IllnessNeuropathy, distal hereditary motor / muscle atrophies, distal spinal; differential diagnosis

NGS +

Distal hereditary motor neuropathies (dHMN) and distal spinal muscular atrophies (DSMA) are nowadays collectively referred to as Charcot-Marie-Tooth (CMT) hereditary neuropathies. In dHMN, motor symptoms are exclusively present, manifesting in the distal muscle groups. Muscle atrophy and paresis in the lower extremities are quite prominent. However, there are also forms that preferentially affect the arm or hand muscles. Clinically and genetically, there are transitions to DSMA, which by definition show neither pathological abnormalities in the peripheral nervous system nor neurogenic remodeling processes in the affected muscles on electrophysiological or histological examination. BSCL2 mutations account for a high proportion of autosomal dominant inherited forms in dHMN/DSMA and cause a wide clinical spectrum from CMT2 to dHMN to spastic paraplegia type 17. HSPB1 and HSPB8 mutations are found in 5-8% of dHMN cases. Overall, the genetic yield in dHMN/DSMA is ~40%. Therefore, a negative molecular genetic finding by no means excludes the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK1358/

https://www.awmf.org/uploads/tx_szleitlinien/022-027l_S2k_Differentialdiagnose-erworbene-hereditaere-Neuropathie-Kinder-Jugendliche_2021-07_1.pdf

• Alias: Distal hereditary motor neuropathy, DHMN
• Alias: Distal spinal muscular atrophy, DSMA
• Alias: Polyneuropathie
• Allelic: Amyotrophic lateral sclerosis 16, juvenile (SIGMAR1)
• Allelic: Amyotrophic lateral sclerosis 4, juvenile (SETX)
• Allelic: Amyotrophic lateral sclerosis 8 (VAPB)
• Allelic: Amyotrophic lateral sclerosis, susceptibility to (DCNT1)
• Allelic: Deafness, AD 4A (MYH14)
• Allelic: Myasthenic syndrome, congenital, 20, presynaptic (SLC5A7)
• Allelic: Perry syndrome [parkinsonism, depression, respiratory hypoventilation] (DCNT1)
• Allelic: Spastic paraplegia 31, AD (REEP1)
• Allelic: Usher syndrome type 3B (HARS1)
• Charcot-Marie-Tooth disease, RI C (PLEKHG5)
• Charcot-Marie-Tooth disease, axonal, type 2F (HSPB1)
• Charcot-Marie-Tooth disease, axonal, type 2L (HSPB8)
• Charcot-Marie-Tooth disease, axonal, type 2N (AARS1)
• Charcot-Marie-Tooth disease, axonal, type 2O (DYNC1H1)
• Charcot-Marie-Tooth disease, axonal, type 2S (IGHMBP2)
• Charcot-Marie-Tooth disease, axonal, type 2W (HARS1)
• Charcot-Marie-Tooth disease, type 1A (PMP22)
• Charcot-Marie-Tooth disease, type 1E (PMP22)
• Charcot-Marie-Tooth disease, type 2D (GARS1)
• Dejerine-Sottas disease (PMP22)
• Developmental + epileptic encephalopathy 29 (AARS1)
• Glucose/galactose malabsorption (SLC5A1)
• Hereditary motor + sensory neuropathy, Okinawa type (TFG)
• Hereditary motor + sensory neuropathy, type IIc (TRPV4)
• Neuromyotonia + axonal neuropathy, AR (HINT1)
• Neuronopathy, distal hereditary motor, type IIA (HSPB8)
• Neuronopathy, distal hereditary motor, type IIB (HSPB1)
• Neuronopathy, distal hereditary motor, type IIC (HSPB3)
• Neuronopathy, distal hereditary motor, type IID (FBXO38)
• Neuronopathy, distal hereditary motor, type IX (WARS)
• Neuronopathy, distal hereditary motor, type VA (GARS1)
• Neuronopathy, distal hereditary motor, type VB (REEP1)
• Neuronopathy, distal hereditary motor, type VI (IGHMBP2)
• Neuronopathy, distal hereditary motor, type VIIA (SLC5A7)
• Neuronopathy, distal hereditary motor, type VIIB (DCNT1)
• Neuronopathy, distal hereditary motor, type VIII (TRPV4)
• Neuropathy, distal hereditary motor, type VA (BSCL2)
• Neuropathy, inflammatory demyelinating (PMP22)
• Neuropathy, recurrent, with pressure palsies (PMP22)
• Peripheral neuropathy, myopathy, hoarseness, hearing loss (MYH14)
• Pontocerebellar hypoplasia, type 1A (VRK1)
• Pontocerebellar hypoplasia, type 1B (EXOSC3)
• Pontocerebellar hypoplasia, type 1C (EXOSC8)
• Pontocerebellar hypoplasia, type 2A, 4, 5 (TSEN54)
• Roussy-Levy syndrome (PMP22)
• Spastic paraplegia 57, AR (TFG)
• Spinal muscular atrophy with progressive myoclonic epilepsy (ASAH1)
• Spinal muscular atrophy, Jokela type (CHCHD10)
• Spinal muscular atrophy, XL 2, infantile (UBA1)
• Spinal muscular atrophy, distal, AR, 2 (SIGMAR1)
• Spinal muscular atrophy, distal, AR, 4 (PLEKHG5)
• Spinal muscular atrophy, distal, AR, 5 (DNAJB2)
• Spinal muscular atrophy, distal, XL 3 (ATP7A)
• Spinal muscular atrophy, late-onset, Finkel type (VAPB)
• Spinal muscular atrophy, lower extremity-predominant 1, AD (DYNC1H1)
• Spinal muscular atrophy, lower extremity-predominant, 2A + 2B, AD (BICD2)
• Spinal muscular atrophy-1, -2, -3, -4 (SMN1)
• Spinocerebellar ataxia, AR, with axonal neuropathy 2 (SETX)