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Autosomal recessive osteopetrosis 8(OPTB8)

MedGen UID:
767392
Concept ID:
C3554478
Disease or Syndrome
Synonyms: OPTB8; OSTEOPETROSIS, AUTOSOMAL RECESSIVE 8
 
Gene (location): SNX10 (7p15.2)
 
Monarch Initiative: MONDO:0014040
OMIM®: 615085

Definition

Autosomal recessive osteopetrosis-8 (OPTB8) is characterized by the 'classical' features of osteopetrosis, macrocephaly, hepatosplenomegaly, and visual impairment, with varying severity (summary by Megarbane et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive osteopetrosis, see OPTB1 (259700). [from OMIM]

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A reduction in the number of circulating thrombocytes.
Osteopetrosis
MedGen UID:
18223
Concept ID:
C0029454
Finding
Abnormally increased formation of dense trabecular bone tissue. Despite the increased density of bone tissue, osteopetrotic bones tend to be more fracture-prone than normal.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Facial palsy
MedGen UID:
87660
Concept ID:
C0376175
Disease or Syndrome
Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Splenomegaly
MedGen UID:
52469
Concept ID:
C0038002
Finding
Abnormal increased size of the spleen.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Unilateral microphthalmos
MedGen UID:
768664
Concept ID:
C3640024
Disease or Syndrome
A developmental anomaly characterized by abnormal smallness of one eye.
Visual loss
MedGen UID:
784038
Concept ID:
C3665386
Finding
Loss of visual acuity (implying that vision was better at a certain time point in life). Otherwise the term reduced visual acuity should be used (or a subclass of that).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVAutosomal recessive osteopetrosis 8

Professional guidelines

PubMed

Even-Or E, Schiesel G, Simanovsky N, NaserEddin A, Zaidman I, Elpeleg O, Mor-Shaked H, Stepensky P
Bone 2022 Jan;154:116229. Epub 2021 Oct 8 doi: 10.1016/j.bone.2021.116229. PMID: 34624559

Recent clinical studies

Etiology

Shamsian BS, Momtazmanesh N, Saneifard H, Tabatabaei SMTH, Jafari M, Pour ZK, Al-Hussieni KJMR, Jamee M, Kamfar S
Pediatr Transplant 2024 May;28(3):e14689. doi: 10.1111/petr.14689. PMID: 38655726
Even-Or E, Schiesel G, Simanovsky N, NaserEddin A, Zaidman I, Elpeleg O, Mor-Shaked H, Stepensky P
Bone 2022 Jan;154:116229. Epub 2021 Oct 8 doi: 10.1016/j.bone.2021.116229. PMID: 34624559
Shadur B, Zaidman I, NaserEddin A, Lokshin E, Hussein F, Oron HC, Avni B, Grisariu S, Stepensky P
Pediatr Blood Cancer 2018 Jun;65(6):e27010. Epub 2018 Feb 22 doi: 10.1002/pbc.27010. PMID: 29469225
Carn G, Koller DL, Peacock M, Hui SL, Evans WE, Conneally PM, Johnston CC Jr, Foroud T, Econs MJ
J Clin Endocrinol Metab 2002 Aug;87(8):3819-24. doi: 10.1210/jcem.87.8.8740. PMID: 12161516
Bénichou O, Cleiren E, Gram J, Bollerslev J, de Vernejoul MC, Van Hul W
Am J Hum Genet 2001 Sep;69(3):647-54. Epub 2001 Jul 23 doi: 10.1086/323132. PMID: 11468688Free PMC Article

Diagnosis

Even-Or E, Schiesel G, Simanovsky N, NaserEddin A, Zaidman I, Elpeleg O, Mor-Shaked H, Stepensky P
Bone 2022 Jan;154:116229. Epub 2021 Oct 8 doi: 10.1016/j.bone.2021.116229. PMID: 34624559
Liang H, Li N, Yao RE, Yu T, Ding L, Chen J, Wang J
Mol Genet Genomic Med 2021 Nov;9(11):e1815. Epub 2021 Sep 21 doi: 10.1002/mgg3.1815. PMID: 34545712Free PMC Article
Chávez-Güitrón LE, Cerón-Torres T, Sobacchi C, Ochoa-Ruiz E, Villegas-Huesca S
Bol Med Hosp Infant Mex 2018;75(4):255-259. doi: 10.24875/BMHIM.M18000028. PMID: 30084437
Phadke SR, Fischer B, Gupta N, Ranganath P, Kabra M, Kornak U
Indian J Med Res 2010 Apr;131:508-14. PMID: 20424301
Elster AD, Theros EG, Key LL, Chen MY
Radiology 1992 Apr;183(1):137-44. doi: 10.1148/radiology.183.1.1549660. PMID: 1549660

Therapy

Shadur B, Zaidman I, NaserEddin A, Lokshin E, Hussein F, Oron HC, Avni B, Grisariu S, Stepensky P
Pediatr Blood Cancer 2018 Jun;65(6):e27010. Epub 2018 Feb 22 doi: 10.1002/pbc.27010. PMID: 29469225
Moscatelli I, Löfvall H, Schneider Thudium C, Rothe M, Montano C, Kertész Z, Sirin M, Schulz A, Schambach A, Henriksen K, Richter J
Hum Gene Ther 2018 Aug;29(8):938-949. Epub 2017 Oct 3 doi: 10.1089/hum.2017.053. PMID: 28726516
Krupin T, Sly WS, Whyte MP, Dodgson SJ
Am J Ophthalmol 1985 Apr 15;99(4):396-9. doi: 10.1016/0002-9394(85)90004-2. PMID: 3920916

Prognosis

Dulski J, Souza J, Santos ML, Wszolek ZK
Orphanet J Rare Dis 2023 Jun 22;18(1):160. doi: 10.1186/s13023-023-02772-9. PMID: 37349768Free PMC Article
Zirngibl RA, Wang A, Yao Y, Manolson MF, Krueger J, Dupuis L, Mendoza-Londono R, Voronov I
J Cell Biochem 2019 Oct;120(10):17180-17193. Epub 2019 May 20 doi: 10.1002/jcb.28979. PMID: 31111556
Shadur B, Zaidman I, NaserEddin A, Lokshin E, Hussein F, Oron HC, Avni B, Grisariu S, Stepensky P
Pediatr Blood Cancer 2018 Jun;65(6):e27010. Epub 2018 Feb 22 doi: 10.1002/pbc.27010. PMID: 29469225
Zhang X, Wei Z, He J, Wang C, Zhang Z
Postgrad Med 2017 Nov;129(8):934-942. Epub 2017 Oct 11 doi: 10.1080/00325481.2017.1386529. PMID: 28975865
Phadke SR, Fischer B, Gupta N, Ranganath P, Kabra M, Kornak U
Indian J Med Res 2010 Apr;131:508-14. PMID: 20424301

Clinical prediction guides

Dulski J, Souza J, Santos ML, Wszolek ZK
Orphanet J Rare Dis 2023 Jun 22;18(1):160. doi: 10.1186/s13023-023-02772-9. PMID: 37349768Free PMC Article
Zirngibl RA, Wang A, Yao Y, Manolson MF, Krueger J, Dupuis L, Mendoza-Londono R, Voronov I
J Cell Biochem 2019 Oct;120(10):17180-17193. Epub 2019 May 20 doi: 10.1002/jcb.28979. PMID: 31111556
Zhang Y, Ji D, Li L, Yang S, Zhang H, Duan X
Theranostics 2019;9(5):1387-1400. Epub 2019 Feb 20 doi: 10.7150/thno.29761. PMID: 30867839Free PMC Article
Menale C, Campodoni E, Palagano E, Mantero S, Erreni M, Inforzato A, Fontana E, Schena F, Van't Hof R, Sandri M, Tampieri A, Villa A, Sobacchi C
Stem Cells Transl Med 2019 Jan;8(1):22-34. Epub 2018 Sep 5 doi: 10.1002/sctm.18-0085. PMID: 30184340Free PMC Article
Elster AD, Theros EG, Key LL, Chen MY
Radiology 1992 Apr;183(1):137-44. doi: 10.1148/radiology.183.1.1549660. PMID: 1549660

Recent systematic reviews

Dulski J, Souza J, Santos ML, Wszolek ZK
Orphanet J Rare Dis 2023 Jun 22;18(1):160. doi: 10.1186/s13023-023-02772-9. PMID: 37349768Free PMC Article

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