| Gene (HGNC symbol) | Disease label / subtype | Inheritance | Key clinical hallmarks | Typical onset | Key statistics (diagnostic yield / frequency where available) | Key references with year + URL |
|---|---|---|---|---|---|---|
| **RTN2** | AR dHMN with lower-limb spasticity; distinct recessive dHMN subtype | AR | Distal upper and lower limb weakness, lower-limb spasticity, hyperreflexia, finger extensor weakness, foot deformities; axonal motor neuropathy on NCS/EMG; slowly progressive with preserved ambulation in reported cohort | First decade; table/image summary indicates **1–6 years** in many cases | 14 affected individuals from 7 consanguineous families; all ambulatory over mean disease duration **19.71 ± 13.70 years**; ages **9–50 years** in cohort (pqac-00000008, pqac-00000040) | Maroofian et al., **2024**, *Brain*, https://doi.org/10.1093/brain/awae091 (pqac-00000008, pqac-00000009, pqac-00000010) |
| **SORD** | AR dHMN / axonal CMT2 overlap; common recessive cause | AR | Motor-predominant distal lower-limb weakness/atrophy, foot drop, pes cavus, decreased/absent reflexes; mostly preserved sensory NCS though small-fiber abnormalities can occur | Childhood/adolescence; mean onset about **14 years** in Chinese series | **5/78 (6.4%)** of unresolved CMT2/dHMN in one Chinese cohort; **1% (5/485)** across hereditary neuropathy cohort; estimated up to **~10%** of previously undiagnosed dHMN/CMT2; **3.1%** in Spanish dHMN series; recurrent variant **c.757delG (p.A253Qfs*27)** (pqac-00000019, pqac-00000022, pqac-00000025, pqac-00000026) | Liu et al., **2021**, *Front Neurol*, https://doi.org/10.3389/fneur.2021.733926; Frasquet et al., **2021**, *Eur J Neurol*, https://doi.org/10.1111/ene.14700 (pqac-00000019, pqac-00000022, pqac-00000025) |
| **HINT1** | HMN with neuromyotonia; recessive motor-predominant axonal neuropathy | AR | Severe distal weakness/atrophy, axonal motor-predominant neuropathy, CK elevation; neuromyotonia/myokymia common but not universal; some muscle biopsies show chronic denervation and, in a 2023 case, rimmed vacuoles suggesting neuropathy–myopathy overlap | Usually first decade in review cohorts, but adult-onset cases also reported | Neuromyotonia in about **70–80%** of patients; **20–30%** may lack neuromyotonia; 2023 case report described novel homozygous **p.I63N (c.188T>A)** in two brothers without neuromyotonia (pqac-00000013, pqac-00000017) | Jiang et al., **2023**, *Front Neurol*, https://doi.org/10.3389/fneur.2023.1007051; Zambon et al., **2023**, *Brain*, https://doi.org/10.1093/brain/awac452 (pqac-00000014, pqac-00000017, pqac-00000018) |
| **IGHMBP2** | **HMNR1**; allelic to **CMT2S** | AR | Distal hereditary motor neuropathy / distal SMA spectrum; can overlap with SMARD1 and CMT2S; distal weakness and motor neuronopathy phenotype in aggregated tables | Often early childhood / infantile for severe spectrum; variable | Listed as **HMNR1** in the 2024 gene table; authoritative aggregated disease mapping rather than cohort frequency in retrieved evidence | Benarroch et al., **2024**, *Neuromuscular Disorders*, https://doi.org/10.1016/j.nmd.2023.12.007 (pqac-00000049, pqac-00000051) |
| **SIGMAR1** | **HMNR2**; allelic to **ALS16** | AR | Distal hereditary motor neuropathy that can mimic juvenile ALS; distal weakness/atrophy, possible pyramidal signs, slow progression, axonal motor neuropathy on EMG/NCS | Often childhood / juvenile onset in reported cases | Listed as **HMNR2** in 2024 gene table; overlap with ALS-like phenotype emphasized in case literature and review evidence | Benarroch et al., **2024**, *Neuromuscular Disorders*, https://doi.org/10.1016/j.nmd.2023.12.007; Ma et al., **2020**, *Neuromuscular Disorders*, https://doi.org/10.1016/j.nmd.2020.05.005 (pqac-00000049) |
| **PLEKHG5** | **HMNR4**; allelic to CMTRIC | AR | Distal hereditary motor neuropathy / lower motor neuron disease spectrum; aggregated source indicates established recessive subtype with overlap to recessive intermediate CMT | Variable; not specified in retrieved excerpt | Listed as **HMNR4** in 2024 gene table; no frequency statistics in retrieved excerpt | Benarroch et al., **2024**, *Neuromuscular Disorders*, https://doi.org/10.1016/j.nmd.2023.12.007 (pqac-00000049) |
| **MME** | AR late-onset dHMN (overlaps with axonal CMT2) | AR (biallelic disease; heterozygous risk/reduced penetrance also described in broader neuropathy literature) | Late-onset distal lower-limb weakness/wasting, steppage gait, distal > proximal weakness, motor-predominant axonal neuropathy with mild sensory involvement on studies despite minimal sensory symptoms | Late adult onset; reported probands onset **51** and **58** years in 2024 Chinese families | 2024 report identified novel homozygous **c.2122A>T (p.K708*)** and compound heterozygous **c.1342C>T / c.2071_2072delinsTT (p.R448* / p.A691L)**; in broader 2020 axonal neuropathy cohort, MME accounted for **34.8%** of genetically solved cases and biallelic cases had median onset **45 years** (pqac-00000043, pqac-00000046) | Zhang et al., **2024**, *BMC Med Genomics*, https://doi.org/10.1186/s12920-024-01996-3; Senderek et al., **2020**, *Neurology*, https://doi.org/10.1212/WNL.0000000000011132 (pqac-00000043, pqac-00000046) |
| **NOTCH2NLC** (GGC repeat expansion; non-classic mechanism) | Repeat-expansion–associated dHMN phenotype / lower motor neuron syndrome; not classic AR HMNR | Usually AD / repeat-expansion mechanism | dHMN phenotype in a subset, with distal weakness and intranuclear inclusions; important in genetically unsolved patients because standard exon-focused NGS may miss repeat expansions | Variable; often adult onset in reported families | In a 90-family dHMN cohort, **2 dominant families** had 5'UTR **GGC repeat expansion** in **NOTCH2NLC**; overall molecular yield **36.7% (33/90)**, rising to **46.7%** including VUS, and authors recommended STR screening in unsolved dHMN (pqac-00000035, pqac-00000037, pqac-00000038) | Wu et al., **2022**, *Ann Clin Transl Neurol*, https://doi.org/10.1002/acn3.51543; Parmar et al., **2024**, *JNNP*, https://doi.org/10.1136/jnnp-2024-333436 (pqac-00000035, pqac-00000037, pqac-00000031) |


*Table: This table summarizes the principal autosomal recessive distal hereditary motor neuropathy genes and subtypes supported by the retrieved evidence, with phenotype, onset, frequency, and key references. It also includes NOTCH2NLC as an important non-classic repeat-expansion mechanism relevant to genetically unsolved dHMN cases.*