Malignant infantile osteopetrosis is a rare osteosclerosing type of

skeletal dysplasia Osteochondrodysplasia is a general term for a disorder of the development (dysplasia) of bone ("osteo") and cartilage ("chondro"). Osteochondrodysplasias are rare diseases. About 1 in 5,000 babies are born with some type of skeletal dysplasia. Non ...

that typically presents in infancy and is characterized by a unique radiographic appearance of generalized

hyperostosis Hyperostosis is an excessive growth of bone. It may lead to exostosis. It occurs in many musculoskeletal disorders. See also * Diffuse idiopathic skeletal hyperostosis * Hyperostosis frontalis interna * Infantile cortical hyperostosis * Porotic ...

(excessive growth of bone). The generalized increase in bone density has a special predilection to involve the medullary portion with relative sparing of the cortices.EL-Sobky TA, Elsobky E, Sadek I, Elsayed SM, Khattab MF (2016)
"A case of infantile osteopetrosis: The radioclinical features with literature update'
''Bone Rep''. 4:11-16
doi:10.1016/j.bonr.2015.11.002PMC 4926827
Obliteration of bone marrow spaces and subsequent depression of the cellular function can result in serious hematologic complications. Optic atrophy and cranial nerve damage secondary to bony expansion can result in marked morbidity. The prognosis is extremely poor in untreated cases.Orchard PJ, Fasth AL, Le Rademacher J, et al (2015)
"Hematopoietic stem cell transplantation for infantile osteopetrosis"
''Blood''. 126:270–6
DOI: 10.1182/blood-2015-01-625541. PMC 4497967
Plain radiography provides the key information to the diagnosis. Clinical and radiologic correlations are also fundamental to the diagnostic process, with additional gene testing being confirmatory.

Presentation

Hematologic manifestations related to bone marrow suppression and subsequent pancytopenia are a major source of morbidity and mortality. Additionally, extramedullary hematopoiesis can result in liver and spleen dysfunction. Cranial nerve dysfunction and neurologic complications are usually associated with infantile osteopetrosis. Expansion of the skull bone leads to

macrocephaly Macrocephaly is a condition in which circumference of the human head is abnormally large. It may be pathological or harmless, and can be a familial genetic characteristic. People diagnosed with macrocephaly will receive further medical tests to ...

. Additionally, linear growth retardation that is not apparent at birth, delayed motor milestones and poor dentition can occur.

Diagnosis

Skeletal radiography

The generalized increase in bone density of the medullary portion predominates with relative sparing of the cortices. The axial and appendicular skeleton are uniformly involved. Malignant infantile osteopetrosis is known for exhibiting specific plain radiographic abnormalities: * Loss of differentiation between the medullary and cortical portions of bone is a radiographic hallmark of infantile osteopetrosis * Characteristic endobone or "bone-within-bone" appearance in the spine, or "sandwich vertebra" appearance, characterized by dense endplate sclerosis with sharp margins * Characteristic endobone or "bone-within-bone" appearance in the pelvis and long bones of extremities where areas of osteosclerosis intermingle with areas of relatively hypodense bone. * Failure of

remodeling Renovation (also called remodeling) is the process of improving broken, damaged, or outdated structures. Renovations are typically done on either commercial or residential buildings. Additionally, renovation can refer to making something new, ...

of the distal femoral and proximal humeral metaphyses giving the affected bones a funnel shaped appearance known as an Erlenmeyer flask deformity * Alternating radiolucent femoral metaphyseal bands *

Pathologic fracture A pathologic fracture is a bone fracture caused by weakness of the bone structure that leads to decrease mechanical resistance to normal mechanical loads. This process is most commonly due to osteoporosis, but may also be due to other pathologies ...

Differential diagnosis

The differential diagnosis of malignant infantile osteopetrosis includes other genetic

s that cause

osteosclerosis Osteosclerosis is a disorder that is characterized by abnormal hardening of bone and an elevation in bone density. It may predominantly affect the medullary portion and/or cortex of bone. Plain radiographs are a valuable tool for detecting and ...

. They are collectively known as osteosclerosing dysplasias. The differential diagnosis of genetic osteosclerosing dysplasias including infantile osteopetrosis has been tabulated and illustrated in literature citations.Ihde LL, Forrester DM, Gottsegen CJ, Masih S, Patel DB, Vachon LA, et al. (2011)
"Sclerosing bone dysplasias: Review and differentiation from other causes of osteosclerosis"
''RadioGraphics''. 31:7, 1865-82. DOI: https://dx.doi.org/10.1148/rg.317115093 * Neuropathic infantile osteopetrosis * Infantile osteopetrosis with renal tubular acidosis * Infantile osteopetrosis with immunodeficiency * IO with leukocyte adhesion deficiency syndrome (LAD-III) * Intermediate osteopetrosis * Autosomal dominant osteopetrosis (Albers-Schonberg) * Pyknodysostosis (osteopetrosis acro-osteolytica) *

Osteopoikilosis Osteopoikilosis is a benign, autosomal dominant sclerosing dysplasia of bone characterized by the presence of numerous bone islands in the skeleton. Presentation The radiographic appearance of osteopoikilosis on an X-ray is characterized by a patt ...

(Buschke–Ollendorff syndrome) *

Osteopathia striata Osteopathia striata is a rare entity characterized by fine linear striations about 2- to 3-mm-thick, visible by radiographic examination, in the metaphyses and diaphyses of long or flat bones. It is often asymptomatic, and is often discovered incid ...

with cranial sclerosis * Mixed sclerosing bone dysplasia * Progressive diaphyseal dysplasia (

Camurati–Engelmann disease Camurati–Engelmann disease (CED) is a very rare autosomal dominant genetic disorder that causes characteristic anomalies in the skeleton. It is also known as progressive diaphyseal dysplasia. It is a form of dysplasia. Patients typically have ...

) * SOST-related sclerosing bone dysplasias

Treatment

The only effective line of treatment for malignant infantile osteopetrosis is

hematopoietic stem cell transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produc ...

.EL-Sobky TA, El-Haddad A, Elsobky E, Elsayed SM, Sakr HM (2017)
“Reversal of skeletal radiographic pathology in a case of malignant infantile osteopetrosis following hematopoietic stem cell transplantation”
''Egypt J Radiol Nucl Med''. 48 (1):237–43. http://doi.org/10.1016/j.ejrnm.2016.12.013.Costelloe CM, Eftekhari F, Petropoulos D (2007)
"Radiography of successful bone marrow transplantation for osteopetrosis"
''Skeletal Radiol''. 36:S34–S37
DOI: 10.1007/s00256-006-0141-1
/ref> It has been shown to provide long-term disease-free periods for a significant percentage of those treated. It can impact both hematologic and skeletal abnormalities; and has been used successfully to reverse the associated skeletal abnormalities. Radiographs of at least one case with malignant infantile osteopetrosis have demonstrated bone remodeling and recanalization of medullar canals following hematopoietic stem cell transplantation. This favorable radiographic response could be expected within one year following the procedure – nevertheless, primary graft failure can prove fatal.

References

External links

{{Medical resources , ICD10 = Q78.2 , ICD9 = , ICDO = , OMIM = , DiseasesDB = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeSH = , GeneReviewsNBK = , GeneReviewsName = , Orphanet = 667 Skeletal disorders Rare diseases