20 epicanthus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000286
21 large iliac wings 59 32 hallmark (90%) Very frequent (99-80%) HP:0008818
22 flat face 59 32 occasional (7.5%) Occasional (29-5%) HP:0012368
23 specific learning disability 59 32 occasional (7.5%) Occasional (29-5%) HP:0001328
24 high, narrow palate 59 32 frequent (33%) Frequent (79-30%) HP:0002705
25 coarctation of aorta 59 32 occasional (7.5%) Occasional (29-5%) HP:0001680
26 aphasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0002381
27 conductive hearing impairment 59 32 frequent (33%) Frequent (79-30%) HP:0000405
28 flat occiput 59 32 frequent (33%) Frequent (79-30%) HP:0005469
29 severe short stature 59 32 occasional (7.5%) Occasional (29-5%) HP:0003510
30 spina bifida occulta 59 32 occasional (7.5%) Occasional (29-5%) HP:0003298
31 large fontanelles 59 32 frequent (33%) Frequent (79-30%) HP:0000239
32 bifid uvula 59 32 frequent (33%) Frequent (79-30%) HP:0000193
33 aortic valve stenosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0001650
34 rough bone trabeculation 59 32 hallmark (90%) Very frequent (99-80%) HP:0100670
35 submucous cleft hard palate 59 32 frequent (33%) Frequent (79-30%) HP:0000176
36 delayed cranial suture closure 59 32 frequent (33%) Frequent (79-30%) HP:0000270
37 osteopetrosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0011002
38 asymmetry of the thorax 59 32 occasional (7.5%) Occasional (29-5%) HP:0001555
39 posteriorly rotated ears 59 32 occasional (7.5%) Occasional (29-5%) HP:0000358
40 echolalia 59 32 occasional (7.5%) Occasional (29-5%) HP:0010529
41 mutism 59 32 occasional (7.5%) Occasional (29-5%) HP:0002300
42 facial hyperostosis 59 32 hallmark (90%) Very frequent (99-80%) HP:0005465
43 high iliac wings 59 32 hallmark (90%) Very frequent (99-80%) HP:0008808
44 cleft palate 59 Frequent (79-30%)
45 increased bone mineral density 59 Very frequent (99-80%)

UMLS symptoms related to Osteopathia Striata with Cranial Sclerosis:


apnea, headache

MGI Mouse Phenotypes related to Osteopathia Striata with Cranial Sclerosis:

46
# 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 29 AMER1

Anatomical Context for Osteopathia Striata with Cranial Sclerosis

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

41
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
Male child with somatic mosaic Osteopathia Striata with Cranial Sclerosis caused by a novel pathogenic AMER1 frameshift mutation. ( 28497491 )
2017
3
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
4
A Case Study of a Preadolescent With Osteopathia Striata With Cranial Sclerosis. ( 28390856 )
2017
5
Novel AMER1 frameshift mutation in a girl with osteopathia striata with cranial sclerosis. ( 28990699 )
2017
6
Osteopathia striata with cranial sclerosis and Wilms tumor: Coincidence or consequence? ( 29120061 )
2017
7
Germline mosaicism in osteopathia striata with cranial sclerosis - recurrence in siblings. ( 26886897 )
2016
8
First case of osteopathia striata with cranial sclerosis in an adult male with Klinefelter syndrome. ( 27369646 )
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
Osteomyelitis in an Osteopathia Striata with Cranial Sclerosis Patient. ( 27489848 )
2014
13
A novel WTX mutation in a female patient with osteopathia striata with cranial sclerosis and hepatoblastoma. ( 24459086 )
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
Osteopathia striata with cranial sclerosis owing to WTX gene defect. ( 20209645 )
2010
19
Mosaicism in osteopathia striata with cranial sclerosis. ( 20150574 )
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
How to counsel in osteopathia striata with cranial sclerosis. ( 9327263 )
1997
30
Osteopathia striata with cranial sclerosis: highly variable phenotypic expression within a family. ( 9383023 )
1997

Variations for Osteopathia Striata with Cranial Sclerosis

ClinVar genetic disease variations for Osteopathia Striata with Cranial Sclerosis:

6
(show all 15)
# Gene Variation Type Significance SNP ID Assembly Location
1 AMER1 AMER1, DEL deletion Pathogenic
2 AMER1 AMER1, 1-BP DEL, 671C deletion Pathogenic
3 AMER1 AMER1, 1-BP INS, 780A insertion 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.1057C> T (p.Arg353Ter) single nucleotide variant Pathogenic rs137852216 GRCh38 Chromosome X, 64192230: 64192230
6 AMER1 NM_152424.3(AMER1): c.1072C> T (p.Arg358Ter) single nucleotide variant Pathogenic rs137852217 GRCh37 Chromosome X, 63412095: 63412095
7 AMER1 NM_152424.3(AMER1): c.1072C> T (p.Arg358Ter) single nucleotide variant Pathogenic rs137852217 GRCh38 Chromosome X, 64192215: 64192215
8 AMER1 NM_152424.3(AMER1): c.429T> A (p.Cys143Ter) single nucleotide variant Pathogenic rs387906722 GRCh37 Chromosome X, 63412738: 63412738
9 AMER1 NM_152424.3(AMER1): c.429T> A (p.Cys143Ter) single nucleotide variant Pathogenic rs387906722 GRCh38 Chromosome X, 64192858: 64192858
10 AMER1 NM_152424.3(AMER1): c.1267delC (p.Leu423Trpfs) deletion Pathogenic rs398122877 GRCh37 Chromosome X, 63411900: 63411900
11 AMER1 NM_152424.3(AMER1): c.1267delC (p.Leu423Trpfs) deletion Pathogenic rs398122877 GRCh38 Chromosome X, 64192020: 64192020
12 AMER1 NM_152424.3(AMER1): c.811C> T (p.Gln271Ter) single nucleotide variant Pathogenic rs387907269 GRCh37 Chromosome X, 63412356: 63412356
13 AMER1 NM_152424.3(AMER1): c.811C> T (p.Gln271Ter) single nucleotide variant Pathogenic rs387907269 GRCh38 Chromosome X, 64192476: 64192476
14 AMER1 NM_152424.3(AMER1): c.655delG (p.Glu219Argfs) deletion Likely pathogenic GRCh38 Chromosome X, 64192632: 64192632
15 AMER1 NM_152424.3(AMER1): c.655delG (p.Glu219Argfs) deletion Likely pathogenic GRCh37 Chromosome X, 63412512: 63412512

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 regulation of canonical Wnt signaling pathway GO:0060828 9.16 AMER1 LRP5
6 adipose tissue development GO:0060612 8.96 AMER1 LRP5
7 beta-catenin destruction complex disassembly GO:1904886 8.62 AMER1 LRP5

Sources for Osteopathia Striata with Cranial Sclerosis

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19 FMA
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45 MESH via Orphanet
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69 SNOMED-CT via HPO
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74 UMLS via Orphanet
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