Otologic Manifestations of Malignant Osteopetrosis

Dozier, Thomas S.; Duncan, Irenee M; Klein, Alan J.; Lambert, Paul R.; Key, L. Lyndon

doi:10.1097/01.mao.0000178139.27472.8d

Cited by 47 publications

(31 citation statements)

References 12 publications

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“…The abnormally thickened bone can cause narrow cranial nerves foramina resulting in facial palsy, deafness, and blindness [13]. Primary seizures with normal calcium levels, hypotonia, developmental delay, retinal atrophy, and sensorineural deafness are signs of primary neurodegeneration that appear in some patients with ARO variants (neuropathic ARO) [13].…”

Section: Discussionmentioning

confidence: 99%

Malignant Infantile Osteopetrosis: A Case Report

Bubshait¹,

Fadaaq²,

Alshmas³

2020

Cureus

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Section: Discussionmentioning

confidence: 99%

Malignant Infantile Osteopetrosis: A Case Report

Bubshait¹,

Fadaaq²,

Alshmas³

2020

Cureus

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“…The expanding bones encroach on nerve foramina leading to blindness, deafness, and facial palsy 1. Complete visual loss occurs invariably in all untreated patients and hearing loss is estimated to affect 78% of individuals with OP 2. Tooth eruption defects and severe dental caries are common 3.…”

Section: Introductionmentioning

confidence: 99%

AnSNX10mutation causes malignant osteopetrosis of infancy

et al. 2012

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Background Osteopetrosis is a life-threatening, rare disorder typically resulting from osteoclast dysfunction and infrequently from failure to commitment to osteoclast lineage. Patients commonly present in infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, and bone marrow failure. In w70% of the patients there is a molecularly defined failure to maintain an acid pH at the osteoclast-bone interface (the ruffled border) which is necessary for the bone resorptive activity. Methods and resultsIn eight patients with infantile osteopetrosis which could be cured by bone marrow transplantation, the study identified by homozygosity mapping in distantly related consanguineous pedigrees a missense mutation in a highly conserved residue in the SNX10 gene. The mutation segregated with the disease in the families and was carried by one of 211 anonymous individuals of the same ethnicity. In the patients' osteoclasts, the mutant SNX10 protein was abnormally abundant and its distribution altered. The patients' osteoclasts were fewer and smaller than control cells, their resorptive capacity was markedly deranged, and the endosomal pathway was perturbed as evidenced by the distribution of internalised dextran. Conclusions SNX10 was recently shown to interact with vacuolar type H + -ATPase (V-ATPase) which pumps protons at the osteoclast-bone interface. Mutations in TCIRG1, the gene encoding a subunit of the V-ATPase complex, account for the majority of cases of osteopetrosis. It is speculated that SNX10 is responsible for the vesicular sorting of V-ATPase from Golgi or for its targeting to the ruffled border. A mutation in SNX10 may therefore result in 'secondary V-ATPase deficiency' with a failure to acidify the resorption lacuna. Determination of the sequence of the SNX10 gene is warranted in molecularly undefined patients with recessive 'pure' osteopetrosis of infancy.

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“…It occurs early in life and represents a life threatening condition. 3,10 It is due to the decrease of bone remodeling leading to choanal obstruction 3,11 confirmed by computed tomography in the two first cases. A few cases of ARO revealed by choanal imperforation were reported in the literature.…”

Section: Discussionmentioning

confidence: 92%

Clinical and imaging features of malignant infantile osteopetrosis

Tfifha¹,

Gaha²,

Gamaoun³

et al. 2017

Turk J Pediatr

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Tfifha M, Gaha M, Gamaoun W, Chemli J, Mabrouk S, Hassayoun S, Zouari N, Jemni H, Abroug S. Clinical and imaging features of malignant infantile osteopetrosis. Turk J Pediatr 2017; 59: 452-457. Human osteopetrosis is a rare genetic disorder caused by osteoclast failure. It encompasses a group of highly heterogeneous forms, ranged widely in severity. Patients with autosomal recessive osteopetrosis are the most severely affected osteopetrotic patients. Here we describe Tunisian children with severe phenotype. They are native from the same geographic region, born to consanguineous parents. Clinical features were cranio-facial dysmorphy, macrocephaly, hepatosplenomegaly, severe anemia and thrombocytopenia with precocious onset of neuronopathic complications, blindness and deafness. Retinal atrophy, reported in a minority of forms is highlighted. Skeletal radiographs revealed generalized increase in bone density and abnormal metaphyseal remodeling, and superimposed rickets resulting from the defect in osteoclasts to provide a normal Ca/P balance. We report an exceptional association with congenital hypothyroidism. Multi-organ failure due to sepsis is one the most severe complications observed. The issue was fatal without hematopoietic stem cell transplantation.

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Otologic Manifestations of Malignant Osteopetrosis

Abstract: Otologic manifestations are common in malignant osteopetrosis secondary to the formation of dense, brittle bone. Frequent findings include external auditory canal stenosis, otitis media, conductive and sensorineural hearing loss, and facial nerve paralysis.

Cited by 47 publications

References 12 publications

Malignant Infantile Osteopetrosis: A Case Report

Malignant Infantile Osteopetrosis: A Case Report

AnSNX10mutation causes malignant osteopetrosis of infancy

Clinical and imaging features of malignant infantile osteopetrosis

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