IllnessSpastic paraplegia, autosomal dominant; differential diagnosis

NGS +

[Sanger]

Hereditary spastic paraplegias (HSPs) comprise a heterogeneous group of monogenic neurological diseases caused by length-dependent degeneration of the corticospinal tract and posterior cortical strands and manifests itself with bilateral spasticity of the lower extremities, hyperreflexia and plantar reactions of the extensor muscles. HSPs can occur in infancy, childhood, adolescence or adulthood. Furthermore, cognitive impairment, ataxia, dysarthria, neuropathy or seizures can be important additional symptoms in more than half of the cases. Autosomal dominantly inherited HSP occurs in about 75-80% of all HSP patients. Autosomal dominant HSP is heterogeneous, with SPG4, SPG3a and SPG31 together accounting for up to 60% of cases in this category. An inconspicuous genetic finding still does not mean a reliable exclusion of the suspected clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1509/

https://www.thelancet.com/action/showPdf?pii=S1474-4422%2819%2930235-2

• Alias: Hereditary spastic paraplegia, HSP
• Alias: Spastic paraplegia, AD
• Allelic: Amyotrophic lateral sclerosis, susceptibility to, 25 (KIF5A)
• Allelic: Charcot-Marie-Tooth disease, DI B (DNM2)
• Allelic: Charcot-Marie-Tooth disease, axonal type 2M (DNM2)
• Allelic: Congenital cataracts, hearing loss + neurodegeneration (SLC33A1)
• Allelic: Cutis laxa, AD 3 (ALDH18A1)
• Allelic: Cutis laxa, AR, type IIIA (ALDH18A1)
• Allelic: Developmental + epileptic encephalopathy 42 (CACNA1A)
• Allelic: Dyschromatosis symmetrica hereditaria (ADAR)
• Allelic: Encephalopathy, progressive, with/-out lipodystrophy (BSCL2)
• Allelic: Epilepsy, idiopathic generalized, susceptibility to, 12 (SLC2A1)
• Allelic: Episodic ataxia, type 2 (CACNA1A)
• Allelic: GLUT1 deficiency syndrome 2, childhood onset (SLC2A1)
• Allelic: Hyperphenylalaninemia, BH4-deficient, B (GCH1)
• Allelic: Lethal congenital contracture syndrome 5 (DNM2)
• Allelic: Leukodystrophy, hypomyelinating, 4 (HPSD1)
• Allelic: Leukodystrophy, hypomyelinating, 6 (TUBB4A)
• Allelic: Lipodystrophy, congenital generalized, type 2 (BSCL2)
• Allelic: Lopes-Maciel-Rodan syndrome (HTT)
• Allelic: Migraine, familial hemiplegic, 1 (CACNA1A)
• Allelic: Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia (CACNA1A_CAG)
• Allelic: Myoclonus, intractable, neonatal (KIF5A)
• Allelic: NESCAV syndrome (KIF1A)
• Allelic: Neuronopathy, distal hereditary motor, type VB (REEP1)
• Allelic: Neuropathy, distal hereditary motor, type VA (BSCL2)
• Allelic: Neuropathy, hereditary sensory, type ID (ATL1)
• Allelic: Neuropathy, hereditary sensory, type IIC (KIF1A)
• Allelic: Optic atrophy 12 (AFG3L2)
• Allelic: Pontocereb. hypoplasia, hypotonia, respiratory insufficiency s., neonatal lethal (ATAD3A)
• Allelic: Ritscher-Schinzel syndrome 1 (WASHC5)
• Allelic: Spastic ataxia 5, AR (AFG3L2)
• Allelic: Spastic paraplegia 30, AR (KIF1A)
• Allelic: Spastic paraplegia 9B, AR (ALDH18A1)
• Allelic: Stomatin-deficient cryohydrocytosis with neurologic defects (SLC2A1)
• Allelic: Ventriculomegaly + arthrogryposis (KIDINS220)
• Aicardi-Goutieres syndrome 6 (ADAR)
• Centronuclear myopathy 1 (DNM2)
• Dystonia 4, torsion, AD (TUBB4A)
• Dystonia 9 (SLC2A1)
• Dystonia, DOPA-responsive, with/-out hyperphenylalaninemia (GCH1)
• Encephalopathy, progressive, with/-out lipodystrophy (BSCL2)
• GLUT1 deficiency syndrome 1, infantile onset, severe (SLC2A1)
• Harel-Yoon syndrome (ATAD3A)
• Huntington disease (HTT_CAG)
• Machado-Joseph disease (ATXN3_CAG)
• Silver spastic paraplegia syndrome (BSCL2)
• Spastic paraplegia 10, AD (KIF5A)
• Spastic paraplegia 12, AD (RTN2)
• Spastic paraplegia 13, AD (HSPD1)
• Spastic paraplegia 18, AD + AR (ERLIN2)
• Spastic paraplegia 30, AD (KIF1A)
• Spastic paraplegia 31, AD (REEP1)
• Spastic paraplegia 33, AD (ZFYVE27)
• Spastic paraplegia 3A, AD (ATL1)
• Spastic paraplegia 4, AD (SPAST)
• Spastic paraplegia 42, AD (SLC33A1)
• Spastic paraplegia 6, AD (NIPA1)
• Spastic paraplegia 7, AD + AR (SPG7)
• Spastic paraplegia 72, [AD +] AR (REEP2)
• Spastic paraplegia 73, AD (CPT1C)
• Spastic paraplegia 8, AD (WASHC5)
• Spastic paraplegia 80, AD (UBAP1)
• Spastic paraplegia 9A, AD (ALDH18A1)
• Spastic paraplegia, intellectual disability, nystagmus + obesity (KIDINS220)
• Spinal muscular atrophy, lower extremity-predominant, 2A + 2B, AD (BICD2)
• Spinocerebellar ataxia 1 (ATXN1_CAG)
• Spinocerebellar ataxia 10 (ATXN10_ATTCT)
• Spinocerebellar ataxia 12 PPP2R2B
• Spinocerebellar ataxia 17 (TBP_CAG)
• Spinocerebellar ataxia 2 (ATXN2_CAG)
• Spinocerebellar ataxia 28 (AFG3L2)
• Spinocerebellar ataxia 36 (NOP56_GGCCTG)
• Spinocerebellar ataxia 6 (CACNA1A_CAG)
• Spinocerebellar ataxia 7 (ATXN7_CAG)