Ataxia, and Generalized muscle weakness

Dejerine-Sottas neuropathy is a demyelinating peripheral neuropathy with onset in infancy. It can show autosomal dominant or recessive inheritance. Affected individuals have delayed motor development due to severe distal motor and sensory impairment, resulting in difficulties in gait. Some patients have generalized hypotonia in infancy. Other features may include pes cavus, scoliosis, and sensory ataxia. Nerve conduction velocities are severely decreased (sometimes less than 10 m/s), and sural nerve biopsy shows severe loss of myelinated fibers (summary by Baets et al., 2011).

HYPERTROPHIC NEUROPATHY OF DEJERINE-SOTTAS Is also known as hereditary motor and sensory neuropathy type iii|dsn|hmsn3|dss|dejerine-sottas syndrome|cmt3|charcot-marie-tooth disease, type 3|dejerine-sottas neuropathy

• Generalized hypotonia
• Scoliosis
• Ataxia
• Nystagmus
• Muscle weakness

SOURCES: OMIM MENDELIAN

Charcot-Marie-Tooth disease type 4C (CMT4C) is a subtype of Charcot-Marie-Tooth type 4 characterized by childhood or adolescent-onset of a relatively mild, demyelinating sensorimotor neuropathy that contrasts with a severe, rapidly progressing, early-onset scoliosis, and the typical CMT phenotype (i.e. distal muscle weakness and atrophy, sensory loss, and often foot deformity). A wide spectrum of nerve conduction velocities are observed and cranial nerve involvement and kyphoscoliosis have also been reported.

CHARCOT-MARIE-TOOTH DISEASE TYPE 4C Is also known as charcot-marie-tooth disease, demyelinating, autosomal recessive, type 4c|charcot-marie-tooth neuropathy, type 4c|cmt4c

• Hearing impairment
• Scoliosis
• Ataxia
• Nystagmus
• Muscle weakness

SOURCES: ORPHANET MESH OMIM MENDELIAN

Paroxysmal non-kinesigenic dyskinesia (PNKD) is a form of paroxysmal dyskinesia (see this term), characterized by attacks of dystonic or choreathetotic movements precipitated by stress, fatigue, coffee or alcohol intake or menstruation.

PAROXYSMAL NON-KINESIGENIC DYSKINESIA Is also known as paroxysmal dystonic choreoathetosis|choreoathetosis, nonkinesigenic|pdc|dystonia 8|paroxystic non-kinesigenic choreoathetosis|dyt8|choreoathetosis, familial paroxysmal|mount-reback syndrome|fpd1

• Seizures
• Ataxia
• Spasticity
• Dysarthria
• Fatigue

SOURCES: OMIM ORPHANET MENDELIAN

Mitochondrial DNA depletion syndrome-8A is a severe autosomal recessive disorder characterized by neonatal hypotonia, lactic acidosis, and neurologic deterioration. Renal tubular involvement may also occur (Bourdon et al., 2007).Mitochondrial DNA depletion syndrome-8B is characterized by ophthalmoplegia, ptosis, gastrointestinal dysmotility, cachexia, peripheral neuropathy, and brain MRI changes, known as the MNGIE phenotype (Shaibani et al., 2009).For a discussion of genetic heterogeneity of mtDNA depletion syndromes, see MTDPS1 (OMIM ).

MITOCHONDRIAL DNA DEPLETION SYNDROME, ENCEPHALOMYOPATHIC FORM WITH RENAL TUBULOPATHY Is also known as mitochondrial dna depletion syndrome, encephalomyopathic, with renal tubulopathy, autosomal recessive|mtdna depletion syndrome, encephalomyopathic form with renal tubulopathy

• Intellectual disability
• Seizures
• Generalized hypotonia
• Hearing impairment
• Failure to thrive

SOURCES: ORPHANET OMIM MENDELIAN

Mitochondrial DNA depletion syndrome-4B is an autosomal recessive progressive multisystem disorder clinically characterized by chronic gastrointestinal dysmotility and pseudoobstruction, cachexia, progressive external ophthalmoplegia (PEO), axonal sensory ataxic neuropathy, and muscle weakness (van Goethem et al., 2003).For a discussion of genetic heterogeneity of autosomal recessive mtDNA depletion syndromes, see MTDPS1 (OMIM ).

MITOCHONDRIAL DNA DEPLETION SYNDROME 4B (MNGIE TYPE); MTDPS4B Is also known as mngie, polg-related|mitochondrial neurogastrointestinal encephalopathy syndrome, polg-related

• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia
• Hearing impairment

SOURCES: OMIM MENDELIAN

PCH11 is an autosomal recessive neurodevelopmental disorder characterized by severely delayed psychomotor development with intellectual disability and poor speech, microcephaly, dysmorphic features, and pontocerebellar hypoplasia on brain imaging. Additional features are more variable (summary by Marin-Valencia et al., 2017).For a general phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (OMIM ).

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly

SOURCES: OMIM MENDELIAN

Episodic ataxia is a genetically heterogeneous neurologic condition characterized by spells of incoordination and imbalance, often associated with progressive ataxia. Episodic ataxia type 2 is the most common form of EA (Jen et al., 2007).For a discussion of genetic heterogeneity of episodic ataxia, see EA1 (OMIM ).

EPISODIC ATAXIA, TYPE 2; EA2 Is also known as cerebellopathy, hereditary paroxysmal|ataxia, familial paroxysmal|capa|acetazolamide-responsive hereditary paroxysmal cerebellar ataxia|apca|cerebellar ataxia, paroxysmal, acetazolamide-responsive|ataxia, episodic, with nystagmus|episodic ataxia, nystagmu

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Scoliosis

SOURCES: OMIM MENDELIAN

Vestibular schwannoma is a rare tumor of the posterior fossa originating in the Schwann cells of the vestibular transitional zone of the vestibulocochlear nerve that can be benign, small, slow growing and asymptomatic or large, faster growing and aggressive and potentially fatal, presenting with symptoms of hearing and balance impairment, vertigo, ataxia, headache and fifth, sixth or seventh cranial nerve dysfunction and facial numbness.

VESTIBULAR SCHWANNOMA Is also known as bilateral acoustic neurofibromatosis|acoustic neurilemoma|acoustic schwannomas, bilateral|banf|neurofibromatosis, central type|acoustic neurinoma|acn|acoustic neuroma|acoustic neurinoma, bilateral

• Seizures
• Hearing impairment
• Ataxia
• Neoplasm
• Sensorineural hearing impairment

SOURCES: ORPHANET OMIM MENDELIAN

DLD deficiency is an autosomal recessive metabolic disorder characterized biochemically by a combined deficiency of the branched-chain alpha-keto acid dehydrogenase complex (BCKDC), pyruvate dehydrogenase complex (PDC), and alpha-ketoglutarate dehydrogenase complex (KGDC). This is the result of E3 being a common component of all 3 mitochondrial multienzyme complexes. Clinically, affected individuals have lactic acidosis and neurologic deterioration due to sensitivity of the central nervous system to defects in oxidative metabolism. E3 deficiency is often associated with increased urinary excretion of alpha-keto acids, such as pyruvate (summary by Hong et al., 1996). E3 deficiency can also be associated with increased concentrations of branched-chain amino acids, as observed in maple syrup urine disease (MSUD ), and is sometimes referred to as 'MSUD type III,' although patients with E3 deficiency have additional biochemical defects (Chuang and Shih, 2001; Robinson, 2001).

DIHYDROLIPOAMIDE DEHYDROGENASE DEFICIENCY; DLDD Is also known as maple syrup urine disease, type iii|e3 deficiency|lipoamide dehydrogenase deficiency, lactic acidosis due to|dld deficiency

• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Microcephaly

SOURCES: OMIM MENDELIAN

Kufor-Rakeb syndrome (KRS) is a rare genetic neurodegenerative disorder characterized by juvenile Parkinsonism, pyramidal degeneration (dystonia), supranuclear palsy, and cognitive impairment.

KUFOR-RAKEB SYNDROME Is also known as parkinson disease 9, autosomal recessive, juvenile-onset|park9|pallidopyramidal degeneration with supranuclear upgaze paresis and dementia|krppd

• Intellectual disability
• Seizures
• Ataxia
• Nystagmus
• Spasticity

SOURCES: OMIM ORPHANET MENDELIAN