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Spastic paraplegia 81, autosomal recessive(SPG81)

MedGen UID:
1711668
Concept ID:
C5394033
Disease or Syndrome
Synonyms: SPASTIC PARAPLEGIA 81, AUTOSOMAL RECESSIVE; SPG81
 
Gene (location): SELENOI (2p23.3)
 
Monarch Initiative: MONDO:0032905
OMIM®: 618768

Definition

Spastic paraplegia-81 (SPG81) is an autosomal recessive neurologic disorder with onset in infancy. Affected individuals have delayed motor development, progressive spasticity, and other neurologic impairment, including impaired intellectual development and speech delay. Some patients may have additional features, including bifid uvula, microcephaly, seizures, and variable ocular anomalies. One severely affected patient was reported to have cortical visual loss, sensorineural deafness, and achievement of almost no developmental milestones. Brain imaging shows white matter abnormalities, hypomyelination with progressive white matter loss, and sometimes cerebral atrophy. These significant additional abnormalities enable classification of this disorder as a complicated form of SPG (summary by Ahmed et al., 2017 and Horibata et al., 2018). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800). [from OMIM]

Clinical features

From HPO
Ankle clonus
MedGen UID:
68672
Concept ID:
C0238651
Finding
Clonus is an involuntary tendon reflex that causes repeated flexion and extension of the foot. Ankle clonus is tested by rapidly flexing the foot upward.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
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.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Babinski sign
MedGen UID:
19708
Concept ID:
C0034935
Finding
Upturning of the big toe (and sometimes fanning of the other toes) in response to stimulation of the sole of the foot. If the Babinski sign is present it can indicate damage to the corticospinal tract.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Inability to walk
MedGen UID:
107860
Concept ID:
C0560046
Finding
Incapability to ambulate.
Lower limb spasticity
MedGen UID:
220865
Concept ID:
C1271100
Finding
Spasticity (velocity-dependent increase in tonic stretch reflexes with increased muscle tone and hyperexcitable tendon reflexes) in the muscles of the lower limbs, hips, and pelvis.
Upper limb spasticity
MedGen UID:
220882
Concept ID:
C1273957
Finding
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Motor regression
MedGen UID:
478627
Concept ID:
C3276997
Finding
Loss of previously achieved motor skills, as manifested by loss of developmental motor milestones.
Periventricular white matter hyperintensities
MedGen UID:
927595
Concept ID:
C4293686
Finding
Areas of brighter than expected signal on magnetic resonance imaging emanating from the cerebral white matter that surrounds the cerebral ventricles.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Bifid uvula
MedGen UID:
1646931
Concept ID:
C4551488
Congenital Abnormality
Uvula separated into two parts most easily seen at the tip.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Reduced visual acuity
MedGen UID:
65889
Concept ID:
C0234632
Finding
Diminished clarity of vision.
Retinal vascular tortuosity
MedGen UID:
349827
Concept ID:
C1860475
Anatomical Abnormality
The presence of an increased number of twists and turns of the retinal blood vessels.
Cerebral visual impairment
MedGen UID:
890568
Concept ID:
C4048268
Pathologic Function
A form of loss of vision caused by damage to the visual cortex rather than a defect in the eye.

Recent clinical studies

Etiology

Pedroso JL, Vale TC, Freitas JL, Araújo FMM, Meira AT, Neto PB, França MC Junior, Tumas V, Teive HAG, Barsottini OGP
Arq Neuropsiquiatr 2023 Nov;81(11):1000-1007. Epub 2023 Nov 30 doi: 10.1055/s-0043-1777005. PMID: 38035585Free PMC Article
Garaci F, Toschi N, Lanzafame S, Meschini A, Bertini E, Simonetti G, Santorelli FM, Guerrisi M, Floris R
Int J Neurosci 2014 Apr;124(4):261-70. Epub 2013 Sep 27 doi: 10.3109/00207454.2013.836705. PMID: 23968121
de Bot ST, van den Elzen RT, Mensenkamp AR, Schelhaas HJ, Willemsen MA, Knoers NV, Kremer HP, van de Warrenburg BP, Scheffer H
J Neurol Neurosurg Psychiatry 2010 Oct;81(10):1073-8. Epub 2010 Jun 20 doi: 10.1136/jnnp.2009.201103. PMID: 20562464

Diagnosis

Pedroso JL, Vale TC, Freitas JL, Araújo FMM, Meira AT, Neto PB, França MC Junior, Tumas V, Teive HAG, Barsottini OGP
Arq Neuropsiquiatr 2023 Nov;81(11):1000-1007. Epub 2023 Nov 30 doi: 10.1055/s-0043-1777005. PMID: 38035585Free PMC Article
Lilley K, Bhuta S, Sabet A, Broadley SA
J Clin Neurosci 2020 Nov;81:90-91. Epub 2020 Sep 29 doi: 10.1016/j.jocn.2020.09.004. PMID: 33222977
Garaci F, Toschi N, Lanzafame S, Meschini A, Bertini E, Simonetti G, Santorelli FM, Guerrisi M, Floris R
Int J Neurosci 2014 Apr;124(4):261-70. Epub 2013 Sep 27 doi: 10.3109/00207454.2013.836705. PMID: 23968121

Clinical prediction guides

Pedroso JL, Vale TC, Freitas JL, Araújo FMM, Meira AT, Neto PB, França MC Junior, Tumas V, Teive HAG, Barsottini OGP
Arq Neuropsiquiatr 2023 Nov;81(11):1000-1007. Epub 2023 Nov 30 doi: 10.1055/s-0043-1777005. PMID: 38035585Free PMC Article
Thal DR, Züchner S, Gierer S, Schulte C, Schöls L, Schüle R, Synofzik M
Int J Mol Sci 2015 Oct 21;16(10):25050-66. doi: 10.3390/ijms161025050. PMID: 26506339Free PMC Article
Garaci F, Toschi N, Lanzafame S, Meschini A, Bertini E, Simonetti G, Santorelli FM, Guerrisi M, Floris R
Int J Neurosci 2014 Apr;124(4):261-70. Epub 2013 Sep 27 doi: 10.3109/00207454.2013.836705. PMID: 23968121

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