Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 1(SCAN1)

MedGen UID:: 1683470
•Concept ID:: C4759870
•: Disease or Syndrome

Synonym:	SCAN1
SNOMED CT:	Spinocerebellar ataxia with axonal neuropathy type 1 (765091006)
Modes of inheritance:	Autosomal recessive inheritance MedGen UID: 141025 •Concept ID: C0441748 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Autosomal recessive inheritance (Orphanet)

Gene (location): Gene(s) directly associated with this condition or phenotype.	TDP1 (14q32.11)

Monarch Initiative:	MONDO:0011801
OMIM®:	607250
Orphanet:	ORPHA94124

Disease characteristics

Excerpted from the GeneReview: Spinocerebellar Ataxia with Axonal Neuropathy Type 1

Spinocerebellar ataxia with axonal neuropathy type 1 (SCAN1) is characterized by late-childhood-onset slowly progressive cerebellar ataxia and distal sensorimotor axonal neuropathy. Gaze nystagmus and dysarthria usually develop after the onset of ataxic gait. As the disease advances, pain and touch sensation in the hands and feet become impaired; vibration sense is lost in hands and lower thighs. Individuals with advanced disease develop a steppage gait and pes cavus and eventually become wheelchair dependent. Cognitive dysfunction – present in some – manifests as mild intellectual disability and poor executive function. To date only seven affected individuals have been described from three apparently unrelated consanguineous families (one from Saudi Arabia and two from Oman); therefore, it is likely that the full phenotypic spectrum of this disorder is not yet known. [from GeneReviews]

Authors:
Mustafa AM Salih | Hiroshi Takashima | Cornelius F Boerkoel view full author information

Additional description

From OMIM
Spinocerebellar ataxia with axonal neuropathy-1 (SCAN1) is an autosomal recessive neurologic disorder characterized by onset of gait disturbances in the first or second decades of life. Affected individuals have cerebellar ataxia associated with cerebellar atrophy on brain imaging, as well as an axonal sensorimotor neuropathy with distal sensory impairment, hypo- or areflexia, pes cavus, and steppage gait (summary by Takashima et al., 2002). Genetic Heterogeneity of Spinocerebellar Ataxia with Axonal Neuropathy See also SCAN2 (606002), caused by mutation in the SETX gene (608465) on chromosome 9q34, and SCAN3 (618387), caused by mutation in the COA7 gene (615623) on chromosome 1p32. http://www.omim.org/entry/607250

Clinical features

From HPO

Pes cavus

MedGen UID:: 675590
•Concept ID:: C0728829
•: Congenital Abnormality

The presence of an unusually high plantar arch. Also called high instep, pes cavus refers to a distinctly hollow form of the sole of the foot when it is bearing weight.

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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).

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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.

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Seizure

MedGen UID:: 20693
•Concept ID:: C0036572
•: Sign or Symptom

A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.

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Sensory neuropathy

MedGen UID:: 101791
•Concept ID:: C0151313
•: Disease or Syndrome

Peripheral neuropathy affecting the sensory nerves.

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Areflexia

MedGen UID:: 115943
•Concept ID:: C0234146
•: Finding

Absence of neurologic reflexes such as the knee-jerk reaction.

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Cerebral atrophy

MedGen UID:: 116012
•Concept ID:: C0235946
•: Disease or Syndrome

Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.

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Steppage gait

MedGen UID:: 98105
•Concept ID:: C0427149
•: Finding

An abnormal gait pattern that arises from weakness of the pretibial and peroneal muscles due to a lower motor neuron lesion. Affected patients have footdrop and are unable to dorsiflex and evert the foot. The leg is lifted high on walking so that the toes clear the ground, and there may be a slapping noise when the foot strikes the ground again.

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Hyporeflexia

MedGen UID:: 195967
•Concept ID:: C0700078
•: Finding

Reduction of neurologic reflexes such as the knee-jerk reaction.

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Cerebellar atrophy

MedGen UID:: 196624
•Concept ID:: C0740279
•: Disease or Syndrome

Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.

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Peripheral axonal neuropathy