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Inclusion body myopathy with Paget disease of bone and frontotemporal dementia

MedGen UID:
322251
Concept ID:
C1833662
Disease or Syndrome
Synonyms: Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia; Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia
SNOMED CT: Lower motor neuron degeneration with Paget-like bone disease (703544004); Pagetoid amyotrophic lateral sclerosis (703544004); Muscular dystrophy limb-girdle with Paget disease of bone (703544004); Pagetoid neuroskeletal syndrome (703544004); Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia (703544004); IBMPFD - Inclusion body myopathy with early onset Paget disease and frontotemporal dementia (703544004)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Genes (locations): HNRNPA1 (12q13.13); HNRNPA2B1 (7p15.2); VCP (9p13.3)
 
Monarch Initiative: MONDO:0000507
OMIM®: 167320
OMIM® Phenotypic series: PS167320
Orphanet: ORPHA52430

Disease characteristics

Inclusion body myopathy associated with Paget disease of bone (PDB) and/or frontotemporal dementia (IBMPFD) is characterized by adult-onset proximal and distal muscle weakness (clinically resembling a limb-girdle muscular dystrophy syndrome), early-onset PDB, and premature frontotemporal dementia (FTD). Muscle weakness progresses to involve other limb and respiratory muscles. PDB involves focal areas of increased bone turnover that typically lead to spine and/or hip pain and localized enlargement and deformity of the long bones; pathologic fractures occur on occasion. Early stages of FTD are characterized by dysnomia, dyscalculia, comprehension deficits, and paraphasic errors, with minimal impairment of episodic memory; later stages are characterized by inability to speak, auditory comprehension deficits for even one-step commands, alexia, and agraphia. Mean age at diagnosis for muscle disease and PDB is 42 years; for FTD, 56 years. Dilated cardiomyopathy, amyotrophic lateral sclerosis, and Parkinson disease are now known to be part of the spectrum of findings associated with IBMPFD. [from GeneReviews]
Authors:
Virginia Kimonis   view full author information

Additional description

From MedlinePlus Genetics
Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia (IBMPFD) is a condition that can affect the muscles, bones, and brain.

The first symptom of IBMPFD is often muscle weakness (myopathy), which typically appears in mid-adulthood. Weakness first occurs in muscles of the hips and shoulders, making it difficult to climb stairs and raise the arms above the shoulders. As the disorder progresses, weakness develops in other muscles in the arms and legs.  Muscle weakness can also affect respiratory and heart (cardiac) muscles, leading to life-threatening breathing difficulties and heart failure.

About half of all adults with IBMPFD develop a disorder called Paget disease of bone. This disorder causes bones to grow larger and weaker than normal.Paget disease of bone most often affects bones of the hips, spine, and skull, and the long bones of the arms and legs. Bone pain, particularly in the hips and spine, is usually the major symptom of Paget disease. Other complications of Paget disease of bone depend on which bones are affected.Rarely, this condition can weaken bones so much that they break (fracture).

In about one-third of people with IBMPFD, the disorder also affects the brain. IBMPFD is associated with a brain condition called frontotemporal dementia, which becomes noticeable in a person's forties or fifties. People with frontotemporal dementia initially may have trouble speaking, remembering words and names (dysnomia), and using numbers (dyscalculia). Over time, the condition damages parts of the brain that control reasoning, personality, social skills, speech, and language. Personality changes, loss of judgment, and inappropriate social behavior are also hallmarks of the disease. As the dementia worsens, affected people ultimately become unable to speak, read, or care for themselves.

Additional features that rarely occur in IBMPFD include a severe and progressive muscular disease called amyotrophic lateral sclerosis and progressive problems with movement and balance(Parkinson's disease).

People with IBMPFD usually live into their fifties or sixties.  https://medlineplus.gov/genetics/condition/inclusion-body-myopathy-with-early-onset-paget-disease-and-frontotemporal-dementia

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVInclusion body myopathy with Paget disease of bone and frontotemporal dementia

Professional guidelines

PubMed

Mega A, Galluzzi S, Bonvicini C, Fostinelli S, Gennarelli M, Geroldi C, Zanetti O, Benussi L, Di Maria E, Frisoni GB
Alzheimers Res Ther 2020 Nov 17;12(1):152. doi: 10.1186/s13195-020-00720-4. PMID: 33203472Free PMC Article

Recent clinical studies

Etiology

Shmara A, Perez-Rosendahl M, Murphy K, Kwon A, Smith C, Kimonis V
Orphanet J Rare Dis 2022 Jul 15;17(1):272. doi: 10.1186/s13023-022-02403-9. PMID: 35841038Free PMC Article
Mega A, Galluzzi S, Bonvicini C, Fostinelli S, Gennarelli M, Geroldi C, Zanetti O, Benussi L, Di Maria E, Frisoni GB
Alzheimers Res Ther 2020 Nov 17;12(1):152. doi: 10.1186/s13195-020-00720-4. PMID: 33203472Free PMC Article
Shamirian S, Nalbandian A, Khare M, Castellani R, Kim R, Kimonis VE
Alzheimer Dis Assoc Disord 2015 Jan-Mar;29(1):90-3. doi: 10.1097/WAD.0b013e318298e54f. PMID: 23715207

Diagnosis

Mega A, Galluzzi S, Bonvicini C, Fostinelli S, Gennarelli M, Geroldi C, Zanetti O, Benussi L, Di Maria E, Frisoni GB
Alzheimers Res Ther 2020 Nov 17;12(1):152. doi: 10.1186/s13195-020-00720-4. PMID: 33203472Free PMC Article
Shamirian S, Nalbandian A, Khare M, Castellani R, Kim R, Kimonis VE
Alzheimer Dis Assoc Disord 2015 Jan-Mar;29(1):90-3. doi: 10.1097/WAD.0b013e318298e54f. PMID: 23715207

Therapy

Wang HF, Shih YT, Chen CY, Chao HW, Lee MJ, Hsueh YP
J Clin Invest 2011 Dec;121(12):4820-37. Epub 2011 Nov 21 doi: 10.1172/JCI45677. PMID: 22105171Free PMC Article

Prognosis

Mega A, Galluzzi S, Bonvicini C, Fostinelli S, Gennarelli M, Geroldi C, Zanetti O, Benussi L, Di Maria E, Frisoni GB
Alzheimers Res Ther 2020 Nov 17;12(1):152. doi: 10.1186/s13195-020-00720-4. PMID: 33203472Free PMC Article
Shamirian S, Nalbandian A, Khare M, Castellani R, Kim R, Kimonis VE
Alzheimer Dis Assoc Disord 2015 Jan-Mar;29(1):90-3. doi: 10.1097/WAD.0b013e318298e54f. PMID: 23715207

Clinical prediction guides

Mega A, Galluzzi S, Bonvicini C, Fostinelli S, Gennarelli M, Geroldi C, Zanetti O, Benussi L, Di Maria E, Frisoni GB
Alzheimers Res Ther 2020 Nov 17;12(1):152. doi: 10.1186/s13195-020-00720-4. PMID: 33203472Free PMC Article

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