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Disease Profile

Chondrodysplasia Blomstrand type

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

Antenatal

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)

BOCD; Blomstrand's lethal chondrodysplasia; Blomstrand lethal osteochondrodysplasia

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.
orphanet

Orpha Number: 50945

Definition
Blomstrand lethal chondrodysplasia (BLC) is a neonatal osteosclerotic dysplasia (see this term) characterized by advanced endochondral bone maturation, very short limbs, dwarfism and prenatal lethality.

Epidemiology
To date, less than 10 cases have been described in the literature.

Clinical description
BLC is a congenital disorder characterized by a low birth weight, facial dysmorphism (widely spaced and protruding eyes (which typically show cataract), depressed nasal bridge, short columella, long philtrum, macroglossia, protruding tongue, severe micrognathia), short trunk, narrow thorax and severe rhizo-meso-acromelic shortness of the limbs. Other anomalies also observed include tooth and mammary gland development defects, hypoplastic lungs, aorta coarctation (see this term), and bowel malrotation. Two forms of BCL, have been described: type I which is the severe, classical form and type II which has less severe features (such as absence of short trunk or, severely shortened arms but moderately shortened legs).

Etiology
BLC is caused by inactivating homozygous or compound heterozygous mutations in PTH1R (3p22-p21.1) which encodes the parathyroid hormone (PTH)/parathyroid-hormone-related peptide (PTHrP) receptor (PTH1R). These mutations result in the decrease in binding or response to PTH and PTHrP.

Diagnostic methods
Diagnosis is based on the clinical and radiological characteristics which show generalized increase in bone density with advanced ossification, severe shortness of the long bones with wide metaphyses and club-shaped distal ends, long narrow thorax, calcified hyoid bone and laryngeal cartilage and underdeveloped viscerocranium. Histopathological examination shows an important acceleration of the endochondral ossification in tubular bones, narrow cartilages of the epiphyses and large epiphyseal ossification centers. Diagnosis is confirmed by the genetic screening of PTH1R.

Differential diagnosis
Differential diagnosis includes primary failure of tooth eruption (see this term) and other lethal short limbed dwarfisms.

Antenatal diagnosis
Prenatal diagnosis is achieved by sonographic examination showing polyhydramnios, hydrops fetalis (see this term) and a fetus with very short limbs, nuchale dema, macroglossia, a protuberant abdomen, internal anomalies and markedly advanced endochondral bone formation.

Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% chance of having an affected child.

Prognosis
Both forms of BLC are lethal either prenatally or shortly after birth.

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
80%-99% of people have these symptoms
Abnormality of epiphysis morphology
Abnormal shape of end part of bone
0005930
Accelerated skeletal maturation
Advanced bone age
Early bone maturation

[ more ]

0005616
Aplastic clavicle
Absent collarbone
0006660
Broad clavicles
Broad collarbone
0000916
Cataract
Clouding of the lens of the eye
Cloudy lens

[ more ]

0000518
Depressed nasal bridge
Depressed bridge of nose
Flat bridge of nose
Flat nasal bridge
Flat, nasal bridge
Flattened nasal bridge
Low nasal bridge
Low nasal root

[ more ]

0005280
Distal shortening of limbs
Short outer part of limbs
0006402
Flared metaphysis
Flared wide portion of long bone
0003015
Increased bone mineral density
Increased bone density
0011001
Lethal skeletal dysplasia
Lethal dwarfism identifiable at birth
0005716
Low-set ears
Low set ears
Lowset ears

[ more ]

0000369
Malar flattening
Zygomatic flattening
0000272
Mesomelia
Disproportionately short middle portion of limb
0003027
Metaphyseal cupping
0003021
Micrognathia
Little lower jaw
Small jaw
Small lower jaw

[ more ]

0000347
Narrow chest
Low chest circumference
Narrow shoulders

[ more ]

0000774
Neonatal short-limb short stature
Short limb dwarfism recognizable at birth
Short-limb dwarfism identifiable at birth
Short-limbed dwarfism identifiable at birth

[ more ]

0008921
Platyspondyly
Flattened vertebrae
0000926
Polyhydramnios
High levels of amniotic fluid
0001561
Premature birth
Premature delivery of affected infants
Preterm delivery

[ more ]

0001622
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes

[ more ]

0000520
Protuberant abdomen
Belly sticks out
Extended belly

[ more ]

0001538
Pulmonary hypoplasia
Small lung
Underdeveloped lung

[ more ]

0002089
Rhizomelia
Disproportionately short upper portion of limb
0008905
Short nose
Decreased length of nose
Shortened nose

[ more ]

0003196
Short ribs
0000773
Short thorax
Shorter than typical length between neck and abdomen
0010306
Telecanthus
Corners of eye widely separated
0000506
30%-79% of people have these symptoms
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Bowing of the long bones
Bowed long bones
Bowing of long bones

[ more ]

0006487
Hydrops fetalis
0001789
Long philtrum
0000343
Natal tooth
Born with teeth
Teeth present at birth

[ more ]

0000695
Protruding tongue
Prominent tongue
Tongue sticking out of mouth

[ more ]

0010808
Short metacarpal
Shortened long bone of hand
0010049
Synostosis of joints
Fusion of joints
0100240
5%-29% of people have these symptoms
Coarctation of aorta
Narrowing of aorta
Narrowing of the aorta

[ more ]

0001680
Percent of people who have these symptoms is not available through HPO
Advanced ossification of carpal bones
0004233
Advanced tarsal ossification
0008108
Autosomal recessive inheritance
0000007
Generalized osteosclerosis
0005789
Laryngeal calcification
0008754
Micromelia
Smaller or shorter than typical limbs
0002983
Squared iliac bones
0003177
Stillbirth
Stillborn
0003826

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.

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.

Where to Start

  • Genetics Home Reference (GHR) contains information on Chondrodysplasia Blomstrand type. This website is maintained by the National Library of Medicine.

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 Chondrodysplasia Blomstrand type. Click on the link to view a sample search on this topic.