IllnessDystonia-Parkinson syndrome, diufferential diagnosis

NGS +

[Sanger]

X-linked dystonia-parkinsonism (XLDP) is the prime example for this group of diseases, the other pertinent genes are mostly subsumed under dystonias, their mutated genes are mentioned below. XLDP is a movement disorder exclusively observed in people of Filipino descent. Parkinsonism is usually the first sign of the disease with tremors, bradykinesia, rigidity, postural instability and a shuffling gait. Later in life, many affecteds individuals also develop dystonia typically starting in areas of the eyes, jaw or neck which later spread with disabling spasms. Generalized dystonia disturbs speaking, swallowing, coordination and walking. The symptoms of dystonia-parkinsonism (DP) vary widely. In severe cases the affecteds become dependent on others for care within a few years, and they may die prematurely from breathing difficulties, infections or other complications. TAF1 mutations cause XLDP. The gene is part of the complex TAF1/DYT3 multiple transcript system. This condition is inherited in an X-linked pattern. Genes to be considered In the differential diagnosis of DP include ATP1A3, GCH1, KCTD17, PRKRA, SPR, TH, C19orf12, PANK2, SLC30A10, SLC39A14, SLC6A3, TUBB4A, WDR45 and others. These DP disorders are inherited rarely in an XL pattern, more often in autosomal recessive or dominant patterns. Since the yield via molecular genetics reaches barely 90%, a negative DNA test result does not exclude the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK1489/

https://www.ncbi.nlm.nih.gov/books/NBK1155/

• Alias: Adult-onset dystonia-parkinsonism, included
• Alias: Infantile dystonia-parkinsonism, included
• Alias: Rapid-onset dystonia-parkinsonism, included
• Allelic: Autism susceptibility, XL 3 (MECP2)
• Allelic: Developmental and epileptic encephalopathy 53 (SYNJ1)
• Allelic: Dystonia 3, torsion, XL (TAF1)
• Allelic: Dystonia musculorum deformans (TAF1)
• Allelic: Dystonia-parkinsonism, XL (TAF1)
• Allelic: Encephalopathy, neonatal severe (MECP2)
• Allelic: Hyperostosis cranalis interna (SLC39A14)
• Allelic: Lopes-Maciel-Rodan syndrome (HTT)
• Allelic: Lubag syndrome (TAF1)
• Allelic: Rett syndrome (MECP2)
• Allelic: Torsion dystonia-parkinsonism, Filipino type
• Allelic: XL dystonia-parkinsonism syndrome (TAF1)
• Allelic: XL torsion dystonia-parkinsonism syndrome (TAF1)
• Alternating hemiplegia of childhood (ATP1A3)
• CAPOS syndrome (ATP1A3)
• Choreoacanthocytosis (VPS13A)
• Dystonia 11, myoclonic (SGCE)
• Dystonia 12 (ATP1A3)
• Dystonia 16 (PRKRA)
• Dystonia 26, myoclonic (KCTD7)
• Dystonia 4, torsion, AD (TUBB4A)
• Dystonia, DOPA-responsive, with or without hyperphenylalaninemia (GCH1)
• Dystonia, dopa-responsive, due to sepiapterin reductase deficiency (SPR)
• Dystonia-Parkinsonism, XL (TAF1)
• Early-onset dystonia parkinsonism, included
• Huntington disease (HTT)
• Hypermanganesemia with dystonia 1 (SLC30A10)
• Hypermanganesemia with dystonia 2 (SLC39A14)
• Hyperphenylalaninemia, BH4-deficient, B (GCH1)
• Hypoprebetalipoproteinemia, acanthocytosis, retinitis pigm. + pallidal degeneration/HARP s. (PANK2)
• Intellectual developmental disorder, XL syndromic, Lubs type (MECP2)
• Intellectual developmental disorder, XL, syndromic 13 (MECP2)
• Kufor-Rakeb syndrome (ATP13A2)
• Leukodystrophy, hypomyelinating, 6 (TUBB4A)
• McLeod syndrome with/-out chronic granulomatous disease (XK)
• Mental retardation, X-linked, syndromic 3 (TAF1)
• Neurodegeneration with brain iron accumulation 1 (PANK2)
• Neurodegeneration with brain iron accumulation 4 (C19orf12)
• Neurodegeneration with brain iron accumulation 5 (WDR45)
• Nicotine dependence, protection against (SLC6A3)
• PLA2G6-related dystonia-parkinsonism (PLA2G6)
• Parkinson disease 15, AR (FBXO7)
• Parkinson disease 20, early-onset (SYNJ1)
• Parkinson disease, juvenile, type 2 (PRKN)
• Parkinsonism-dystonia, infantile, 1 (SLC6A3)
• Rett syndrome, atypical (MECP2)
• Rett syndrome, preserved speech variant (MECP2)
• Segawa syndrome, recessive (TH)
• Spastic paraplegia 43, AR (C19orf12)
• Spastic paraplegia 78, AR (ATP13A2)