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Spastic paraplegia 85, autosomal recessive(SPG85)

MedGen UID:
1794263
Concept ID:
C5562053
Disease or Syndrome
Synonym: SPG85
 
Gene (location): RNF170 (8p11.21)
 
Monarch Initiative: MONDO:0030512
OMIM®: 619686

Definition

Autosomal recessive spastic paraplegia-85 (SPG85) is a neurologic disorder characterized by the onset of motor symptoms in the first few years of life. Affected individuals have spasticity and hyperreflexia of the lower limbs resulting in gait abnormalities. Older patients may have upper limb involvement and demonstrate axonal polyneuropathy. Additional features include optic atrophy, dysarthria, dysphagia, ataxia, and urinary incontinence. Brain imaging may show cerebellar atrophy (summary by Wagner et al., 2019). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800). [from OMIM]

Clinical features

From HPO
Urinary incontinence
MedGen UID:
22579
Concept ID:
C0042024
Finding
Loss of the ability to control the urinary bladder leading to involuntary urination.
Lower limb muscle weakness
MedGen UID:
324478
Concept ID:
C1836296
Finding
Weakness of the muscles of the legs.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
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.
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.
Spastic paraplegia
MedGen UID:
20882
Concept ID:
C0037772
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
Torticollis
MedGen UID:
11859
Concept ID:
C0040485
Sign or Symptom
Torticollis is a twisted neck as a result of shortening of sternocleidomastoid muscle. This short and fibrotic muscle pulls the head laterally and rotates the chin and face to the opposite end. Facial asymmetry may be a manifestation (summary by Engin et al., 1997).
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.
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
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
Impaired vibratory sensation
MedGen UID:
220959
Concept ID:
C1295585
Finding
A decrease in the ability to perceive vibration. Clinically, this is usually tested with a tuning fork which vibrates at 128 Hz and is applied to bony prominences such as the malleoli at the ankles or the metacarpal-phalangeal joints. There is a slow decay of vibration from the tuning fork. The degree of vibratory sense loss can be crudely estimated by counting the number of seconds that the examiner can perceive the vibration longer than the patient.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Impaired proprioception
MedGen UID:
346424
Concept ID:
C1856691
Finding
A loss or impairment of the sensation of the relative position of parts of the body and joint position.
Brisk reflexes
MedGen UID:
382164
Concept ID:
C2673700
Finding
Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal.
Impaired tactile sensation
MedGen UID:
866866
Concept ID:
C4021221
Finding
A reduced sense of touch (tactile sensation). This is usually tested with a wisp of cotton or a fine camel's hair brush, by asking patients to say 'now' each time they feel the stimulus.
Impaired temperature sensation
MedGen UID:
866867
Concept ID:
C4021222
Finding
A reduced ability to discriminate between different temperatures.
Generalized amyotrophy
MedGen UID:
234650
Concept ID:
C1389113
Disease or Syndrome
Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles.
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.
Saccadic smooth pursuit
MedGen UID:
373096
Concept ID:
C1836479
Finding
An abnormality of tracking eye movements in which smooth pursuit is interrupted by an abnormally high number of saccadic movements.

Recent clinical studies

Etiology

Fereshtehnejad SM, Saleh PA, Oliveira LM, Patel N, Bhowmick S, Saranza G, Kalia LV
Neurol Sci 2023 Mar;44(3):947-959. Epub 2022 Nov 28 doi: 10.1007/s10072-022-06516-8. PMID: 36441344Free PMC Article
Liao X, Luo Y, Zhan Z, Du J, Hu Z, Wang J, Guo J, Hu Z, Yan X, Pan Q, Xia K, Tang B, Shen L
Clin Genet 2015;87(1):85-9. Epub 2014 Jan 26 doi: 10.1111/cge.12336. PMID: 24359114
Shimazaki H, Honda J, Naoi T, Namekawa M, Nakano I, Yazaki M, Nakamura K, Yoshida K, Ikeda S, Ishiura H, Fukuda Y, Takahashi Y, Goto J, Tsuji S, Takiyama Y
J Neurol Neurosurg Psychiatry 2014 Sep;85(9):1024-8. Epub 2014 Feb 12 doi: 10.1136/jnnp-2013-306981. PMID: 24521565
Bettencourt C, López-Sendón JL, García-Caldentey J, Rizzu P, Bakker IM, Shomroni O, Quintáns B, Dávila JR, Bevova MR, Sobrido MJ, Heutink P, de Yébenes JG
Clin Genet 2014 Feb;85(2):154-8. Epub 2013 Mar 25 doi: 10.1111/cge.12133. PMID: 23438842
Baets J, Deconinck T, Smets K, Goossens D, Van den Bergh P, Dahan K, Schmedding E, Santens P, Rasic VM, Van Damme P, Robberecht W, De Meirleir L, Michielsens B, Del-Favero J, Jordanova A, De Jonghe P
Neurology 2010 Sep 28;75(13):1181-8. doi: 10.1212/WNL.0b013e3181f4d86c. PMID: 20876471

Diagnosis

Fereshtehnejad SM, Saleh PA, Oliveira LM, Patel N, Bhowmick S, Saranza G, Kalia LV
Neurol Sci 2023 Mar;44(3):947-959. Epub 2022 Nov 28 doi: 10.1007/s10072-022-06516-8. PMID: 36441344Free PMC Article
Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Shimazaki H, Honda J, Naoi T, Namekawa M, Nakano I, Yazaki M, Nakamura K, Yoshida K, Ikeda S, Ishiura H, Fukuda Y, Takahashi Y, Goto J, Tsuji S, Takiyama Y
J Neurol Neurosurg Psychiatry 2014 Sep;85(9):1024-8. Epub 2014 Feb 12 doi: 10.1136/jnnp-2013-306981. PMID: 24521565
Benez MD, Fontenelle E, Tozzi BB, Presotto C
An Bras Dermatol 2010 Nov-Dec;85(6):951-3. doi: 10.1590/s0365-05962010000600033. PMID: 21308331
Baets J, Deconinck T, Smets K, Goossens D, Van den Bergh P, Dahan K, Schmedding E, Santens P, Rasic VM, Van Damme P, Robberecht W, De Meirleir L, Michielsens B, Del-Favero J, Jordanova A, De Jonghe P
Neurology 2010 Sep 28;75(13):1181-8. doi: 10.1212/WNL.0b013e3181f4d86c. PMID: 20876471

Therapy

Benez MD, Fontenelle E, Tozzi BB, Presotto C
An Bras Dermatol 2010 Nov-Dec;85(6):951-3. doi: 10.1590/s0365-05962010000600033. PMID: 21308331

Prognosis

Liao X, Luo Y, Zhan Z, Du J, Hu Z, Wang J, Guo J, Hu Z, Yan X, Pan Q, Xia K, Tang B, Shen L
Clin Genet 2015;87(1):85-9. Epub 2014 Jan 26 doi: 10.1111/cge.12336. PMID: 24359114

Clinical prediction guides

Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Shimazaki H, Honda J, Naoi T, Namekawa M, Nakano I, Yazaki M, Nakamura K, Yoshida K, Ikeda S, Ishiura H, Fukuda Y, Takahashi Y, Goto J, Tsuji S, Takiyama Y
J Neurol Neurosurg Psychiatry 2014 Sep;85(9):1024-8. Epub 2014 Feb 12 doi: 10.1136/jnnp-2013-306981. PMID: 24521565

Recent systematic reviews

Fereshtehnejad SM, Saleh PA, Oliveira LM, Patel N, Bhowmick S, Saranza G, Kalia LV
Neurol Sci 2023 Mar;44(3):947-959. Epub 2022 Nov 28 doi: 10.1007/s10072-022-06516-8. PMID: 36441344Free PMC Article
Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793

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