Ataxia, and Myopathy

Low match NONAKA MYOPATHY; NM

NONAKA MYOPATHY; NM Is also known as myopathy, distal, with or without rimmed vacuoles|gne myopathy|inclusion body myopathy 2, autosomal recessive, formerly|ibm2, formerly|hibm|nonaka distal myopathy|inclusion body myopathy, quadriceps-sparing|qsm|inclusion body myopathy, hereditary, autosom

• Ataxia
• Muscle weakness
• Gait disturbance
• Myopathy
• Elevated serum creatine phosphokinase

SOURCES: OMIM MENDELIAN

Low match LOWER MOTOR NEURON SYNDROME WITH LATE-ADULT ONSET

The Jokela type of spinal muscular atrophy (SMAJ) is an autosomal dominant lower motor neuron disorder characterized by adult-onset of muscle cramps and fasciculations affecting the proximal and distal muscles of the upper and lower limbs. The disorder is slowly progressive, resulting in weakness and mild muscle atrophy later in life (summary by Jokela et al., 2011).

• Ataxia
• Muscle weakness
• Skeletal muscle atrophy
• Tremor
• Gait disturbance

SOURCES: ORPHANET OMIM MENDELIAN

Low match PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT 5; PEOA5

PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT 5; PEOA5 Is also known as progressive external ophthalmoplegia, autosomal dominant 5

• Hearing impairment
• Ataxia
• Ptosis
• Dysarthria
• Fatigue

SOURCES: MESH OMIM MENDELIAN

Low match USHER SYNDROME, TYPE IIIB; USH3B

Usher syndrome type III is characterized by postlingual, progressive hearing loss, variable vestibular dysfunction, and onset of retinitis pigmentosa symptoms, including nyctalopia, constriction of the visual fields, and loss of central visual acuity, usually by the second decade of life (Karjalainen et al., 1985; Pakarinen et al., 1995).For a discussion of genetic heterogeneity of type III Usher syndrome, see USH3A (OMIM ).

• Hearing impairment
• Ataxia
• Nystagmus
• Visual impairment
• Myopathy

SOURCES: OMIM MENDELIAN

Low match FAMILIAL DILATED CARDIOMYOPATHY WITH CONDUCTION DEFECT DUE TO LMNA MUTATION

Familial dilated cardiomyopathy with conduction defect due to LMNA mutation is a rare familial dilated cardiomyopathy characterized by left ventricular enlargement and/or reduced systolic function preceded or accompanied by significant conduction system disease and/or arrhythmias including bradyarrhythmias, supraventricular or ventricular arrhythmias. Disease onset is usually in early to mid-adulthood. Sudden cardiac death may occur and may be the presenting symptom. In some cases, it is associated with skeletal myopathy and elevated serum creatine kinase.

FAMILIAL DILATED CARDIOMYOPATHY WITH CONDUCTION DEFECT DUE TO LMNA MUTATION Is also known as cardiomyopathy, familial idiopathic|cardiomyopathy, idiopathic dilated|cardiomyopathy, dilated, with conduction defect 1|cdcd1|cardiomyopathy, congestive

• Ataxia
• Pain
• Fatigue
• Ventriculomegaly
• Cardiomyopathy

SOURCES: ORPHANET OMIM MENDELIAN

Low match CHARCOT-MARIE-TOOTH DISEASE, DOMINANT INTERMEDIATE G; CMTDIG

CMTDIG is an autosomal dominant neurologic disorder with a highly variable phenotype. Most affected individuals have onset in the first or second decades of slowly progressive distal motor weakness and atrophy, resulting in gait instability and distal upper limb impairment, as well as distal sensory impairment. More severely affected individuals may have pes cavus and claw hands and become wheelchair-bound, whereas other affected individuals have later onset with a milder disease course. Electrophysiologic studies tend to show median motor nerve conduction velocities (NCV) in the 'intermediate' range, between 25 and 45 m/s (summary by Berciano et al., 2017).In a review of intermediate CMT, Berciano et al. (2017) noted that advanced axonal degeneration may induce secondary demyelinating changes resulting in decreased NCV and attenuated compound muscle action potential (CMAP) in median nerve conduction studies. They thus suggested that testing the upper arm, axilla to elbow, may provide more accurate assessment of NCV and CMAP and reveal an intermediate phenotype (review by Berciano et al., 2017).For a discussion of genetic heterogeneity of CMTDI, see {606482}.

• Generalized hypotonia
• Hearing impairment
• Ataxia
• Nystagmus
• Muscle weakness

SOURCES: OMIM MENDELIAN

Low match FRONTOTEMPORAL DEMENTIA AND/OR AMYOTROPHIC LATERAL SCLEROSIS 2; FTDALS2

• Hearing impairment
• Ataxia
• Sensorineural hearing impairment
• Muscle weakness
• Ptosis

SOURCES: OMIM MENDELIAN

Low match CONGENITAL FIBROSIS OF EXTRAOCULAR MUSCLES

Congenital fibrosis of the extraocular muscles (CFEOM) encompasses several different inherited strabismus syndromes characterized by congenital restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. Classic CFEOM is characterized by bilateral blepharoptosis and ophthalmoplegia with the eyes fixed in an infraducted position about 20 to 30 degrees below the horizontal midline. Involvement of the horizontal extraocular muscles is variable. If all affected members of a family have the classic phenotype with bilateral involvement, the disorder is referred to as 'CFEOM1' (Engle et al., 1997; Heidary et al., 2008).CFEOM2 (OMIM ), an autosomal recessive disorder caused by mutation in the ARIX gene (OMIM ) on chromosome 11q13, is characterized by bilateral ptosis with eyes fixed in an exotropic position.The CFEOM3 phenotype shows more variable clinical features: affected individuals may have unilateral eye involvement, may be able raise their eyes above midline, or may not have blepharoptosis. CFEOM3 is diagnosed in a family if even 1 member does not have classic findings of the disorder. CFEOM3 is a genetically heterogeneous disorder; CFEOM3A with or without extraocular involvement (OMIM ) is caused by mutation in the TUBB3 gene (OMIM ) on chromosome 16q24; CFEOM3B is caused by mutation in the KIF21A gene (OMIM ) on chromosome 12q12; and CFEOM3C (OMIM ) maps to chromosome 13q.CFEOM4 (OMIM ), also known as Tukel syndrome, maps to chromosome 21q.CFEOM5 (OMIM ) is caused by mutation in the COL25A1 gene (OMIM ) on chromosome 4q25.See also NOMENCLATURE below.

CONGENITAL FIBROSIS OF EXTRAOCULAR MUSCLES Is also known as feom|feom1 locus|ophthalmoplegia, congenital|blepharoptosis with absent eye movements

• Intellectual disability
• Ataxia
• Strabismus
• Ptosis
• Optic atrophy

SOURCES: OMIM ORPHANET MENDELIAN

Low match OPTIC ATROPHY 1; OPA1

Autosomal dominant optic atrophy is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disc pallor, color vision deficits, and centrocecal scotoma of variable density (Votruba et al., 1998).Some patients with mutations in the OPA1 gene may also develop extraocular neurologic features, such as deafness, progressive external ophthalmoplegia, muscle cramps, hyperreflexia, and ataxia; see {125250}. There appears to be a wide range of intermediate phenotypes (Yu-Wai-Man et al., 2010).Yu-Wai-Man et al. (2009) provided a detailed review of autosomal dominant optic atrophy and Leber hereditary optic neuropathy (LHON ), with emphasis on the selective vulnerability of retinal ganglion cells to mitochondrial dysfunction in both disorders. Genetic Heterogeneity of Optic AtrophyOptic atrophy-2 (OPA2 ) maps to chromosome Xp11.4-p11.21. OPA3 (OMIM ) is caused by mutation in the OPA3 gene (OMIM ) on chromosome 19q13. OPA4 (OMIM ) maps to chromosome 18q12.2-q12.3. OPA5 (OMIM ) is caused by mutation in the DNM1L gene (OMIM ) on chromosome 12p11. OPA6 (OMIM ) maps to chromosome 8q21-q22. OPA7 (OMIM ) is caused by mutation in the TMEM126A gene (OMIM ) on chromosome 11q14. OPA8 (OMIM ) maps to chromosome 16q21-q22. OPA9 (OMIM ) is caused by mutation in the ACO2 gene (OMIM ) on chromosome 22q13; OPA10 (OMIM ) is caused by mutation in the RTN4IP1 gene (OMIM ) on chromosome 6q21; and OPA11 (OMIM ) is caused by mutation in the YME1L1 gene (OMIM ) on chromosome 10p12.

OPTIC ATROPHY 1; OPA1 Is also known as kjer-type optic atrophy|optic atrophy, kjer type|oak|optic atrophy, juvenile

• Hearing impairment
• Ataxia
• Strabismus
• Sensorineural hearing impairment
• Visual impairment

SOURCES: ORPHANET OMIM MENDELIAN

Low match MITOCHONDRIAL MYOPATHY-LACTIC ACIDOSIS-DEAFNESS SYNDROME

Mitochondrial myopathy-lactic acidosis-deafness is a type of metabolic myopathy described only in two sisters to date, presenting during childhood, and characterized clinically by growth failure, severe muscle weakness, and moderate sensorineural deafness and biochemically by metabolic acidosis, elevated serum pyruvate concentration, hyperalaninemia and hyperalaninuria. There have been no further descriptions in the literature since 1973.

MITOCHONDRIAL MYOPATHY-LACTIC ACIDOSIS-DEAFNESS SYNDROME Is also known as mitochondrial myopathy-lactic acidosis-hearing loss syndrome

• Seizures
• Generalized hypotonia
• Sensorineural hearing impairment
• Muscle weakness
• Spasticity

SOURCES: OMIM ORPHANET MENDELIAN