Online Mendelian Inheritance in Man (OMIM) (2023)

NUMBER	# 117000	# 145600	# 255320	# 619542
TITLE	CONGENITAL MYOPATHY 1A, AUTOSOMAL DOMINANT, WITH SUSCEPTIBILITY TO MALIGNANT HYPERTHERMIA; CMYP1A	MALIGNANT HYPERTHERMIA, SUSCEPTIBILITY TO, 1; MHS1	CONGENITAL MYOPATHY 1B, AUTOSOMAL RECESSIVE; CMYP1B	KING-DENBOROUGH SYNDROME; KDS
GENE	RYR1 - 180901	RYR1 - 180901	RYR1 - 180901	RYR1 - 180901
INHERITANCE (in 4/4)	- Autosomal dominant [SNOMEDCT: 771269000, 263681008] [UMLS: C1867440, C0443147 HPO: HP:0000006] [HPO: HP:0000006]	- Autosomal dominant [SNOMEDCT: 771269000, 263681008] [UMLS: C1867440, C0443147 HPO: HP:0000006] [HPO: HP:0000006]	- Autosomal recessive [SNOMEDCT: 258211005] [UMLS: C0441748 HPO: HP:0000007] [HPO: HP:0000007]	- Autosomal dominant [SNOMEDCT: 771269000, 263681008] [UMLS: C1867440, C0443147 HPO: HP:0000006] [HPO: HP:0000006]
GROWTH (in 1/4)
				Height - Short stature (in some patients) [SNOMEDCT: 237837007, 237836003, 422065006] [ICD10CM: R62.52, E34.31] [ICD9CM: 783.43] [UMLS: C0349588, C0013336 HPO: HP:0003510, HP:0004322] [HPO: HP:0004322]


HEAD & NECK (in 3/4)

	Face - Facial muscle weakness [SNOMEDCT: 95666008] [ICD10CM: R29.810] [ICD9CM: 781.94, 438.83] [UMLS: C0427055 HPO: HP:0030319, HP:0007209] [HPO: HP:0030319]		Face - Facial weakness [SNOMEDCT: 95666008] [ICD10CM: R29.810] [ICD9CM: 781.94, 438.83] [UMLS: C0427055 HPO: HP:0030319, HP:0007209] [HPO: HP:0030319] - Myopathic facies [SNOMEDCT: 26432009] [UMLS: C0332615 HPO: HP:0002058] [HPO: HP:0002058]	Face - Myopathic facies [SNOMEDCT: 26432009] [UMLS: C0332615 HPO: HP:0002058] [HPO: HP:0002058]
				Ears - Low-set ears [SNOMEDCT: 95515009] [ICD10CM: Q17.4] [UMLS: C0239234 HPO: HP:0000369] [HPO: HP:0000369]
			Eyes - External ophthalmoplegia affecting upward and lateral gaze [UMLS: C1850675] - Ptosis [SNOMEDCT: 29696001, 11934000] [ICD10CM: H02.409, H02.40, H02.4] [ICD9CM: 374.30, 374.3] [UMLS: C0005745, C0033377 HPO: HP:0000508] [HPO: HP:0000508]	Eyes - Ptosis [SNOMEDCT: 29696001, 11934000] [ICD10CM: H02.409, H02.40, H02.4] [ICD9CM: 374.30, 374.3] [UMLS: C0005745, C0033377 HPO: HP:0000508] [HPO: HP:0000508] - Hypertelorism [SNOMEDCT: 22006008] [ICD10CM: Q75.2] [ICD9CM: 376.41] [UMLS: C0020534 HPO: HP:0000316] [HPO: HP:0000316] - Down-slanting palpebral fissures [SNOMEDCT: 246800008] [UMLS: C0423110 HPO: HP:0000494] [HPO: HP:0000494]

	Mouth - High arched palate [SNOMEDCT: 27272007] [ICD10CM: Q38.5] [UMLS: C0240635 HPO: HP:0000218] [HPO: HP:0000218]		Mouth - High-arched palate [SNOMEDCT: 27272007] [ICD10CM: Q38.5] [UMLS: C0240635 HPO: HP:0000218] [HPO: HP:0000218] - Inverted V-shaped mouth [UMLS: C1845453]

	Neck - Neck muscle weakness [UMLS: C0240479 HPO: HP:0000467] [HPO: HP:0000467]			Neck - Webbed neck [SNOMEDCT: 11731003] [ICD10CM: Q18.3] [ICD9CM: 744.5] [UMLS: C0221217 HPO: HP:0000465] [HPO: HP:0000465]
CARDIOVASCULAR (in 1/4)
		Heart - Tachycardia [SNOMEDCT: 3424008, 86651002] [ICD10CM: R00.0] [ICD9CM: 785.0] [UMLS: C3827868, C0039231 HPO: HP:0001649] [HPO: HP:0001649] - Cardiac arrhythmias [SNOMEDCT: 698247007] [ICD10CM: I49.9] [ICD9CM: 427, 427.9] [UMLS: C0003811 HPO: HP:0011675] [HPO: HP:0011675]
		Vascular - Hypotension [SNOMEDCT: 45007003] [ICD10CM: I95.9, I95] [ICD9CM: 458, 458.9] [UMLS: C0020649 HPO: HP:0002615] [HPO: HP:0002615]
RESPIRATORY (in 2/4)	- Reduced functional vital capacity (in some patients) - Respiratory insufficiency [SNOMEDCT: 409623005, 409622000] [ICD10CM: J96.9] [UMLS: C1145670, C0035229 HPO: HP:0002093, HP:0002878] [HPO: HP:0002093]		- Frequent respiratory infections [UMLS: C3806482 HPO: HP:0002205] [HPO: HP:0002205] - Respiratory insufficiency [SNOMEDCT: 409623005, 409622000] [ICD10CM: J96.9] [UMLS: C1145670, C0035229 HPO: HP:0002093, HP:0002878] [HPO: HP:0002093] - Respiratory impairment [SNOMEDCT: 409623005] [UMLS: C0035229 HPO: HP:0002093] [HPO: HP:0002093] - Lung hypoplasia [SNOMEDCT: 80825009] [UMLS: C0265783 HPO: HP:0002089] [HPO: HP:0002089]




ABDOMEN (in 1/4)





			Gastrointestinal - Feeding difficulties [SNOMEDCT: 78164000] [ICD10CM: R63.3] [UMLS: C0232466 HPO: HP:0011968] [HPO: HP:0011968]
SKELETAL (in 3/4)	- Joint contractures [SNOMEDCT: 7890003] [ICD10CM: M24.5] [ICD9CM: 718.40, 718.4] [UMLS: C0009918 HPO: HP:0034392]		- Ligamentous laxity [SNOMEDCT: 27911000, 298203008] [ICD10CM: M24.2] [ICD9CM: 728.4] [UMLS: C0158359, C0086437 HPO: HP:0001388] [HPO: HP:0001388] - Contractures [SNOMEDCT: 55033002, 57048009] [ICD10CM: M62.4, M62.40] [UMLS: C0009917]	- Joint laxity [SNOMEDCT: 298203008] [UMLS: C0086437 HPO: HP:0001388] [HPO: HP:0001388]

	Spine - Scoliosis [SNOMEDCT: 20944008, 298382003, 111266001] [ICD10CM: Q67.5, M41, M41.9] [UMLS: C0559260, C0036439, C0700208 HPO: HP:0002650] [HPO: HP:0002650] - Lordosis [SNOMEDCT: 249710008, 1187290008, 61960001] [ICD10CM: M40.5] [UMLS: C0599412, C0024003 HPO: HP:0003307] [HPO: HP:0003307]		Spine - Scoliosis [SNOMEDCT: 20944008, 298382003, 111266001] [ICD10CM: Q67.5, M41, M41.9] [UMLS: C0559260, C0036439, C0700208 HPO: HP:0002650] [HPO: HP:0002650]	Spine - Kyphoscoliosis [SNOMEDCT: 405773007, 405772002, 405771009] [ICD10CM: M41] [UMLS: C0575158, C0345392, C0600033 HPO: HP:0002751, HP:0008453] [HPO: HP:0002751] - Lumbar lordosis [SNOMEDCT: 313471000119104] [UMLS: C1184923 HPO: HP:0002938] [HPO: HP:0002938]
	Pelvis - Congenital hip dislocation [SNOMEDCT: 48334007, 52781008] [ICD10CM: Q65.2] [ICD9CM: 754.3] [UMLS: C4551649, C0019555 HPO: HP:0001374, HP:0001385] [HPO: HP:0001374]		Pelvis - Hip dislocation [SNOMEDCT: 157265008] [ICD10CM: S73.00] [ICD9CM: 835] [UMLS: C0019554 HPO: HP:0002827] [HPO: HP:0002827]
	Limbs - Achilles tendon contractures [SNOMEDCT: 203076007] [UMLS: C0410264 HPO: HP:0001771] [HPO: HP:0001771]			Limbs - Patellar dislocation, recurrent [SNOMEDCT: 202246002] [ICD10CM: M22.00, M22.0] [UMLS: C0409412 HPO: HP:0005001] [HPO: HP:0002999]

	Feet - Foot deformities [SNOMEDCT: 229844004] [UMLS: C0016506 HPO: HP:0001760] [HPO: HP:0001760] - Flat feet [SNOMEDCT: 203534009, 53226007] [ICD10CM: M21.4] [ICD9CM: 734] [UMLS: C0264133, C0016202 HPO: HP:0001763] [HPO: HP:0001763]
MUSCLE, SOFT TISSUES (in 4/4)	- Muscle weakness, diffuse [ICD10CM: M62.81] [ICD9CM: 728.87] [UMLS: C0746674 HPO: HP:0003324] [HPO: HP:0003324] - Neonatal hypotonia [SNOMEDCT: 33010005, 240080003, 205294008] [ICD10CM: P94.2] [UMLS: C0343239, C0270971, C2267233 HPO: HP:0001319] [HPO: HP:0001319] - Proximal muscle weakness (lower limbs more affected than upper limbs) [SNOMEDCT: 249939004] [UMLS: C0221629 HPO: HP:0003701] [HPO: HP:0003701] - Positive Gowers sign [SNOMEDCT: 298294005] [UMLS: C0575071 HPO: HP:0003391] [HPO: HP:0003391] - Muscle atrophy [SNOMEDCT: 88092000] [UMLS: C0026846, C0541794 HPO: HP:0003202] [HPO: HP:0003202] - Type 1 muscle fibers with clearly demarcated central 'core' regions of sarcomeric disorganization, lack of oxidative activity, and absent mitochondria [UMLS: C1861754] - Type 1 muscle fiber predominance [UMLS: C1854387 HPO: HP:0003803] [HPO: HP:0003803] - Uniformity of type 1 fibers - Cores contain densely packed myofilaments [UMLS: C1861755] - Cores have abrupt borders within normal regions of the muscle fiber [UMLS: C2675851] - Cores extend along length of muscle fiber [UMLS: C1970102] - Changes in sarcoplasmic reticulum and t-tubules [UMLS: C1861757] - Increased internal nuclei in skeletal muscle fibers [UMLS: C1861758] - Nemaline rods (in some patients) [UMLS: C3808039 HPO: HP:0003798] [HPO: HP:0003798] - Relative sparing of the rectus femoris [UMLS: C4012153]	- Muscle rigidity [SNOMEDCT: 16046003] [UMLS: C0026837 HPO: HP:0002063] [HPO: HP:0002063] - Rhabdomyolysis [SNOMEDCT: 240131006, 89010004] [ICD10CM: M62.82] [ICD9CM: 728.88] [UMLS: C0035410 HPO: HP:0003201] [HPO: HP:0003201]	- Hypotonia, neonatal [SNOMEDCT: 205294008] [UMLS: C2267233 HPO: HP:0001319] [HPO: HP:0001319] - Proximal muscle weakness [SNOMEDCT: 249939004] [UMLS: C0221629 HPO: HP:0003701] [HPO: HP:0003701] - Axial muscle weakness [UMLS: C1843697 HPO: HP:0003327] [HPO: HP:0003327] - Muscle weakness, diffuse [ICD10CM: M62.81] [ICD9CM: 728.87] [UMLS: C0746674 HPO: HP:0003324] [HPO: HP:0003324] - Muscle atrophy, limb-girdle and proximal [UMLS: C1850679] - Exercise-induced myalgia [UMLS: C1850830 HPO: HP:0003738] [HPO: HP:0003738] - Difficulty running or inability to run [UMLS: C1850681] - Walking may be limited [UMLS: C1850682] - Myopathic changes, nonspecific, seen on muscle biopsy [UMLS: C4228976] [SNOMEDCT: 129565002] [ICD10CM: M62.9, G72.9, M60-M63] [ICD9CM: 359.9] [HPO: HP:0003198] - Merosin-positive biopsy [UMLS: C1843699] - Focal loss of cross striations seen on muscle biopsy [UMLS: C4231066] - Disorganization of the myofibrillar pattern [UMLS: C1850686] - Variation in muscle fiber size [UMLS: C1843700 HPO: HP:0003557] [HPO: HP:0003557] - Increased central nucleation [UMLS: C1850687] - Increased connective tissue [UMLS: C1866021 HPO: HP:0009025] [HPO: HP:0009025] - Type 1 fiber atrophy [UMLS: C1850688] - Type 1 fiber predominance [UMLS: C2673678] - Type 2 fiber hypertrophy [UMLS: C3278547] - Fiber type disproportion [SNOMEDCT: 240084007] [UMLS: C0546264] - Type 1 and type 2 muscle fibers with 'minicore' regions of sarcomeric disorganization, lack of oxidative activity, and absent mitochondria [UMLS: C1843701] - Minicores extend full fiber diameter [UMLS: C1850689] - Minicore regions are poorly defined and do not extend through entire fiber length [UMLS: C1843702] - Dystrophic changes may be present [UMLS: C1843703] - Z-line streaming seen on electron microscopy [UMLS: C4478279] - Nemaline rods (rare) [UMLS: C3808039 HPO: HP:0003798] [HPO: HP:0003798] - Greater sartorius involvement than gracilis involvement seen on MRI [UMLS: C3806470] - Greater soleus involvement than gastrocnemii involvement seen on MRI [UMLS: C3806471] - Relative sparing of the rectus femoris [UMLS: C4012153] - Relative sparing of the tibialis anterior [UMLS: C4012154]	- Hypotonia [SNOMEDCT: 398152000, 398151007] [UMLS: C0026827, C1858120 HPO: HP:0001252, HP:0001290] [HPO: HP:0001252] - Proximal muscle weakness [SNOMEDCT: 249939004] [UMLS: C0221629 HPO: HP:0003701] [HPO: HP:0003701] - Muscle atrophy [SNOMEDCT: 88092000] [UMLS: C0026846, C0541794 HPO: HP:0003202] [HPO: HP:0003202] - Variation in muscle fiber size [UMLS: C1843700 HPO: HP:0003557] [HPO: HP:0003557]
NEUROLOGIC (in 4/4)
	Central Nervous System - Delayed motor development [UMLS: C1854301 HPO: HP:0001270] [HPO: HP:0001270] - Delayed walking [UMLS: C0241726 HPO: HP:0031936] [HPO: HP:0031936] - Difficulty walking [SNOMEDCT: 228158008, 719232003] [ICD9CM: 719.7] [UMLS: C0311394 HPO: HP:0002355] [HPO: HP:0002355] - Inability to walk independently (rare) [UMLS: C2674510]	Central Nervous System - Hyperthermia [SNOMEDCT: 31847002, 1197782006, 50177009, 386661006] [ICD10CM: R50.9] [ICD9CM: 780.60] [UMLS: C5232927, C0203597, C0015967 HPO: HP:0001945] [HPO: HP:0001945]	Central Nervous System - Delayed motor development [UMLS: C1854301 HPO: HP:0001270] [HPO: HP:0001270] - Some patients only achieve sitting [UMLS: C3278546]	Central Nervous System - Delayed motor development [UMLS: C1854301 HPO: HP:0001270] [HPO: HP:0001270]
	Peripheral Nervous System - Hyporeflexia [SNOMEDCT: 22994000, 405946002] [UMLS: C0700078, C0151888 HPO: HP:0001315, HP:0001265] [HPO: HP:0001265] - Areflexia [SNOMEDCT: 37280007] [UMLS: C0234146 HPO: HP:0001284] [HPO: HP:0001284]		Peripheral Nervous System - Areflexia [SNOMEDCT: 37280007] [UMLS: C0234146 HPO: HP:0001284] [HPO: HP:0001284]

METABOLIC FEATURES (in 2/4)		- Mixed respiratory and metabolic acidosis [UMLS: C1840372 HPO: HP:0005967] [HPO: HP:0005967]		- Malignant hyperthermia [SNOMEDCT: 213026003, 405501007] [ICD10CM: T88.3] [ICD9CM: 995.86] [UMLS: C0024591 HPO: HP:0002047] [HPO: HP:0002047]
HEMATOLOGY (in 1/4)		- Coagulopathy [SNOMEDCT: 362970003, 64779008] [ICD10CM: D68.9] [ICD9CM: 286] [UMLS: C0005779 HPO: HP:0003256, HP:0001928] [HPO: HP:0003256]
PRENATAL MANIFESTATIONS (in 1/4)
			Movement - Reduced fetal movements [SNOMEDCT: 276369006] [ICD10CM: O36.81, O36.8190] [UMLS: C0235659 HPO: HP:0001558] [HPO: HP:0001558]
			Amniotic Fluid - Hydrops [SNOMEDCT: 79654002, 20741006, 267038008] [ICD10CM: R60.9] [ICD9CM: 782.3] [UMLS: C0013604, C1058427 HPO: HP:0000969] [HPO: HP:0000969] - Polyhydramnios [SNOMEDCT: 86203003] [ICD10CM: O40] [ICD9CM: 657.0, 657] [UMLS: C0020224 HPO: HP:0001561] [HPO: HP:0001561]



LABORATORY ABNORMALITIES (in 3/4)		- Elevated serum CPK [UMLS: C0241005 HPO: HP:0003236] [HPO: HP:0003236] - Hyperkalemia [SNOMEDCT: 238142003, 166689004, 14140009] [ICD10CM: E87.5] [ICD9CM: 276.7] [UMLS: C0020461, C5700154 HPO: HP:0002153] [HPO: HP:0002153] - Hyperphosphatemia [SNOMEDCT: 20165001] [UMLS: C0085681, C3665437 HPO: HP:0002905] [HPO: HP:0002905] - Myoglobinuria [SNOMEDCT: 48165008] [ICD10CM: R82.1] [ICD9CM: 791.3] [UMLS: C0027080 HPO: HP:0002913] [HPO: HP:0002913] - Diagnosis by exposing muscle biopsy to caffeine and/or halothane [UMLS: C1840366]	- Normal serum creatine kinase [UMLS: C1850678]	- Elevated serum creatine kinase, mild [UMLS: C5563471] [HPO: HP:0003236]
MISCELLANEOUS (in 4/4)	- Onset in infancy or early childhood - Nonprogressive or slowly progressive - Phenotypic variability [UMLS: C1837514 HPO: HP:0003812] [HPO: HP:0003812] - Findings in muscle biopsy may be variable - De novo mutation (in some patients) [UMLS: C2985439]	- Heterogeneous disorder - Precipitated by general anesthesia - Elevated body temperatures to 42 degrees celsius - Incidence of MH in anesthetized children is 1 in 15,000 - Incidence of MH in anesthetized adults is 1 in 50,000-100,000	- Onset in neonatal period or early infancy - Highly variable phenotype [UMLS: C1839039 HPO: HP:0003812] [HPO: HP:0003812] - Some patients have lethal fetal akinesia with death in utero - Findings in muscle biopsy may be variable	- Highly variable phenotype MOLECULAR BASIS Caused by mutation in the ryanodine receptor-1 gene (RYR1, 180901.0038)
MOLECULAR BASIS (in 3/4)	- Caused by mutation in the ryanodine receptor 1 gene (RYR1, 180901.0003)	- Caused by mutations in the ryanodine receptor gene (RYR1, 180901.0001)	- Caused by mutation in the ryanodine receptor-1 gene (RYR1, 180901.0021)