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Hereditary spastic paraplegia 54(SPG54)

MedGen UID:
761341
Concept ID:
C3539495
Disease or Syndrome
Synonym: Spastic paraplegia 54, autosomal recessive
SNOMED CT: Autosomal recessive spastic paraplegia type 54 (723824005)
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).
 
Gene (location): DDHD2 (8p11.23)
 
Monarch Initiative: MONDO:0014018
OMIM®: 615033
Orphanet: ORPHA320380

Definition

Spastic paraplegia-54 (SPG54) is a complicated form of spastic paraplegia, a neurodegenerative disorder affecting fibers of the corticospinal tract. Affected individuals have delayed psychomotor development, intellectual disability, and early-onset spasticity of the lower limbs. Brain MRI shows a thin corpus callosum and periventricular white matter lesions. Brain magnetic resonance spectroscopy shows an abnormal lipid peak (summary by Schuurs-Hoeijmakers et al., 2012). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive spastic paraplegia, see 270800. [from OMIM]

Clinical features

From HPO
Bowel incontinence
MedGen UID:
41977
Concept ID:
C0015732
Disease or Syndrome
Involuntary fecal soiling in adults and children who have usually already been toilet trained.
Urinary incontinence
MedGen UID:
22579
Concept ID:
C0042024
Finding
Loss of the ability to control the urinary bladder leading to involuntary urination.
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.
Distal lower limb muscle weakness
MedGen UID:
324514
Concept ID:
C1836450
Finding
Reduced strength of the distal musculature of the legs.
Distal upper limb muscle weakness
MedGen UID:
461970
Concept ID:
C3150620
Finding
Reduced strength of the distal musculature of the arms.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Constipation
MedGen UID:
1101
Concept ID:
C0009806
Sign or Symptom
Infrequent or difficult evacuation of feces.
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.
Syringomyelia
MedGen UID:
21449
Concept ID:
C0039144
Disease or Syndrome
Dilated, glial-lined cavity in spinal cord. This cavity does not communicate with the central canal, and usually is between the dorsal columns unilaterally or bilaterally along the side of the cord.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Upper limb spasticity
MedGen UID:
220882
Concept ID:
C1273957
Finding
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
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.
Rigidity
MedGen UID:
7752
Concept ID:
C0026837
Sign or Symptom
Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Telecanthus
MedGen UID:
140836
Concept ID:
C0423113
Finding
Distance between the inner canthi more than two standard deviations above the mean (objective); or, apparently increased distance between the inner canthi.
Hypomimic face
MedGen UID:
208827
Concept ID:
C0813217
Finding
A reduced degree of motion of the muscles beneath the skin of the face, often associated with reduced facial crease formation.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Optic nerve hypoplasia
MedGen UID:
137901
Concept ID:
C0338502
Disease or Syndrome
Underdevelopment of the optic nerve.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary spastic paraplegia 54
Follow this link to review classifications for Hereditary spastic paraplegia 54 in Orphanet.

Recent clinical studies

Etiology

Jia F, Wang X, Fu Y, Zhao SM, Lu B, Wang C
Cell Death Differ 2024 Mar;31(3):348-359. Epub 2024 Feb 8 doi: 10.1038/s41418-024-01261-1. PMID: 38332048Free PMC Article
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
Yang JO, Yoon JY, Sung DH, Yun S, Lee JJ, Jun SY, Halder D, Jeon SJ, Woo EJ, Seok JM, Cho JW, Jang JH, Choi JK, Kim BJ, Kim NS
Genomics 2021 Nov;113(6):4136-4148. Epub 2021 Oct 27 doi: 10.1016/j.ygeno.2021.10.014. PMID: 34715294
Ebrahimi-Fakhari D, Teinert J, Behne R, Wimmer M, D'Amore A, Eberhardt K, Brechmann B, Ziegler M, Jensen DM, Nagabhyrava P, Geisel G, Carmody E, Shamshad U, Dies KA, Yuskaitis CJ, Salussolia CL, Ebrahimi-Fakhari D, Pearson TS, Saffari A, Ziegler A, Kölker S, Volkmann J, Wiesener A, Bearden DR, Lakhani S, Segal D, Udwadia-Hegde A, Martinuzzi A, Hirst J, Perlman S, Takiyama Y, Xiromerisiou G, Vill K, Walker WO, Shukla A, Dubey Gupta R, Dahl N, Aksoy A, Verhelst H, Delgado MR, Kremlikova Pourova R, Sadek AA, Elkhateeb NM, Blumkin L, Brea-Fernández AJ, Dacruz-Álvarez D, Smol T, Ghoumid J, Miguel D, Heine C, Schlump JU, Langen H, Baets J, Bulk S, Darvish H, Bakhtiari S, Kruer MC, Lim-Melia E, Aydinli N, Alanay Y, El-Rashidy O, Nampoothiri S, Patel C, Beetz C, Bauer P, Yoon G, Guillot M, Miller SP, Bourinaris T, Houlden H, Robelin L, Anheim M, Alamri AS, Mahmoud AAH, Inaloo S, Habibzadeh P, Faghihi MA, Jansen AC, Brock S, Roubertie A, Darras BT, Agrawal PB, Santorelli FM, Gleeson J, Zaki MS, Sheikh SI, Bennett JT, Sahin M
Brain 2020 Oct 1;143(10):2929-2944. doi: 10.1093/brain/awz307. PMID: 32979048Free PMC Article
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320

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
Yang JO, Yoon JY, Sung DH, Yun S, Lee JJ, Jun SY, Halder D, Jeon SJ, Woo EJ, Seok JM, Cho JW, Jang JH, Choi JK, Kim BJ, Kim NS
Genomics 2021 Nov;113(6):4136-4148. Epub 2021 Oct 27 doi: 10.1016/j.ygeno.2021.10.014. PMID: 34715294
Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Ebrahimi-Fakhari D, Teinert J, Behne R, Wimmer M, D'Amore A, Eberhardt K, Brechmann B, Ziegler M, Jensen DM, Nagabhyrava P, Geisel G, Carmody E, Shamshad U, Dies KA, Yuskaitis CJ, Salussolia CL, Ebrahimi-Fakhari D, Pearson TS, Saffari A, Ziegler A, Kölker S, Volkmann J, Wiesener A, Bearden DR, Lakhani S, Segal D, Udwadia-Hegde A, Martinuzzi A, Hirst J, Perlman S, Takiyama Y, Xiromerisiou G, Vill K, Walker WO, Shukla A, Dubey Gupta R, Dahl N, Aksoy A, Verhelst H, Delgado MR, Kremlikova Pourova R, Sadek AA, Elkhateeb NM, Blumkin L, Brea-Fernández AJ, Dacruz-Álvarez D, Smol T, Ghoumid J, Miguel D, Heine C, Schlump JU, Langen H, Baets J, Bulk S, Darvish H, Bakhtiari S, Kruer MC, Lim-Melia E, Aydinli N, Alanay Y, El-Rashidy O, Nampoothiri S, Patel C, Beetz C, Bauer P, Yoon G, Guillot M, Miller SP, Bourinaris T, Houlden H, Robelin L, Anheim M, Alamri AS, Mahmoud AAH, Inaloo S, Habibzadeh P, Faghihi MA, Jansen AC, Brock S, Roubertie A, Darras BT, Agrawal PB, Santorelli FM, Gleeson J, Zaki MS, Sheikh SI, Bennett JT, Sahin M
Brain 2020 Oct 1;143(10):2929-2944. doi: 10.1093/brain/awz307. PMID: 32979048Free PMC Article
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320

Therapy

Bastani PB, Kordjazi M, Oveisgharan S, Abdi S
J Clin Neurophysiol 2023 Feb 1;40(2):173-179. Epub 2021 Nov 23 doi: 10.1097/WNP.0000000000000874. PMID: 34817445

Prognosis

Yang JO, Yoon JY, Sung DH, Yun S, Lee JJ, Jun SY, Halder D, Jeon SJ, Woo EJ, Seok JM, Cho JW, Jang JH, Choi JK, Kim BJ, Kim NS
Genomics 2021 Nov;113(6):4136-4148. Epub 2021 Oct 27 doi: 10.1016/j.ygeno.2021.10.014. PMID: 34715294
Wagley Y, Choi JH, Wickramanayake DD, Choi GY, Kim CK, Kim TH, Oh JW
Monoclon Antib Immunodiagn Immunother 2013 Aug;32(4):277-82. doi: 10.1089/mab.2013.0015. PMID: 23909422Free PMC Article
Feng Y, Ke X, Zhai M, Xin Q, Gong Y, Liu Q
Singapore Med J 2013 May;54(5):251-4. doi: 10.11622/smedj.2013102. PMID: 23716148
Alvarez V, Sánchez-Ferrero E, Beetz C, Díaz M, Alonso B, Corao AI, Gámez J, Esteban J, Gonzalo JF, Pascual-Pascual SI, López de Munain A, Moris G, Ribacoba R, Márquez C, Rosell J, Marín R, García-Barcina MJ, Del Castillo E, Benito C, Coto E; Group for the Study of the Genetics of Spastic Paraplegia
BMC Neurol 2010 Oct 8;10:89. doi: 10.1186/1471-2377-10-89. PMID: 20932283Free PMC Article
Mostacciuolo ML, Rampoldi L, Righetti E, Vazza G, Schiavon F, Angelini C
Neuromuscul Disord 2000 Oct;10(7):497-502. doi: 10.1016/s0960-8966(00)00128-0. PMID: 10996781

Clinical prediction guides

Jia F, Wang X, Fu Y, Zhao SM, Lu B, Wang C
Cell Death Differ 2024 Mar;31(3):348-359. Epub 2024 Feb 8 doi: 10.1038/s41418-024-01261-1. PMID: 38332048Free PMC Article
Yang JO, Yoon JY, Sung DH, Yun S, Lee JJ, Jun SY, Halder D, Jeon SJ, Woo EJ, Seok JM, Cho JW, Jang JH, Choi JK, Kim BJ, Kim NS
Genomics 2021 Nov;113(6):4136-4148. Epub 2021 Oct 27 doi: 10.1016/j.ygeno.2021.10.014. PMID: 34715294
Du J
J Clin Neurosci 2021 Mar;85:67-71. Epub 2021 Jan 15 doi: 10.1016/j.jocn.2020.11.036. PMID: 33581793
Luo Y, Chen C, Zhan Z, Wang Y, Du J, Hu Z, Liao X, Zhao G, Wang J, Yan X, Jiang H, Pan Q, Xia K, Tang B, Shen L
Neurodegener Dis 2014;14(4):176-83. Epub 2014 Oct 22 doi: 10.1159/000365513. PMID: 25341883
Vahter L, Braschinsky M, Haldre S, Gross-Paju K
Clin Rehabil 2009 Sep;23(9):857-61. Epub 2009 Jun 26 doi: 10.1177/0269215509337186. PMID: 19561033

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
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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