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Spastic paraplegia 88, autosomal dominant(SPG88)

MedGen UID:
1824020
Concept ID:
C5774247
Disease or Syndrome
Synonyms: SPASTIC PARAPLEGIA 88, AUTOSOMAL DOMINANT; SPG88
 
Gene (location): KPNA3 (13q14.2)
 
Monarch Initiative: MONDO:0859309
OMIM®: 620106

Definition

Autosomal dominant spastic paraplegia-88 (SPG88) is characterized by onset of symptoms in the first year of life. Affected individuals show delayed motor development with walking difficulties due to spasticity of the lower limbs. The disorder is slowly progressive, but variable in severity; some patients are unable to ambulate independently. Most patients have a pure form of the disorder, although rare patients have been reported to have additional features, including peripheral neuropathy, speech delay, ADHD, and nonspecific brain imaging abnormalities (Schob et al., 2021, Estiar et al., 2022, De Winter et al., 2022). For a general phenotypic description and a discussion of genetic heterogeneity of autosomal dominant spastic paraplegia, see SPG3A (182600). [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.
Lower limb muscle weakness
MedGen UID:
324478
Concept ID:
C1836296
Finding
Weakness of the muscles of the legs.
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.
Unsteady gait
MedGen UID:
68544
Concept ID:
C0231686
Finding
A shaky or wobbly manner of walking.
Sensory ataxia
MedGen UID:
66020
Concept ID:
C0240991
Sign or Symptom
Incoordination of movement caused by a deficit in the sensory nervous system. Sensory ataxia can be distinguished from cerebellar ataxia by asking the patient to close his or her eyes. Persons with cerebellar ataxia show only a minimal worsening of symptoms, whereas persons with sensory ataxia show a marked worsening of symptoms.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
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.
Attention deficit hyperactivity disorder
MedGen UID:
220387
Concept ID:
C1263846
Mental or Behavioral Dysfunction
Attention-deficit/hyperactivity disorder (ADHD) is a behavioral disorder that typically begins in childhood and is characterized by a short attention span (inattention), an inability to be calm and stay still (hyperactivity), and poor impulse control (impulsivity). Some people with ADHD have problems with only inattention or with hyperactivity and impulsivity, but most have problems related to all three features.\n\nIn people with ADHD, the characteristic behaviors are frequent and severe enough to interfere with the activities of daily living such as school, work, and relationships with others. Because of an inability to stay focused on tasks, people with inattention may be easily distracted, forgetful, avoid tasks that require sustained attention, have difficulty organizing tasks, or frequently lose items.\n\nIn most affected individuals, ADHD continues throughout life, but in about one-third of individuals, signs and symptoms of ADHD go away by adulthood.\n\nHyperactivity is usually shown by frequent movement. Individuals with this feature often fidget or tap their foot when seated, leave their seat when it is inappropriate to do so (such as in the classroom), or talk a lot and interrupt others.\n\nImpulsivity can result in hasty actions without thought for the consequences. Individuals with poor impulse control may have difficulty waiting for their turn, deferring to others, or considering their actions before acting.\n\nMore than two-thirds of all individuals with ADHD have additional conditions, including insomnia, mood or anxiety disorders, learning disorders, or substance use disorders. Affected individuals may also have autism spectrum disorder, which is characterized by impaired communication and social interaction, or Tourette syndrome, which is a disorder characterized by repetitive and involuntary movements or noises called tics.
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
Lower limb hyperreflexia
MedGen UID:
322973
Concept ID:
C1836696
Finding
Hypoplasia of the brainstem
MedGen UID:
334226
Concept ID:
C1842688
Finding
Underdevelopment of the brainstem.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Motor axonal neuropathy
MedGen UID:
413108
Concept ID:
C2749625
Disease or Syndrome
Progressive impairment of function of motor axons with muscle weakness, atrophy, and cramps. The deficits are length-dependent, meaning that muscles innervated by the longest nerves are affected first, so that for instance the arms are affected at a later age than the onset of deficits involving the lower leg.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Agenesis of cerebellar vermis
MedGen UID:
1768774
Concept ID:
C5437781
Congenital Abnormality
Congenital absence of the vermis of cerebellum.
Thin corpus callosum
MedGen UID:
1785336
Concept ID:
C5441562
Anatomical Abnormality
An abnormally thin corpus callous, due to atrophy, hypoplasia or agenesis. This term is intended to be used in situations where it is not known if thinning of the corpus callosum (for instance, as visualized by magnetic resonance tomography) is due to abnormal development (e.g. a leukodystrophy) or atrophy following normal development (e.g. neurodegeneration).
Muscle stiffness
MedGen UID:
113151
Concept ID:
C0221170
Sign or Symptom
A condition in which muscles cannot be moved quickly without accompanying pain or spasm.

Recent clinical studies

Etiology

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
Wang J, Hou Y, Qi L, Zhai S, Zheng L, Han L, Guo Y, Zhang B, Miao P, Lou Y, Xu X, Wang Y, Ren Y, Cao Z, Feng J
Neurogenetics 2020 Jul;21(3):169-177. Epub 2020 Mar 28 doi: 10.1007/s10048-020-00608-3. PMID: 32222895
Zhao GH, Hu ZM, Shen L, Jiang H, Ren ZJ, Liu XM, Xia K, Guo P, Pan Q, Tang BS
Chin Med J (Engl) 2008 Mar 5;121(5):430-4. PMID: 18364116

Diagnosis

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

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
Crimella C, Baschirotto C, Arnoldi A, Tonelli A, Tenderini E, Airoldi G, Martinuzzi A, Trabacca A, Losito L, Scarlato M, Benedetti S, Scarpini E, Spinicci G, Bresolin N, Bassi MT
Clin Genet 2012 Aug;82(2):157-64. Epub 2011 Jun 21 doi: 10.1111/j.1399-0004.2011.01717.x. PMID: 21623771

Clinical prediction guides

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
Crimella C, Baschirotto C, Arnoldi A, Tonelli A, Tenderini E, Airoldi G, Martinuzzi A, Trabacca A, Losito L, Scarlato M, Benedetti S, Scarpini E, Spinicci G, Bresolin N, Bassi MT
Clin Genet 2012 Aug;82(2):157-64. Epub 2011 Jun 21 doi: 10.1111/j.1399-0004.2011.01717.x. PMID: 21623771
Zhao GH, Hu ZM, Shen L, Jiang H, Ren ZJ, Liu XM, Xia K, Guo P, Pan Q, Tang BS
Chin Med J (Engl) 2008 Mar 5;121(5):430-4. PMID: 18364116

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