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Osteosclerotic metaphyseal dysplasia(OSMD)

MedGen UID:
767579
Concept ID:
C3554665
Disease or Syndrome
Synonym: OSMD
SNOMED CT: Osteosclerotic metaphyseal dysplasia (1237513008)
 
Gene (location): LRRK1 (15q26.3)
 
Monarch Initiative: MONDO:0014080
OMIM®: 615198
Orphanet: ORPHA500548

Definition

Osteosclerotic metaphyseal dysplasia (OSMD) is a rare condition characterized by distinctive radiographic changes, including osteosclerosis localized predominantly to the metaphyses of the long bones. The shafts of the long bones are osteopenic. Laboratory abnormalities include elevated alkaline phosphatase levels in some, but not all, patients. Elevated urinary pyridinoline and deoxypyridinoline levels, markers of osteoclastic activity, have also been reported (Nishimura and Kozlowski, 1993; Kasapkara et al., 2013; Guo et al., 2017). Patients with OSMD have been described who also show hypotonia, developmental delay, seizures, and later-onset spastic paraplegia; however, OSMD resulting from mutation in the LRRK1 gene does not appear to include these neurologic features (Nishimura and Kozlowski, 1993; Kasapkara et al., 2013; Guo et al., 2017). Reviews Howaldt et al. (2020) reviewed published reports of LRRK1-associated OSMD, and noted that patients typically present with recurrent pathologic fractures and osteosclerosis at multiple skeletal sites, predominantly at the metaphyses and vertebral bodies. Variable degrees of osteosclerosis of ribs and skull and of Erlenmeyer flask deformity of the femurs have been observed. [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.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Increased bone mineral density
MedGen UID:
10502
Concept ID:
C0029464
Disease or Syndrome
An abnormal increase of bone mineral density, that is, of the amount of matter per cubic centimeter of bones which is often referred to as osteosclerosis. Osteosclerosis can be detected on radiological examination as an increased whiteness (density) of affected bones.
Clavicular sclerosis
MedGen UID:
767583
Concept ID:
C3554669
Finding
An increase in bone density within the clavicle.
Dense metaphyseal bands
MedGen UID:
866573
Concept ID:
C4020919
Finding
Dense radiopaque bands of bone which are thicker than the adjacent diaphyseal cortex and may form at the metaphysis of growing bones. They appear on radiographs as bone that is more radiopaque that the adjacent diaphyseal cortex.
Sclerotic vertebral endplates
MedGen UID:
1642576
Concept ID:
C4551970
Finding
Sclerosis (increased density) affecting vertebral end plates.
Metaphyseal dysplasia
MedGen UID:
1677924
Concept ID:
C5194606
Disease or Syndrome
The presence of dysplastic regions in metaphyseal regions.
Elevated circulating alkaline phosphatase concentration
MedGen UID:
727252
Concept ID:
C1314665
Finding
Abnormally increased serum levels of alkaline phosphatase activity.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVOsteosclerotic metaphyseal dysplasia

Recent clinical studies

Etiology

Magalhães BM, Catarino L, Carreiro I, Gomes RAMP, Gaspar RR, Matos VMJ, Santos AL
Int J Paleopathol 2021 Sep;34:134-141. Epub 2021 Jul 6 doi: 10.1016/j.ijpp.2021.06.002. PMID: 34243133
Howaldt A, Hennig AF, Rolvien T, Rössler U, Stelzer N, Knaus A, Böttger S, Zustin J, Geißler S, Oheim R, Amling M, Howaldt HP, Kornak U
J Bone Miner Res 2020 Jul;35(7):1322-1332. Epub 2020 Mar 19 doi: 10.1002/jbmr.3995. PMID: 32119750
Miryounesi M, Nikfar A, Changi-Ashtiani M, Shahrooei M, Dinmohammadi H, Shahani T, Zarvandi S, Bahrami T, Momenilandi M, Rokni-Zadeh H
Ann Hum Genet 2020 Jan;84(1):102-106. Epub 2019 Sep 30 doi: 10.1111/ahg.12352. PMID: 31571209
Nishimura G, Kozlowski K
Pediatr Radiol 1993;23(6):450-2. doi: 10.1007/BF02012448. PMID: 8255649

Diagnosis

Pieridou C, Sabir A, Lancashire J, Liang Y, McMillan K, Shaw N, Uday S
Front Endocrinol (Lausanne) 2023;14:1258340. Epub 2023 Oct 18 doi: 10.3389/fendo.2023.1258340. PMID: 37920250Free PMC Article
Chundoo S, McGoldrick DM, Williams R, McMillan K
BMJ Case Rep 2022 May 12;15(5) doi: 10.1136/bcr-2021-246789. PMID: 35550322Free PMC Article
Guo L, Girisha KM, Iida A, Hebbar M, Shukla A, Shah H, Nishimura G, Matsumoto N, Nismath S, Miyake N, Ikegawa S
J Hum Genet 2017 Mar;62(3):437-441. Epub 2016 Nov 10 doi: 10.1038/jhg.2016.136. PMID: 27829680
Zheng H, Cai J, Wang L, He X
Skeletal Radiol 2015 Oct;44(10):1529-33. Epub 2015 Jun 18 doi: 10.1007/s00256-015-2190-9. PMID: 26084987
Kasapkara CS, Küçükçongar A, Boyunağa O, Bedir T, Oncü F, Hasanoğlu A, Tümer L
Genet Couns 2013;24(1):69-74. PMID: 23610867

Prognosis

Pieridou C, Sabir A, Lancashire J, Liang Y, McMillan K, Shaw N, Uday S
Front Endocrinol (Lausanne) 2023;14:1258340. Epub 2023 Oct 18 doi: 10.3389/fendo.2023.1258340. PMID: 37920250Free PMC Article
Turan S
Bone 2023 Feb;167:116615. Epub 2022 Nov 17 doi: 10.1016/j.bone.2022.116615. PMID: 36402365
Miryounesi M, Nikfar A, Changi-Ashtiani M, Shahrooei M, Dinmohammadi H, Shahani T, Zarvandi S, Bahrami T, Momenilandi M, Rokni-Zadeh H
Ann Hum Genet 2020 Jan;84(1):102-106. Epub 2019 Sep 30 doi: 10.1111/ahg.12352. PMID: 31571209
Iida A, Xing W, Docx MK, Nakashima T, Wang Z, Kimizuka M, Van Hul W, Rating D, Spranger J, Ohashi H, Miyake N, Matsumoto N, Mohan S, Nishimura G, Mortier G, Ikegawa S
J Med Genet 2016 Aug;53(8):568-74. Epub 2016 Apr 7 doi: 10.1136/jmedgenet-2016-103756. PMID: 27055475Free PMC Article
Nishimura G, Kozlowski K
Pediatr Radiol 1993;23(6):450-2. doi: 10.1007/BF02012448. PMID: 8255649

Clinical prediction guides

Pieridou C, Sabir A, Lancashire J, Liang Y, McMillan K, Shaw N, Uday S
Front Endocrinol (Lausanne) 2023;14:1258340. Epub 2023 Oct 18 doi: 10.3389/fendo.2023.1258340. PMID: 37920250Free PMC Article
Turan S
Bone 2023 Feb;167:116615. Epub 2022 Nov 17 doi: 10.1016/j.bone.2022.116615. PMID: 36402365
Iida A, Xing W, Docx MK, Nakashima T, Wang Z, Kimizuka M, Van Hul W, Rating D, Spranger J, Ohashi H, Miyake N, Matsumoto N, Mohan S, Nishimura G, Mortier G, Ikegawa S
J Med Genet 2016 Aug;53(8):568-74. Epub 2016 Apr 7 doi: 10.1136/jmedgenet-2016-103756. PMID: 27055475Free PMC Article
Zheng H, Cai J, Wang L, He X
Skeletal Radiol 2015 Oct;44(10):1529-33. Epub 2015 Jun 18 doi: 10.1007/s00256-015-2190-9. PMID: 26084987

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