Ataxia, and Pes planus

• Intellectual disability
• Seizures
• Global developmental delay
• Microcephaly
• Ataxia

SOURCES: OMIM MENDELIAN

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

Autosomal recessive congenital cerebellar ataxia due to MGLUR1 deficiency is a rare, genetic, slowly progressive neurodegenerative disease resulting from MGLUR1 deficiency characterized by global developmental delay (beginning in infancy), mild to severe intellectual deficit with poor or absent speech, moderate to severe stance and gait ataxia, pyramidal signs (e.g. hyperreflexia) and mild dysdiadochokinesia, dysmetria, tremors, and/or dysarthria. Oculomotor signs, such as nystagmus, strabismus, ptosis and hypometric saccades, may also be associated. Brain imaging reveals progressive, generalized, moderate to severe cerebellar atrophy, inferior vermian hypoplasia, and/or constitutionally small brain.

AUTOSOMAL RECESSIVE CONGENITAL CEREBELLAR ATAXIA DUE TO MGLUR1 DEFICIENCY Is also known as autosomal recessive spinocerebellar ataxia type 13|scar13|autosomal recessive congenital cerebellar ataxia due to metabotropic glutamate receptor 1 deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: ORPHANET OMIM MENDELIAN

Dysequilibrium syndrome (DES) is a non-progressive cerebellar disorder characterized by ataxia associated with an intellectual disability, delayed ambulation and cerebellar hypoplasia.

DYSEQUILIBRIUM SYNDROME Is also known as cerebellar ataxia-intellectual disability-dysequilibrium syndrome syndrome|cerebellar hypoplasia, vldlr-associated|non-progressive cerebellar ataxia-intellectual disability syndrome|cerebellar ataxia and mental retardation with or without quadrupedal loco

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: OMIM ORPHANET MENDELIAN

Charcot-Marie-Tooth disease type 4B3 (CMT4B3) is a subtype of Charcot-Marie-Tooth type 4 characterized by a childhood onset of slowly progressing, demyelinating sensorimotor neuropathy, focally folded myelin sheaths in nerve biopsy, reduced nerve conduction velocities (less than 38 m/s), and the typical CMT phenotype (i.e. distal muscle weakness and atrophy, and sensory loss).

CHARCOT-MARIE-TOOTH DISEASE TYPE 4B3 Is also known as charcot-marie-tooth disease with focally folded myelin|cmt4b3

• Intellectual disability
• Microcephaly
• Scoliosis
• Ataxia
• Strabismus

SOURCES: OMIM ORPHANET MENDELIAN

Early-onset progressive neurodegeneration-blindness-ataxia-spasticity syndrome is a genetic neurodegenerative disease characterized by normal early development followed by childhood onset optic atrophy with progressive vision loss and eventually blindness, followed by progressive neurological decline that typically includes cerebellar ataxia, nystagmus, dorsal column dysfunction (decreased vibration and position sense), spastic paraplegia and finally tetraparesis.

EARLY-ONSET PROGRESSIVE NEURODEGENERATION-BLINDNESS-ATAXIA-SPASTICITY SYNDROME Is also known as ndgoa|neurodegeneration with optic atrophy, childhood-onset

• Seizures
• Ataxia
• Nystagmus
• Spasticity
• Cognitive impairment

SOURCES: ORPHANET OMIM MENDELIAN

Distal arthrogryposis with impaired proprioception and touch is an autosomal recessive neurologic disorder characterized by loss of certain mechanosensation modalities resulting in ataxia, difficulty walking, dysmetria, muscle weakness and atrophy, and progressive skeletal contractures. Patients have onset of symptoms in early childhood (summary by Chesler et al., 2016 and Delle Vedove et al., 2016).

• Short stature
• Generalized hypotonia
• Scoliosis
• Ataxia
• Muscle weakness

SOURCES: OMIM MENDELIAN

The congenital variant of Rett syndrome is a severe neurodevelopmental disorder with features of classic Rett syndrome (RTT ), but earlier onset in the first months of life. Classic Rett syndrome shows later onset and is caused by mutation in the MECP2 gene (OMIM ).

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

SOURCES: OMIM MENDELIAN

NEDMIAL is a neurodevelopmental disorder characterized by severely delayed psychomotor development and hypotonia apparent from early infancy, resulting in feeding difficulties, ataxic gait or inability to walk, minimal or absent speech development, and severe intellectual disability, often with behavioral abnormalities, such as hand-flapping. Additional common features may include sleep disorder, nonspecific dysmorphic facial features, and joint hyperlaxity (summary by Lessel et al., 2017).

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment

SOURCES: OMIM MENDELIAN

The disorders involving primarily the cerebellar parenchyma have been classified into six forms. In cerebelloparenchymal disorder III, cerebellar ataxia is congenital (non-progressive) and characterized by cerebellar symptoms such as incoordination of gait often associated with poor coordination of hands, speech and eye movements. The other features are congenital mental retardation and hypotonia, in addition to other neurological and non-neurological features. MRI or CT scan show marked atrophy of the vermis and hemispheres. A severe loss of granule cells with heterotopic Purkinje cells is observed. The mode of inheritance in the few reported families is autosomal recessive. In one family, cerebellar ataxia was associated to albinism.: In a large inbred Lebanese family the disease locus was assigned to a 12.1-cM interval on chromosome 9q34-qter between markers D9S67 and D9S312. The primary biochemical defect remains unknown. Up to now, the only treatment has consisted in early interventional therapies including intensive speech therapy and adequate stimulation and/or training.

AUTOSOMAL RECESSIVE CEREBELLOPARENCHYMAL DISORDER TYPE 3 Is also known as cpd iii|scar2|cpd3|cerebellar granular cell hypoplasia and mental retardation, congenital|autosomal recessive spinocerebellar ataxia type 2|cerebellar hypoplasia, nonprogressive norman type|cerebelloparenchymal disorder iii

• Intellectual disability
• Global developmental delay
• Short stature
• Generalized hypotonia
• Hearing impairment

SOURCES: OMIM MESH ORPHANET MENDELIAN