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Disease Profile

Gracile bone dysplasia

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

Neonatal

ICD-10

Q78.0

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.

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)

Skeletal dysplasia lethal with gracile bones; Osteocraniostenosis; Osteocraniosplenic syndrome;

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
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Orpha Number: 2763

Definition
Osteocraniostenosis is a lethal skeletal dysplasia characterized by a cloverleaf skull anomaly, facial dysmorphism, limb shortness, splenic hypo/aplasia and radiological anomalies including thin tubular bones with flared metaphyses and deficient calvarial mineralization.

Epidemiology
First described in 1989, less than 30 cases have been reported so far.

Clinical description
'This multiple congenital anomalies syndrome is characterized by dysmorphic features of the fetus and the newborn: the skull is misshapen, combining acrocephaly and cloverleaf deformity, fontanelles are very large; facial dysmorphism includes midface hypoplasia with telecanthus, short upturned nose, short philtrum, small inverted V-shaped mouth and low-set ears; limbs are also affected with bowed forearms, micromelia and acromicria with brachydactyly.'

Etiology
Etiology of osteocraniostenosis is not well known, but some histological findings report growth plate disorganization and adjacent diaphyseal ossification. Recently, heterozygous mutations of the FAM111A gene, encoding a protein of unknown function and responsible of some autosomal dominant forms of Kenny-Caffey syndrome (see this term) with hypothyroidism and slender and dense bone, have been identified in patients with osteocraniostenosis. A clinical and genetic heterogeneity remains likely.

Diagnostic methods
Diagnosis is based mainly on radiological and pathological examination. Radiological examination reveals hypomineralisation of the skull, flat and dense vertebral bodies, thin tubular bones with flared and dense metaphyses, brachymetacarpia and brachyphalangy with ''diabolo appearance'' (very thin tubular bones with abrupt metaphyseal flare) and lack of ossification of the distal phalanges. The spleen is hypoplasic or even absent. Diaphyseal fractures are frequent at birth.

Differential diagnosis
Differential diagnosis includes the hypo/akinesia sequence, Hallermann-Streiff-FranÁois syndrome, Kenny-Caffey syndrome and other slender bone dysplasias, and some cases of osteogenesis imperfecta with slender bones (see these terms).

Antenatal diagnosis
Prenatal ultrasound observation reveals micromelic dwarfism, cranial deformity, mild intra-uterine growth retardation and sometimes fractures.

Genetic counseling
Cases with FAM111A gene mutations show an autosomal dominant mode of inheritance with a majority of de novo mutations.

Management and treatment
There is no treatment for osteocraniostenosis.

Prognosis
Prognosis is very poor as most cases are stillborn or die in their first days of life.

Visit the Orphanet disease page for more resources.

Symptoms

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
5%-29% of people have these symptoms
Asplenia
Absent spleen
0001746
Decreased skull ossification
Decreased bone formation of skull
0004331
Percent of people who have these symptoms is not available through HPO
Aniridia
Absent iris
0000526
Ankyloglossia
Tongue tied
0010296
Ascites
Accumulation of fluid in the abdomen
0001541
Autosomal dominant inheritance
0000006
Brachydactyly
Short fingers or toes
0001156
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Flared metaphysis
Flared wide portion of long bone
0003015
Global developmental delay
0001263
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hypocalcemia
Low blood calcium levels
0002901
Hypoplastic spleen
Underdeveloped spleen
0006270
Micropenis
Short penis
Small penis

[ more ]

0000054
Microphthalmia
Abnormally small eyeball
0000568
Prominent forehead
Pronounced forehead
Protruding forehead

[ more ]

0011220
Seizure
0001250
Short stature
Decreased body height
Small stature

[ more ]

0004322
Slender long bone
Long bones slender
Thin long bones

[ more ]

0003100
Thin ribs
Slender ribs
0000883

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 Gracile bone dysplasia. Click on the link to view a sample search on this topic.