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Blomstrand lethal chondrodysplasia
Disease definition
Blomstrand lethal chondrodysplasia (BLC) is a neonatal osteosclerotic dysplasia characterized by advanced endochondral bone maturation, very short limbs, dwarfism and prenatal lethality.
ORPHA:50945
Classification level: Disorder- Synonym(s):
- BLC
- BOCD
- Blomstrand chondrodysplasia
- Blomstrand osteochondrodysplasia
- Chondrodysplasia, Blomstrand type
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal recessive
- Age of onset: Antenatal, Neonatal
- ICD-10: Q78.8
- ICD-11: LD24.1Y
- OMIM: 215045
- UMLS: C1859148
- MeSH: C537914
- GARD: 914
- MedDRA: -
Summary
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, 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 and a fetus with very short limbs, nuchal edema, 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% risk of having an affected child.
Prognosis
Both forms of BLC are lethal either prenatally or shortly after birth.
A summary on this disease is available in Deutsch (2005) Français (2005) Español (2014) Nederlands (2014)
Additional information