TABLE 1.
Clinical characteristics of French patients carrying biallelic mutations in HINT1 compared with literature data
| Patient | 1 | 2 | 3 | 4 | 5 | 6 | 7 | Literature review a |
|---|---|---|---|---|---|---|---|---|
| Genotype | c.110G>C p.(Arg37Pro) homozygous | c.334C>A p.(His112Asn) homozygous | c.110G>C p.(Arg37Pro) homozygous | c.110G>C p.(Arg37Pro) homozygous | c.334C>A p.(His112Asn) homozygous | c.310G>C p.(Gly104Arg) homozygous | c.334C>A p.(His112Asn) homozygous | Figure 1 |
| Sex | F | M | M | M | F | M | M | F: 58% (n = 40)–M: 42% (n = 29) |
| Origin | Austrian | Portuguese | Kosovan | French | Roma | Algerian | Roma/French | Figure 2 |
| Consanguinity | No | Yes | No | No | Yes | Yes | No | Yes: 25% (n = 14) – No: 75% (n = 42) |
| Age at examination (years) | 26 | 23 | 37 | 17 | 14 | 23 | 19 | |
| Age of onset (years) | 4 | 2 | 24 | 6 | 8 | 7 | 1 | Average: 9,8 (min 2–max 30) |
| Schooling | Normal | Specialized | Normal | Normal with LSA | Specialized | Specialized | Normal | |
| Walk | Abnormal without aids | Abnormal with orthosis | Abnormal without aids | Abnormal without aids | Abnormal without aids | Abnormal without aids | Abnormal without aids | |
| Feet abnormalities | Pes planus | Pes planus, short Achille's tendons | Pes cavus | NA | Short Achille's tendons | Pes cavus, short Achille's tendons | Pes cavus | Presence: 85% (n = 29/34) |
| Scoliosis | Presence | Presence | Absence | Presence | Absence | Absence | Absence | Presence: 55% (n = 6/11) |
| DTR | Absence | Absence | Absence | Absence | Absence | Absence | Absence | |
| Clinical motor testing | Abnormal | Abnormal | Abnormal | NA | Abnormal | Abnormal | Abnormal | |
| Symptoms suggesting myotonia | Presence | Presence | Presence | Presence | Presence | Absence | Absence | 69% (n = 58/84) |
| Additional clinical features | Muscle retractions | Lordosis, irregular tremor on the finger‐nose test, overweight, hip hyperlaxity, chronic constipation | Hypersudation, Ataxia | |||||
| Median MCV (m/s) | 52 | 56.8 | NA | NA | 46.8 | 41.8 | >40 | |
| NCS | Axonal motor neuropathy | Axonal motor and sensory neuropathy | Axonal motor and sensory neuropathy | Axonal motor and sensory neuropathy | Axonal motor neuropathy | Axonal motor neuropathy | Axonal motor neuropathy |
Axonal motor neuropathy: 34% (n = 39/114) Axonal motor and sensory neuropathy: 66% (n = 75/114) |
| Neuromyotonia | Absence | Presence | Presence | Presence | Presence | Absence | Absence | 73% (n = 63/84) |
| NDD or ID | Dyslexia | ID | Absence | NDD | NDD and ID | NDD and ID | NDD and ID | n = 1/127 |
| Psychiatric disorders | Absence | Absence | Absence | Depression, TDAH | GAD and OCD | Absence | Absence | n = 3/127 |
| Brain MRI | Normal | Normal | NA | NA | Not performed | Normal | Not performed | |
| CK (norm: 0–190 IU/L) | 339 | 620 | NA | 923 | 272 | 1636 | Normal | Inscreased 67% (n = 26/39) |
Abbreviations: DTR, deep tendon reflexes; EMG, electromyography; F, female; GAD, generalized anxiety disorder; LSA, learning support assistant; ID, intellectual deficiency; M, male; MCV, motor conduction velocity; NA, not available; NDD, neurodevelopmental disorder; NCS, nerve conduction studies; OCD, obsessive–compulsive disorder.
a
Exhaustive bibliography in Appendix A.