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Disease Profile

Osteopathia striata with cranial sclerosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

Q78.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

OSCS; Hyperostosis generalisata with striations; Osteopathia striata cranial sclerosis;

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases

Summary

Osteopathia striata with cranial sclerosis (OSCS) causes the bones to become unusually hard and thick. The severity of the condition and the symptoms vary significantly from person to person, even within the same family. Features of the condition are generally present at birth. Symptoms may include skeletal abnormalities at the ends of long bones, hardening (sclerosis) of the bones of the head and face, large head size, and cleft palate. Some people with OSCS may also have developmental delay, hearing loss, heart defects, and breathing and feeding difficulties. Osteopathia striata cranial sclerosis is caused by variants in the AMER1 gene and is inherited in an X-linked dominant pattern. Diagnosis is based on the symptoms, clinical exam, and may be confirmed by the results of genetic testing. Treatment is focused on managing the symptoms and may include surgery and physical therapy.[1][2]

Symptoms

The following list includes the most common signs and symptoms in people with osteopathia striata with cranial sclerosis (OSCS). These features may be different from person to person. Some people may have more symptoms than others, and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

The symptoms in females with OSCS can range from very mild to severe. Males with OSCS usually (but not always) have very severe symptoms and die before or shortly after birth.[3]

Symptoms of OSCS may include:[4][5985]

  • Abnormal thickening of the bones (especially the long bones)
  • Large head size (macrocephaly)
  • Hardening of the bones of the head and face
  • Cleft palate
  • Hearing loss

Less common features include heart defects, gastrointestinal abnormalities, and developmental delay. About 100 cases of OSCS have been described in the literature, and there is not much information about how this condition may change as someone gets older. It is known that people with OSCS may be shorter than average, have delayed eruption of teeth, and may be at increased risk to develop Wilm's tumor.[5]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Coarse metaphyseal trabecularization
0100670
Facial hyperostosis
Enlargment of the facial bones
Excessive growth of facial bones
Excessive growth of facial skeleton
Increase in size of the facial bones
Overgrowth of facial bones
Overgrowth of facial skeleton
Overgrowth of the facial bones

[ more ]

0005465
Growth hormone excess
0000845
High iliac wings
0008808
Increased circulating prolactin concentration
0000870
Increased serum insulin-like growth factor 1
0030269
Large iliac wings
0008818
Osteopetrosis
Harder, denser, fracture-prone bones
0011002
Tall stature
Increased body height
0000098
Thickened calvaria
Increased thickness of skull cap
Thickened skull cap

[ more ]

0002684
30%-79% of people have these symptoms
Abnormal oral glucose tolerance
0004924
Abnormality of optic chiasm morphology
0025163
Bifid uvula
0000193
Coarse facial features
Coarse facial appearance
0000280
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

0000405
Decreased thyroid-stimulating hormone level
0031098
Delayed cranial suture closure
0000270
Delayed eruption of teeth
Delayed eruption
Delayed teeth eruption
Delayed tooth eruption
Eruption, delayed
Late eruption of teeth
Late tooth eruption

[ more ]

0000684
Fasting hyperinsulinemia
High blood insulin levels while fasting
0008283
Flat occiput
0005469
Frontal bossing
0002007
High, narrow palate
Narrow, high-arched roof of mouth
Narrow, highly arched roof of mouth

[ more ]

0002705
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased

[ more ]

0000975
Increased body mass index
0031418
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation

[ more ]

0001256
Large fontanelles
Wide fontanelles
0000239
Macrocephaly
Increased size of skull
Large head
Large head circumference

[ more ]

0000256
Pituitary adenoma
Noncancerous tumor in pituitary gland
0002893
Polyphagia
Voracious appetite
0002591
Prominent forehead
Pronounced forehead
Protruding forehead

[ more ]

0011220
Scoliosis
0002650
Sleep apnea
Pauses in breathing while sleeping
0010535
Snoring
0025267
Submucous cleft hard palate
0000176
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
5%-29% of people have these symptoms
Abdominal distention
Abdominal bloating
Abdominal swelling
Belly bloating
Bloating

[ more ]

0003270
Abnormality of the cardiovascular system
Cardiovascular abnormality
0001626
Abnormality of the skeletal system
Skeletal abnormalities
Skeletal anomalies

[ more ]

0000924
Acanthosis nigricans
Darkened and thickened skin
0000956
Adrenocorticotropic hormone deficiency
0011748
Aortic valve stenosis
Narrowing of aortic valve
0001650
Aphasia
Difficulty finding words
Losing words
Loss of words

[ more ]

0002381
Asymmetry of the thorax
Asymmetric chest
0001555
Ataxia
0001251
Brachycephaly
Short and broad skull
0000248
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Cerebral calcification
Abnormal deposits of calcium in the brain
0002514
Coarctation of aorta
Narrowing of aorta
Narrowing of the aorta

[ more ]

0001680
Delayed puberty
Delayed pubertal development
Delayed pubertal growth
Pubertal delay

[ more ]

0000823
Diabetes insipidus
0000873
Diastema
Gap between teeth
0000699
Dysphasia
0002357
Echolalia
Echoing another person's speech
0010529
Enlarged pituitary gland
0012505
Epicanthus
Eye folds
Promi

Cause

Osteopathia striata with cranial sclerosis occurs when the AMER1 gene (previously known as the WTX gene) is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.[4]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Organizations

    Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

    Organizations Supporting this Disease

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      In-Depth Information

      • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
      • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
      • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
      • PubMed is a searchable database of medical literature and lists journal articles that discuss Osteopathia striata with cranial sclerosis. Click on the link to view a sample search on this topic.

        References

        1. Osteopathia striata cranial sclerosis. Orphanet. October 2012; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2780.
        2. Quélin C1, Loget P, D'Hervé D, Fradin M, Milon J, Ferry M, Body-Bechou D, Tréguier C, Garcia Hoyos M, Odent S. Osteopathia striata with cranial sclerosis: when a fetal malformation syndrome reveals maternal pathology. Prenat Diagn. February 2015; 35(2):200-202.
        3. Zicari AM, Tarani L, Perotti D, Papetti L, Nicita F, Liberati N, et al. WTX R353X mutation in a family with osteopathia striata and cranial sclerosis (OS-CS): case report and literature review of the disease clinical, genetic and radiological features. Ital J Pediatr. Jun 20, 2012; 38:27:https://pubmed.ncbi.nlm.nih.gov/22716240/.
        4. Mi J, Parthasarathy P, Halliday BJ, Morgan T, Dean J, Nowaczyk MJM, et al. Deletion of Exon 1 in AMER1 in Osteopathia Striata with Cranial Sclerosis.. Genes (Basel). Nov 30, 2020; 11(12):1439. https://pubmed.ncbi.nlm.nih.gov/33265914/.
        5. Bach A, Mi J, Hunter M, Halliday BJ, García-Miñaúr S, Sperotto F, et al. Wilms tumor in patients with osteopathia striata with cranial sclerosis. Eur J Hum Genet. Sep 2, 2020; Epub ahead of print. https://pubmed.ncbi.nlm.nih.gov/32879452.
        6. Hague J, Delon I, Brugger K, Martin H, Sparnon L, Simonic I, et al. Male child with somatic mosaic Osteopathia Striata with Cranial Sclerosis caused by a novel pathogenic AMER1 frameshift mutation. Am J Med Genet A. Jul 2017; 173(7):1931-1935. https://pubmed.ncbi.nlm.nih.gov/28497491/.

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