What are the other Names for this Condition? (Also known as/Synonyms)

• BLC (Blomstrand Lethal Chondrodysplasia)
• Blomstrand Lethal Osteochondrodysplasia
• Chondrodysplasia, Blomstrand type

What is Blomstrand Lethal Chondrodysplasia? (Definition/Background Information)

• Blomstrand Lethal Chondrodysplasia (BLC) is a neonatal osteosclerotic dysplasia characterized by advanced endochondral bone maturation, very short limbs, dwarfism and prenatal lethality
• 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, 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). Both forms of BLC are lethal either prenatally or shortly after birth
• To date, less than 10 cases have been described in the literature

(Source: Blomstrand Lethal Chondrodysplasia; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Blomstrand Lethal Chondrodysplasia? (Age and Sex Distribution)

• Blomstrand Lethal Chondrodysplasia is an extremely rare congenital disorder. The presentation of symptoms may occur before or following the birth of the child
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Blomstrand Lethal Chondrodysplasia? (Predisposing Factors)

• A positive family history may be an important risk factor, since Blomstrand Lethal Chondrodysplasia is an inherited condition
• Currently, no other risk factors have been clearly identified for BLC

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Blomstrand Lethal Chondrodysplasia? (Etiology)

• Blomstrand Lethal Chondrodysplasia 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
• 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

(Source: Blomstrand Lethal Chondrodysplasia; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Blomstrand Lethal Chondrodysplasia?

The signs and symptoms of Blomstrand Lethal Chondrodysplasia may include:

• Advanced ossification of carpal bones
• Advanced tarsal ossification
• Generalized osteosclerosis
• Laryngeal calcification
• Micromelia
• Squared iliac bones

Based on the frequency of symptoms observed, the following information may be noted:

Very frequently present symptoms in 80-99% of the cases:

• Abnormality of epiphysis morphology
• Accelerated skeletal maturation
• Aplastic clavicles
• Broad clavicles
• Cataract
• Distal shortening of limbs
• Flared metaphysis
• Increased bone mineral density
• Lethal skeletal dysplasia
• Low-set ears
• Malar flattening
• Mesomelia
• Metaphyseal cupping
• Micrognathia
• Narrow chest
• Neonatal short-limb short stature
• Platyspondyly
• Polyhydramnios
• Premature birth
• Proptosis
• Protuberant abdomen
• Pulmonary hypoplasia
• Rhizomelia
• Short nose
• Short ribs
• Short thorax
• Telecanthus

Frequently present symptoms in 30-79% of the cases:

• Anteverted nares 
• Bowing of the long bones 
• Hydrops fetalis 
• Long philtrum 
• Natal tooth 
• Protruding tongue
• Short metacarpal 
• Synostosis of joints

Occasionally present symptoms in 5-29% of the cases: 

• Coarctation of aorta

(Source: Blomstrand Lethal Chondrodysplasia; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Blomstrand Lethal Chondrodysplasia Diagnosed?

• Diagnosis of Blomstrand Lethal Chondrodysplasia 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 includes primary failure of tooth eruption (see this term) and other lethal short limbed dwarfisms
• Prenatal diagnosis is achieved by sonographic examination showing polyhydramnios, hydrops fetalis and a fetus with very short limbs, nuchale dema, macroglossia, a protuberant abdomen, internal anomalies and markedly advanced endochondral bone formation

(Source: Blomstrand Lethal Chondrodysplasia; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Blomstrand Lethal Chondrodysplasia?

The complications of Blomstrand Lethal Chondrodysplasia may include:

• Multiple abnormalities affecting many body parts and systems
• Stillbirth

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Blomstrand Lethal Chondrodysplasia Treated?

There is no cure for Blomstrand Lethal Chondrodysplasia, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops.

How can Blomstrand Lethal Chondrodysplasia be Prevented?

Currently, Blomstrand Lethal Chondrodysplasia may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Blomstrand Lethal Chondrodysplasia? (Outcomes/Resolutions)

• The prognosis of Blomstrand Lethal Chondrodysplasia is dependent upon the severity of the signs and symptoms and associated complications, if any
• However, typically, the prognosis is extremely poor for both types (I and II) of BLC

Additional and Relevant Useful Information for Blomstrand Lethal Chondrodysplasia:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/