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Oculopharyngodistal myopathy 1(OPDM1)

MedGen UID:
1684682
Concept ID:
C5231388
Disease or Syndrome
Synonym: OPDM1
 
Gene (location): LRP12 (8q22.3)
 
Monarch Initiative: MONDO:0020793
OMIM®: 164310

Definition

Oculopharyngodistal myopathy-1 (OPDM1) is an autosomal dominant disorder characterized by adult-onset ptosis, external ophthalmoplegia, facial muscle weakness, distal limb muscle weakness and atrophy, and pharyngeal involvement, resulting in dysphagia and dysarthria. Skeletal muscle biopsy shows myopathic changes with rimmed vacuoles. There are variable manifestations of the disorder regarding muscle involvement and severity (summary by Ishiura et al., 2019). Genetic Heterogeneity of Oculopharyngodistal Myopathy See also OPDM2 (618940), caused by trinucleotide repeat expansion in the GIPC1 gene (605072) on chromosome 19p13; OPDM3 (619473), caused by trinucleotide repeat expansion in the NOTCH2NLC gene (618025) on chromosome 1q21; and OPDM4 (619790), caused by trinucleotide repeat expansion in the RILPL1 gene (614092) on chromosome 12q24. Oculopharyngeal muscular dystrophy (OPMD; 164300) is a similar disorder with overlapping features. It is caused by a similar heterozygous trinucleotide repeat expansion in the PABPN1 gene (602279) (summary by Durmus et al., 2011). [from OMIM]

Clinical features

From HPO
Foot dorsiflexor weakness
MedGen UID:
356163
Concept ID:
C1866141
Finding
Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.\n\nIt usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.
Hypertrophic cardiomyopathy
MedGen UID:
2881
Concept ID:
C0007194
Disease or Syndrome
Hypertrophic cardiomyopathy (HCM) is defined by the presence of increased ventricular wall thickness or mass in the absence of loading conditions (hypertension, valve disease) sufficient to cause the observed abnormality.
Paroxysmal atrial fibrillation
MedGen UID:
115990
Concept ID:
C0235480
Disease or Syndrome
Episodes of atrial fibrillation that typically last for several hours up to one day and terminate spontaneously.
Weight loss
MedGen UID:
853198
Concept ID:
C1262477
Finding
Reduction of total body weight.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dysarthria
MedGen UID:
8510
Concept ID:
C0013362
Mental or Behavioral Dysfunction
Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Abnormal cerebral white matter morphology
MedGen UID:
181756
Concept ID:
C0948163
Pathologic Function
An abnormality of the cerebral white matter.
Brain atrophy
MedGen UID:
1643639
Concept ID:
C4551584
Disease or Syndrome
Partial or complete wasting (loss) of brain tissue that was once present.
Muscle spasm
MedGen UID:
52431
Concept ID:
C0037763
Sign or Symptom
Sudden and involuntary contractions of one or more muscles.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Proximal muscle weakness
MedGen UID:
113169
Concept ID:
C0221629
Finding
A lack of strength of the proximal muscles.
Difficulty walking
MedGen UID:
86319
Concept ID:
C0311394
Finding
Reduced ability to walk (ambulate).
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.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
Autophagic vacuoles
MedGen UID:
107466
Concept ID:
C0544966
Finding
The lysosomal-vacuolar pathway has a role in the controlled intracellular digestion of macromolecules such as protein complexes and organelles. This feature refers to the presence of an abnormally increased number of autophagic vacuoles in muscle tissue.
Increased variability in muscle fiber diameter
MedGen UID:
336019
Concept ID:
C1843700
Finding
An abnormally high degree of muscle fiber size variation. This phenotypic feature can be observed upon muscle biopsy.
Distal amyotrophy
MedGen UID:
338530
Concept ID:
C1848736
Disease or Syndrome
Muscular atrophy affecting muscles in the distal portions of the extremities.
Rimmed vacuoles
MedGen UID:
340089
Concept ID:
C1853932
Finding
Presence of abnormal vacuoles (membrane-bound organelles) in the sarcolemma. On histological staining with hematoxylin and eosin, rimmed vacuoles are popcorn-like clear vacuoles with a densely blue rim. The vacuoles are often associated with cytoplasmic and occasionally intranuclear eosinophilic inclusions.
EMG: myopathic abnormalities
MedGen UID:
867362
Concept ID:
C4021726
Pathologic Function
The presence of abnormal electromyographic patterns indicative of myopathy, such as small-short polyphasic motor unit potentials.
EMG: myotonic discharges
MedGen UID:
867779
Concept ID:
C4022169
Finding
High frequency discharges in electromyography (EMG) that vary in amplitude and frequency, waxing and waning continuously with firing frequencies ranging from 150/second down to 20/second and producing a sound that has been referred to as a dive bomber sound.
Hypercapnia
MedGen UID:
9359
Concept ID:
C0020440
Sign or Symptom
Abnormally elevated blood carbon dioxide (CO2) level.
Bowing of the vocal cords
MedGen UID:
96005
Concept ID:
C0396064
Finding
Bowing (abnormal curvature) of the vocal folds.
Respiratory distress
MedGen UID:
96907
Concept ID:
C0476273
Sign or Symptom
Respiratory distress is objectively observable as the physical or emotional consequences from the experience of dyspnea. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.
Reduced forced vital capacity
MedGen UID:
337630
Concept ID:
C1846678
Finding
An abnormal reduction in the amount of air a person can expel following maximal inspiration.
Aspiration
MedGen UID:
751786
Concept ID:
C2712334
Finding
Inspiration of a foreign object into the airway.
Restrictive ventilatory defect
MedGen UID:
478856
Concept ID:
C3277226
Finding
A functional defect characterized by reduced total lung capacity (TLC) not associated with abnormalities of expiratory airflow or airway resistance. Spirometrically, a restrictive defect is defined as FEV1 (forced expiratory volume in 1 second) and FVC (forced vital capacity) less than 80 per cent. Restrictive lung disease may be caused by alterations in lung parenchyma or because of a disease of the pleura, chest wall, or neuromuscular apparatus.
Respiratory insufficiency due to muscle weakness
MedGen UID:
812797
Concept ID:
C3806467
Finding
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Hypernasal speech
MedGen UID:
107884
Concept ID:
C0566620
Finding
A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages.
Dysphonia
MedGen UID:
282893
Concept ID:
C1527344
Mental or Behavioral Dysfunction
Difficulty in speaking due to a physical disorder of the mouth, tongue, throat, or vocal cords. Associated with a known physical or neurological cause.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Myopathic facies
MedGen UID:
90695
Concept ID:
C0332615
Finding
A facial appearance characteristic of myopathic conditions. The face appears expressionless with sunken cheeks, bilateral ptosis, and inability to elevate the corners of the mouth, due to muscle weakness.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).
External ophthalmoplegia
MedGen UID:
57662
Concept ID:
C0162292
Disease or Syndrome
Paralysis of the external ocular muscles.
Ophthalmoparesis
MedGen UID:
155551
Concept ID:
C0751401
Sign or Symptom
Ophthalmoplegia is a paralysis or weakness of one or more of the muscles that control eye movement.
Bilateral ptosis
MedGen UID:
356120
Concept ID:
C1865916
Disease or Syndrome

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Fan Y, Xu Y, Shi C
J Med Genet 2022 Jan;59(1):1-9. Epub 2021 Oct 21 doi: 10.1136/jmedgenet-2021-107883. PMID: 34675123

Recent clinical studies

Etiology

Eura N, Noguchi S, Ogasawara M, Kumutpongpanich T, Hayashi S, Nishino I; OPDM/OPMD Image Study Group
J Neurol 2023 Dec;270(12):5988-5998. Epub 2023 Aug 27 doi: 10.1007/s00415-023-11906-9. PMID: 37634163
Shimizu T, Ishiura H, Hara M, Shibata S, Unuma A, Kubota A, Sakuishi K, Inoue K, Goto J, Takahashi Y, Shirota Y, Hamada M, Shimizu J, Tsuji S, Toda T
Muscle Nerve 2022 Dec;66(6):679-685. Epub 2022 Sep 27 doi: 10.1002/mus.27717. PMID: 36052448
Kumutpongpanich T, Ogasawara M, Ozaki A, Ishiura H, Tsuji S, Minami N, Hayashi S, Noguchi S, Iida A, Nishino I; OPDM_LRP12 Study Group, Mori-Yoshimura M, Oya Y, Ono K, Shimizu T, Kawata A, Shimohama S, Toyooka K, Endo K, Toru S, Sasaki O, Isahaya K, Takahashi MP, Iwasa K, Kira JI, Yamamoto T, Kawamoto M, Hamano T, Sugie K, Eura N, Shiota T, Koide M, Sekiya K, Kishi H, Hideyama T, Kawai S, Yanagimoto S, Sato H, Arahata H, Murayama S, Saito K, Hara H, Kanda T, Yaguchi H, Imai N, Kawagashira Y, Sanada M, Obara K, Kaido M, Furuta M, Kurashige T, Hara W, Kuzume D, Yamamoto M, Tsugawa J, Kishida H, Ishizuka N, Morimoto K, Tsuji Y, Tsuneyama A, Matsuno A, Sasaki R, Tamakoshi D, Abe E, Yamada S, Uzawa A
JAMA Neurol 2021 Jul 1;78(7):853-863. doi: 10.1001/jamaneurol.2021.1509. PMID: 34047774Free PMC Article

Diagnosis

Yang X, Zhang D, Shen S, Li P, Li M, Niu J, Ma D, Xu D, Li S, Guo X, Wang Z, Zhao Y, Ren H, Ling C, Wang Y, Fan Y, Shen J, Zhu Y, Wang D, Cui L, Chen L, Shi C, Dai Y
BMC Med Genomics 2023 Oct 20;16(1):253. doi: 10.1186/s12920-023-01586-9. PMID: 37864208Free PMC Article
Eura N, Noguchi S, Ogasawara M, Kumutpongpanich T, Hayashi S, Nishino I; OPDM/OPMD Image Study Group
J Neurol 2023 Dec;270(12):5988-5998. Epub 2023 Aug 27 doi: 10.1007/s00415-023-11906-9. PMID: 37634163
Ogasawara M, Eura N, Iida A, Kumutpongpanich T, Minami N, Nonaka I, Hayashi S, Noguchi S, Nishino I
Acta Neuropathol Commun 2022 Dec 7;10(1):176. doi: 10.1186/s40478-022-01482-w. PMID: 36476314Free PMC Article
Shimizu T, Ishiura H, Hara M, Shibata S, Unuma A, Kubota A, Sakuishi K, Inoue K, Goto J, Takahashi Y, Shirota Y, Hamada M, Shimizu J, Tsuji S, Toda T
Muscle Nerve 2022 Dec;66(6):679-685. Epub 2022 Sep 27 doi: 10.1002/mus.27717. PMID: 36052448
Kumutpongpanich T, Ogasawara M, Ozaki A, Ishiura H, Tsuji S, Minami N, Hayashi S, Noguchi S, Iida A, Nishino I; OPDM_LRP12 Study Group, Mori-Yoshimura M, Oya Y, Ono K, Shimizu T, Kawata A, Shimohama S, Toyooka K, Endo K, Toru S, Sasaki O, Isahaya K, Takahashi MP, Iwasa K, Kira JI, Yamamoto T, Kawamoto M, Hamano T, Sugie K, Eura N, Shiota T, Koide M, Sekiya K, Kishi H, Hideyama T, Kawai S, Yanagimoto S, Sato H, Arahata H, Murayama S, Saito K, Hara H, Kanda T, Yaguchi H, Imai N, Kawagashira Y, Sanada M, Obara K, Kaido M, Furuta M, Kurashige T, Hara W, Kuzume D, Yamamoto M, Tsugawa J, Kishida H, Ishizuka N, Morimoto K, Tsuji Y, Tsuneyama A, Matsuno A, Sasaki R, Tamakoshi D, Abe E, Yamada S, Uzawa A
JAMA Neurol 2021 Jul 1;78(7):853-863. doi: 10.1001/jamaneurol.2021.1509. PMID: 34047774Free PMC Article

Clinical prediction guides

Eura N, Noguchi S, Ogasawara M, Kumutpongpanich T, Hayashi S, Nishino I; OPDM/OPMD Image Study Group
J Neurol 2023 Dec;270(12):5988-5998. Epub 2023 Aug 27 doi: 10.1007/s00415-023-11906-9. PMID: 37634163
Kume K, Kurashige T, Muguruma K, Morino H, Tada Y, Kikumoto M, Miyamoto T, Akutsu SN, Matsuda Y, Matsuura S, Nakamori M, Nishiyama A, Izumi R, Niihori T, Ogasawara M, Eura N, Kato T, Yokomura M, Nakayama Y, Ito H, Nakamura M, Saito K, Riku Y, Iwasaki Y, Maruyama H, Aoki Y, Nishino I, Izumi Y, Aoki M, Kawakami H
Am J Hum Genet 2023 Jul 6;110(7):1086-1097. Epub 2023 Jun 19 doi: 10.1016/j.ajhg.2023.05.014. PMID: 37339631Free PMC Article
Shimizu T, Ishiura H, Hara M, Shibata S, Unuma A, Kubota A, Sakuishi K, Inoue K, Goto J, Takahashi Y, Shirota Y, Hamada M, Shimizu J, Tsuji S, Toda T
Muscle Nerve 2022 Dec;66(6):679-685. Epub 2022 Sep 27 doi: 10.1002/mus.27717. PMID: 36052448
Kumutpongpanich T, Ogasawara M, Ozaki A, Ishiura H, Tsuji S, Minami N, Hayashi S, Noguchi S, Iida A, Nishino I; OPDM_LRP12 Study Group, Mori-Yoshimura M, Oya Y, Ono K, Shimizu T, Kawata A, Shimohama S, Toyooka K, Endo K, Toru S, Sasaki O, Isahaya K, Takahashi MP, Iwasa K, Kira JI, Yamamoto T, Kawamoto M, Hamano T, Sugie K, Eura N, Shiota T, Koide M, Sekiya K, Kishi H, Hideyama T, Kawai S, Yanagimoto S, Sato H, Arahata H, Murayama S, Saito K, Hara H, Kanda T, Yaguchi H, Imai N, Kawagashira Y, Sanada M, Obara K, Kaido M, Furuta M, Kurashige T, Hara W, Kuzume D, Yamamoto M, Tsugawa J, Kishida H, Ishizuka N, Morimoto K, Tsuji Y, Tsuneyama A, Matsuno A, Sasaki R, Tamakoshi D, Abe E, Yamada S, Uzawa A
JAMA Neurol 2021 Jul 1;78(7):853-863. doi: 10.1001/jamaneurol.2021.1509. PMID: 34047774Free PMC Article
Xi J, Wang X, Yue D, Dou T, Wu Q, Lu J, Liu Y, Yu W, Qiao K, Lin J, Luo S, Li J, Du A, Dong J, Chen Y, Luo L, Yang J, Niu Z, Liang Z, Zhao C, Lu J, Zhu W, Zhou Y
Brain 2021 Mar 3;144(2):601-614. doi: 10.1093/brain/awaa426. PMID: 33374016

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