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Interdisciplinary CompetenceMolecular Diagnostics
Know how in the analysis of genetic material.
For the benefit of patients.

IllnessOsteopetrosis, differential diagnosis

Summary

Short information

Comprehensive differential diagnostic panel for Osteopetrosis comprising 8 guideline-curated core genes and altogether 26 curated genes according to the clinical signs

ID
OP8642
Number of genes
22 Accredited laboratory test
Examined sequence length
20,2 kb (Core-/Core-canditate-Genes)
38,9 kb (Extended panel: incl. additional genes)
Analysis Duration
on request
Material
  • EDTA-anticoagulated blood (3-5 ml)
Diagnostic indications

NGS +

 

Gene panel

Selected genes

NameExon Length (bp)OMIM-GReferenz-Seq.Heredity
CA2783NM_000067.3AR
CLCN72418NM_001287.6AD, AR
FERMT31992NM_031471.6AR
LRP54848NM_002335.4AD
OSTM11005NM_014028.4AR
PLEKHM13171NM_014798.3AD, AR
SNX10606NM_001199835.1AR
TCIRG12493NM_006019.4AR
TNFRSF11A1851NM_003839.4AD, AR
TNFSF11954NM_003701.4AR
AMER13408NM_152424.4XL
ANKH1479NM_054027.6AD
CTSK990NM_000396.4AR
FAM20C1755NM_020223.4AR
GJA11149NM_000165.5AD, AR
LEMD32736NM_014319.5AD
PTH1R1782NM_000316.3AD, AR
RASGRP21830NM_153819.1AR
SLC29A31428NM_018344.6AR
SOST642NM_025237.3AD, AR
TGFB11173NM_000660.7AD
TYROBP309NM_001173514.2AR

Informations about the disease

Clinical Comment

Osteopetrosis causes abnormally high bone density, thus increasing also brittleness. Autosomal dominant osteopetrosis is usually the mildest form and sometimes completely asymptomatic, especially in young children. On the other hand, in late childhood or adolescence the main features in affected individuals include multiple fractures, scoliosis or other spinal abnormalities, hip osteoarthritis and osteomyelitis. Autosomal recessively inherited osteopetrosis causes a more severe form already in early childhood. Dense bone tissue constricts cranial nerves with paralysis of facial muscles, loss of vision and hearing, and can also lead to bone marrow suppression with anemia, hemorrhage and recurrent infections, the latter of which can be life-threatening in infancy or early childhood. In addition, slowed growth rates and small stature are observed as well as dental abnormalities and hepatosplenomegaly, sometimes also accompanied by brain malformations, intellectual disability or epilepsy. X-linked osteopetrosis is rare and, in addition to dense bone structure, lymphedema, anhydrotic ectodermal dysplasia and immunodeficiency are observed. Mutations in the CLCN7 gene are responsible for approximately 75% of autosomal dominant osteopetrosis cases, 10-15% of cases are inherited in an autosomal recessive manner. TCIRG1 mutations cause half of autosomal recessive osteopetrosis. The X-linked type is caused by mutations in the IKBKG gene. In less than one-third of all cases, the cause of the disease cannot be elucidated by molecular genetics, even when up to 25 associated genes are studied. The 70% yield rate implies that the clinical diagnosis cannot be refuted by a negative molecular genetic result.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1127/

 

Synonyms
  • Alias: Marble bone disease; Albers-Schonberg disease
  • Allelic: Bleeding disorder, platelet-type, 18 (RASGRP2)
  • Allelic: Bone mineral density variability 1 (LRP5)
  • Allelic: Coronary artery disease, autosomal dominant, 2 (LRP6)
  • Allelic: Exudative vitreoretinopathy 4 (LRP5)
  • Allelic: Hyperostosis, endosteal (LRP5)
  • Allelic: Hypopigmentation, organomegaly, delayed myelination + development (CLCN7)
  • Allelic: Leukoencephalopathy, diffuse hereditary, with spheroids 1 (CSF1R)
  • Allelic: Osteolysis, familial expansile (TNFRSF11A)
  • Allelic: Osteoporosis (LRP5)
  • Allelic: Osteoporosis-pseudoglioma syndrome (LRP5)
  • Allelic: Osteosclerosis (LRP5)
  • Allelic: Paget disease of bone 2, early-onset (TNFRSF11A)
  • Allelic: Polycystic liver disease 4 with/-out kidney cysts (LRP5)
  • Allelic: Tooth agenesis, selective, 7 (LRP6)
  • Allelic: van Buchem disease, type 2 (LRP5)
  • Brain abnormalities, neurodegeneration + dysosteosclerosis (CSF1R)
  • Chondrocalcinosis (ANKH)
  • Craniodiaphyseal dysplasia, AD (SOST)
  • Craniometaphyseal dysplasia (ANKH)
  • Craniometaphyseal dysplasia, AR (GJA1)
  • Endosteal hyperostosis [GeneReviews] (LRP6)
  • Histiocytosis-lymphadenopathy plus syndrome [dysosteosclerosis] (SLC29A3)
  • Leukocyte adhesion deficiency, type III (FERMT3)
  • Osteoclast-poor AR osteopetrosis
  • Osteopetrosis, AD 1 (LRP5)
  • Osteopetrosis, AD 2 (CLCN7)
  • Osteopetrosis, AD 3 (PLEKHM1)
  • Osteopetrosis, AR 1 (TCIRG1)
  • Osteopetrosis, AR 2 (TNFSF11)
  • Osteopetrosis, AR 3, with renal tubular acidosis (CA2)
  • Osteopetrosis, AR 4 (CLCN7)
  • Osteopetrosis, AR 5 (OSTM1)
  • Osteopetrosis, AR 6 (PLEKHM1)
  • Osteopetrosis, AR 7 (TNFRSF11A)
  • Osteopetrosis, AR 8 (SNX10)
  • Osteosclerotic metaphyseal dysplasia (LRRK1)
  • Pycnodysostosis (CTSK)
  • Sclerosteosis 1 (SOST)
  • Van Buchem disease [Hyperostosis corticalis generalisata] (SOST)
Heredity, heredity patterns etc.
  • AD
  • AR
  • XL
OMIM-Ps
  • Multiple OMIM-Ps
ICD10 Code

Bioinformatics and clinical interpretation

No text defined