# Osteopetrose

> Página oficial: https://raras.org/doenca/osteopetrose
> Fonte: Raras.org — Banco de Dados de Doenças Raras em Português (CC BY-NC-SA 4.0)
> Última atualização: 2026-05-07

## Identificadores

- **ORPHA**: 2781 — https://www.orpha.net/en/disease/detail/2781
- **CID-10**: Q78.2
- **OMIM**: none — https://omim.org/entry/none

## Descrição clínica

A osteopetrose ("doença esquelética marmórea") é um termo descritivo que se refere a um grupo de doenças hereditárias raras do esqueleto caracterizadas por densidade óssea aumentada na radiografia.

## Epidemiologia e herança

- **Prevalência**: Unknown
- **Padrão de herança**: Autosomal dominant, Autosomal recessive, X-linked recessive

## Sinais e sintomas (401 fenótipos HPO)

- **Bossas frontais** — HPO: HP:0002007
- **Rizomelia** — HPO: HP:0008905
- **Laringomalácia** — HPO: HP:0001601
- **Anormalidade da clavícula** — HPO: HP:0000889
- **Dedo curto** — HPO: HP:0009381
- **Pé curto** — HPO: HP:0001773
- **Fator de crescimento semelhante à insulina 1 sérico diminuído** — HPO: HP:0030353
- **Hipermobilidade articular** — HPO: HP:0001382
- **Dismielinização cerebral** — HPO: HP:0007266
- **Craniossinostose coronal** — HPO: HP:0004440
- **Anormalidade da refração** — HPO: HP:0000539
- **Sobrepeso** — HPO: HP:0025502
- **Atraso global leve do desenvolvimento** — HPO: HP:0011342
- **Asa ilíaca hipoplásica** — HPO: HP:0002866
- **Resposta diminuída ao teste de estímulo do hormônio do crescimento** — HPO: HP:0000824
- **Hipoplasia da maxila** — HPO: HP:0000327
- **Baixa estatura desproporcional de membros curtos** — HPO: HP:0008873
- **Pneumatização atrasada do processo mastoide** — HPO: HP:0005906
- **Hipoplasia do esmalte** — HPO: HP:0006297
- **Mesomelia** — HPO: HP:0003027
- **Displasia ungueal** — HPO: HP:0002164
- **Mão pequena** — HPO: HP:0200055
- **Dor crônica** — HPO: HP:0012532
- **Morfologia anormal da unha** — HPO: HP:0001597
- **Dorso nasal convexo** — HPO: HP:0000444
- **Malformação de Chiari** — HPO: HP:0002308
- **Acromelia** — HPO: HP:0010884
- **Estridor** — HPO: HP:0010307
- **Retardo do crescimento intrauterino** — HPO: HP:0001511
- **Aumento da pressão intracraniana** — HPO: HP:0002516
- **Disfunção do neurônio motor superior** — HPO: HP:0002493
- **Estrabismo** — HPO: HP:0000486
- **Retrusão médio-facial** — HPO: HP:0011800
- **Deficiência auditiva condutiva leve** — HPO: HP:0008598
- **Ângulo obtuso da mandíbula** — HPO: HP:0005446
- **Palidez** — HPO: HP:0000980
- **Suscetibilidade a hematomas** — HPO: HP:0000978
- **Morfologia anormal da costela** — HPO: HP:0000772
- **Polidrâmnio** — HPO: HP:0001561
- **Hélice superdobrada** — HPO: HP:0000396
- _...e mais 361 sintomas. Ver https://raras.org/doenca/osteopetrose._

## Genes associados (19)

- **FERMT3** — Fermitin family homolog 3 [Disease-causing germline mutation(s) in]
  - Função: Plays a central role in cell adhesion in hematopoietic cells (PubMed:19234463, PubMed:26359933). Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3) (By similarity). Required for integri
- **CTNNB1** — Catenin beta-1 [Candidate gene tested in]
  - Função: Key downstream component of the canonical Wnt signaling pathway (PubMed:17524503, PubMed:18077326, PubMed:18086858, PubMed:18957423, PubMed:21262353, PubMed:22155184, PubMed:22647378, PubMed:22699938)
- **IKBKG** — NF-kappa-B essential modulator [Candidate gene tested in]
  - Função: Regulatory subunit of the IKK core complex which phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhi
- **CSF1R** — Macrophage colony-stimulating factor 1 receptor [Candidate gene tested in]
  - Função: Tyrosine-protein kinase that acts as a cell-surface receptor for CSF1 and IL34 and plays an essential role in the regulation of survival, proliferation and differentiation of hematopoietic precursor c
- **SLC29A3** — Equilibrative nucleoside transporter 3 [Candidate gene tested in]
  - Função: Uniporter that mediates the facilitative transport of nucleoside across lysosomal and mitochondrial membranes (PubMed:15701636, PubMed:19164483, PubMed:20595384, PubMed:28729424). Functions as a non-e
- **SLC4A2** — Anion exchange protein 2 [Disease-causing germline mutation(s) in]
  - Função: Sodium-independent anion exchanger which mediates the electroneutral exchange of chloride for bicarbonate ions across the cell membrane (PubMed:15184086, PubMed:34668226). Plays an important role in o
- **LRP5** — Low-density lipoprotein receptor-related protein 5 [Disease-causing germline mutation(s) in]
  - Função: Acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signal by Wnt proteins (PubMed:11336703, PubMed:11448771, PubMed:11719191, PubMed:157785
- **CTSK** — Cathepsin K [Disease-causing germline mutation(s) in]
  - Função: Thiol protease involved in osteoclastic bone resorption and may participate partially in the disorder of bone remodeling. Displays potent endoprotease activity against fibrinogen at acid pH. May play
- **TNFRSF11A** — Tumor necrosis factor receptor superfamily member 11A [Disease-causing germline mutation(s) in]
  - Função: Receptor for TNFSF11/RANKL/TRANCE/OPGL; essential for RANKL-mediated osteoclastogenesis (PubMed:9878548). Its interaction with EEIG1 promotes osteoclastogenesis via facilitating the transcription of N
- **AMER1** — APC membrane recruitment protein 1 [Disease-causing germline mutation(s) in]
  - Função: Regulator of the canonical Wnt signaling pathway. Acts by specifically binding phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), translocating to the cell membrane and interacting with key regula
- **OSTM1** — Osteopetrosis-associated transmembrane protein 1 [Disease-causing germline mutation(s) in]
  - Função: Required for osteoclast and melanocyte maturation and function
- **CA2** — Carbonic anhydrase 2 [Disease-causing germline mutation(s) in]
  - Função: Catalyzes the reversible hydration of carbon dioxide (PubMed:11327835, PubMed:11802772, PubMed:11831900, PubMed:12056894, PubMed:12171926, PubMed:1336460, PubMed:14736236, PubMed:15300855, PubMed:1545
- **TNFSF11** — Tumor necrosis factor ligand superfamily member 11 [Disease-causing germline mutation(s) in]
  - Função: Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. Osteoclast differentiation and activation factor. Augments the ability of dendritic cells to stimulate naive T-cell proliferation. May be an
- **PLEKHM1** — Pleckstrin homology domain-containing family M member 1 [Disease-causing germline mutation(s) in]
  - Função: Acts as a multivalent adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways.
- **TCIRG1** — V-type proton ATPase 116 kDa subunit a 3 [Disease-causing germline mutation(s) in]
  - Função: Subunit of the V0 complex of vacuolar(H+)-ATPase (V-ATPase), a multisubunit enzyme composed of a peripheral complex (V1) that hydrolyzes ATP and a membrane integral complex (V0) that translocates prot

## Ensaios clínicos ativos (2)

- **NCT03333200** [RECRUITING]: Longitudinal Study of Neurodegenerative Disorders — https://clinicaltrials.gov/study/NCT03333200
- **NCT03301168** [ACTIVE_NOT_RECRUITING]: Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant — https://clinicaltrials.gov/study/NCT03301168
- **NCT01019876** [COMPLETED]: Risk-Adapted Allogeneic Stem Cell Transplantation For Mixed Donor Chimerism In Patients With Non-Malignant Diseases — https://clinicaltrials.gov/study/NCT01019876
- **NCT02666768** [COMPLETED]: ACTIMMUNE in Intermediate Osteopetrosis — https://clinicaltrials.gov/study/NCT02666768
- **NCT06521580** [COMPLETED]: Outcomes of Patients With Osteopetrosis Weight-bearing Bone Fractures — https://clinicaltrials.gov/study/NCT06521580
- **NCT02065869** [TERMINATED]: Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant — https://clinicaltrials.gov/study/NCT02065869
- **NCT00968864** [TERMINATED]: T-cell Depleted Alternative Donor Transplantation — https://clinicaltrials.gov/study/NCT00968864
- **NCT01200017** [NO_LONGER_AVAILABLE]: Expanded Access Protocol (EAP) Using the CliniMACS® Device for Pediatric Haplocompatible Donor Stem Cell Transplant — https://clinicaltrials.gov/study/NCT01200017
- **NCT00638820** [TERMINATED]: Reduced Intensity AlloTransplant For Osteopetrosis — https://clinicaltrials.gov/study/NCT00638820
- **NCT00145587** [TERMINATED]: Stem Cell Transplantation for Children Affected With Osteopetrosis — https://clinicaltrials.gov/study/NCT00145587

## Doenças relacionadas (por similaridade fenotípica)

- [Síndrome de osteopatia estriada-esclerose craniana](https://raras.org/doenca/sindrome-de-osteopatia-estriada-esclerose-craniana) — ORPHA:2780 — 99 sintomas em comum
- [Picnodisostose](https://raras.org/doenca/picnodisostose) — ORPHA:763 — 74 sintomas em comum
- [Osteopetrose com acidose tubular renal](https://raras.org/doenca/osteopetrose-com-acidose-tubular-renal) — ORPHA:2785 — 69 sintomas em comum
- [Síndrome Ehlers-Danlos espondilodisplásico B4GALT7-relacionado](https://raras.org/doenca/sindrome-ehlers-danlos-espondilodisplasico-b4galt7-relacionado) — ORPHA:75496 — 65 sintomas em comum
- [Síndrome de hipotonia-transtorno da linguagem-transtorno do desenvolvimento intelectual grave](https://raras.org/doenca/sindrome-de-hipotonia-transtorno-da-linguagem-transtorno-do-desenvolvimento-intelectual-grave) — ORPHA:371364 — 65 sintomas em comum
- [Osteopetrose com displasia neuroaxonal, forma da infância](https://raras.org/doenca/osteopetrose-com-displasia-neuroaxonal-forma-da-infancia) — ORPHA:85179 — 64 sintomas em comum
- [Monossomia parcial do braço curto do cromossomo 1](https://raras.org/doenca/monossomia-parcial-do-braco-curto-do-cromossomo-1) — ORPHA:261857 — 63 sintomas em comum
- [Condrodisplasia FGFR3-relacionada](https://raras.org/doenca/condrodisplasia-fgfr3-relacionada) — ORPHA:93420 — 63 sintomas em comum
- [Síndrome orelha-rótula-baixa estatura](https://raras.org/doenca/sindrome-orelha-rotula-baixa-estatura) — ORPHA:2554 — 62 sintomas em comum
- [Monossomia parcial do cromossomo 18](https://raras.org/doenca/monossomia-parcial-do-cromossomo-18) — ORPHA:261836 — 62 sintomas em comum

## Importante

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Pacientes devem consultar profissionais de saúde qualificados para decisões clínicas.

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