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Spastic paraplegia 84, autosomal recessive(SPG84)

MedGen UID:
1794235
Concept ID:
C5562025
Disease or Syndrome
Synonym: SPG84
 
Gene (location): PI4KA (22q11.21)
 
Monarch Initiative: MONDO:0030482
OMIM®: 619621

Disease characteristics

Excerpted from the GeneReview: PI4KA-Related Disorder
PI4KA-related disorder is a clinically variable disorder characterized primarily by neurologic dysfunction (limb spasticity, developmental delay, intellectual disability, seizures, ataxia, nystagmus), gastrointestinal manifestations (multiple intestinal atresia, inflammatory bowel disease), and combined immunodeficiency (leukopenia, variable immunoglobulin defects). Age of onset is typically antenatal or in early childhood; individuals can present with any combination of these features. Rare individuals present with later-onset hereditary spastic paraplegia. Brain MRI findings can include hypomyelinating leukodystrophy, cerebellar hypoplasia/atrophy, thin or dysplastic corpus callosum, and/or perisylvian polymicrogyria. [from GeneReviews]
Authors:
Emma L Baple  |  Claire Salter  |  Holm Uhlig, et. al.   view full author information

Additional description

From OMIM
Autosomal recessive spastic paraplegia-84 (SPG84) is characterized by onset of slowly progressive walking difficulties due to lower limb weakness, stiffness, and spasticity in the first 2 decades of life. Additional features may include nystagmus, urinary urgency, joint contractures, and possible learning disabilities (summary by Verdura et al., 2021). For a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see SPG5A (270800).  http://www.omim.org/entry/619621

Clinical features

From HPO
Urinary urgency
MedGen UID:
39315
Concept ID:
C0085606
Finding
Urge incontinence is the strong, sudden need to urinate.
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.
Knee flexion contracture
MedGen UID:
98042
Concept ID:
C0409355
Finding
A type of knee joint contracture in which the knee is in a fixed bent (flexed) configuration such that it cannot be straightened actively or passively.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
Lower limb muscle weakness
MedGen UID:
324478
Concept ID:
C1836296
Finding
Weakness of the muscles of the legs.
Ankle flexion contracture
MedGen UID:
332440
Concept ID:
C1837407
Anatomical Abnormality
Crohn disease
MedGen UID:
3664
Concept ID:
C0010346
Disease or Syndrome
A chronic granulomatous inflammatory disease of the intestines that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms. It primarily causes abdominal pain, diarrhea which may be bloody, vomiting, or weight loss, but may also cause complications outside of the gastrointestinal tract such as skin rashes, arthritis, inflammation of the eye, tiredness, and lack of concentration. Crohn's disease is thought to be an autoimmune disease, in which the body's immune system attacks the gastrointestinal tract, causing inflammation.
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.
Arachnoid cyst
MedGen UID:
86860
Concept ID:
C0078981
Disease or Syndrome
An extra-parenchymal and intra-arachnoidal collection of fluid with a composition similar to that of cerebrospinal fluid.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Hoffmann sign
MedGen UID:
78828
Concept ID:
C0277839
Sign or Symptom
A Hoffmann test is performed by flicking the fingernail of the long finger, from dorsal to volar, on each hand while the hand was supported by the examiner's hand. The test was done with the neck in the neutral position and then with the neck maximally forward flexed. Any flexion of the ipsilateral thumb and/or index finger was interpreted as a positive test.
Cognitive impairment
MedGen UID:
90932
Concept ID:
C0338656
Mental or Behavioral Dysfunction
Abnormal cognition is characterized by deficits in thinking, reasoning, or remembering.
Tip-toe gait
MedGen UID:
98104
Concept ID:
C0427144
Finding
An abnormal gait pattern characterized by the failure of the heel to contact the floor at the onset of stance during gait.
Gait disturbance
MedGen UID:
107895
Concept ID:
C0575081
Finding
The term gait disturbance can refer to any disruption of the ability to walk.
Cervical spinal cord atrophy
MedGen UID:
451068
Concept ID:
C0742191
Disease or Syndrome
Atrophy of the cervical segment of the spinal cord.
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.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Hip contracture
MedGen UID:
140815
Concept ID:
C0409354
Acquired Abnormality
Lack of full passive range of motion (restrictions in flexion, extension, or other movements) of the hip joint resulting from structural changes of non-bony tissues, such as muscles, tendons, ligaments, joint capsules and/or skin.
Frequent falls
MedGen UID:
163408
Concept ID:
C0850703
Finding
Leg muscle stiffness
MedGen UID:
870176
Concept ID:
C4024610
Sign or Symptom
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.

Recent clinical studies

Etiology

Kilic MA, Yildiz EP, Deniz A, Coskun O, Kurekci F, Avci R, Genc HM, Yesil G, Akbas S, Yesilyurt A, Kara B
Pediatr Neurol 2024 Mar;152:189-195. Epub 2024 Jan 6 doi: 10.1016/j.pediatrneurol.2024.01.005. PMID: 38301322
Servelhere KR, Rezende TJR, de Lima FD, de Brito MR, de França Nunes RF, Casseb RF, Pedroso JL, Barsottini OGP, Cendes F, França MC Jr
Mov Disord 2021 Jul;36(7):1644-1653. Epub 2021 Feb 11 doi: 10.1002/mds.28519. PMID: 33576112
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320
Olmez A, Uyanik G, Ozgül RK, Gross C, Cirak S, Elibol B, Anlar B, Winner B, Hehr U, Topaloglu H, Winkler J
Neuropediatrics 2006 Apr;37(2):59-66. doi: 10.1055/s-2006-923982. PMID: 16773502

Diagnosis

Beichert L, Ilg W, Kessler C, Traschütz A, Reich S, Santorelli FM, Başak AN, Gagnon C; PROSPAX Consortium, Schüle R, Synofzik M
Mov Disord 2024 Sep;39(9):1544-1555. Epub 2024 Jun 7 doi: 10.1002/mds.29876. PMID: 38847438
Kilic MA, Yildiz EP, Deniz A, Coskun O, Kurekci F, Avci R, Genc HM, Yesil G, Akbas S, Yesilyurt A, Kara B
Pediatr Neurol 2024 Mar;152:189-195. Epub 2024 Jan 6 doi: 10.1016/j.pediatrneurol.2024.01.005. PMID: 38301322
Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320
Olmez A, Uyanik G, Ozgül RK, Gross C, Cirak S, Elibol B, Anlar B, Winner B, Hehr U, Topaloglu H, Winkler J
Neuropediatrics 2006 Apr;37(2):59-66. doi: 10.1055/s-2006-923982. PMID: 16773502

Therapy

Zhang J, Huang Y, Hu Y, Bai B
Int J Dev Neurosci 2024 Jun;84(4):305-313. Epub 2024 Apr 2 doi: 10.1002/jdn.10328. PMID: 38566307

Prognosis

Rudenskaya GE, Kadnikova VA, Ryzhkova OP, Bessonova LA, Dadali EL, Guseva DS, Markova TV, Khmelkova DN, Polyakov AV
BMC Neurol 2020 Aug 3;20(1):290. doi: 10.1186/s12883-020-01872-4. PMID: 32746806Free PMC Article
Faber I, Martinez ARM, de Rezende TJR, Martins CR Jr, Martins MP, Lourenço CM, Marques W Jr, Montecchiani C, Orlacchio A, Pedroso JL, Barsottini OGP, Lopes-Cendes Í, França MC Jr
Neuroimage Clin 2018;19:848-857. Epub 2018 Jun 9 doi: 10.1016/j.nicl.2018.05.031. PMID: 29946510Free PMC Article
Olmez A, Uyanik G, Ozgül RK, Gross C, Cirak S, Elibol B, Anlar B, Winner B, Hehr U, Topaloglu H, Winkler J
Neuropediatrics 2006 Apr;37(2):59-66. doi: 10.1055/s-2006-923982. PMID: 16773502
Sommerfelt K, Kyllerman M, Sanner G
Acta Neurol Scand 1991 Aug;84(2):157-60. doi: 10.1111/j.1600-0404.1991.tb04925.x. PMID: 1950452

Clinical prediction guides

Beichert L, Ilg W, Kessler C, Traschütz A, Reich S, Santorelli FM, Başak AN, Gagnon C; PROSPAX Consortium, Schüle R, Synofzik M
Mov Disord 2024 Sep;39(9):1544-1555. Epub 2024 Jun 7 doi: 10.1002/mds.29876. PMID: 38847438
Kilic MA, Yildiz EP, Deniz A, Coskun O, Kurekci F, Avci R, Genc HM, Yesil G, Akbas S, Yesilyurt A, Kara B
Pediatr Neurol 2024 Mar;152:189-195. Epub 2024 Jan 6 doi: 10.1016/j.pediatrneurol.2024.01.005. PMID: 38301322
Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Olmez A, Uyanik G, Ozgül RK, Gross C, Cirak S, Elibol B, Anlar B, Winner B, Hehr U, Topaloglu H, Winkler J
Neuropediatrics 2006 Apr;37(2):59-66. doi: 10.1055/s-2006-923982. PMID: 16773502
Wilkinson PA, Crosby AH, Turner C, Patel H, Wood NW, Schapira AH, Warner TT
Neurology 2003 Jul 22;61(2):235-8. doi: 10.1212/01.wnl.0000069920.42968.8d. PMID: 12874406

Recent systematic reviews

Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320

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