Table 1 – Phenotypic expansion of KIF1A clinical manifestation.
Molecular diagnosis and phenotypic information is presented for reach patient. Phenotypes are further categorized into seven high-level categories: head and neck, central nervous system, peripheral nervous system, musculoskeletal, urinary system, gastrointestinal system, and skin/integument. Phenotypes are indicated as either positive, negative, or not-phenotyped (or reported) for each patient. For research-consented cases, individual-level phenotypic information is presented. For the four other clinical cases, phenotypic information is presented in aggregate. The summary column indicates how many patients were positive for a given phenotype. All genomic positions are based on NC_000002.11, and amino acid changes are predicted from transcript NM_004321.6.
| RESEARCH OR CLINICAL | RESEARCH | RESEARCH | RESEARCH | RESEARCH | RESEARCH | RESEARCH | CLINICAL | CLINICAL | CLINICAL | CLINICAL | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Sample ID | PERU1 | PERU2 | BG1 | BAB11796 | BG2 (Lee et al. patient 6) | BG3 (Lee et al. patient 8) | BG4 | BG5 | BG6 | BG7 | |
| MOLECULAR | |||||||||||
| Chromosome | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | |
| Genomic Position | 241722506 | 241722506 | 241727535 | 241727527 | 241724483 | 241723197 | 241737132 | 241737132 | 241724480 | 241715279 | |
| Genomic Variant | CTTG>C | CTTG>C | G>A | C>T | T>G | C>T | C>T | C>A | G>A | C>T | |
| Amino acid change | p.Asn272del | p.Asn272del | p.Thr99Met | p.Gly102Ser | p.Ser215Arg | p.Glu253Lys | p.Arg13His | p.Arg13Leu | p.Arg216Cys | p.Arg316Gln | |
| Zygosity | Heterozygous | Heterozygous | Heterozygous | Heterozygous | Heterozygous | Heterozygous | Heterozygous | Heterozygous | Heterozygous | Heterozygous | |
| Inheritance | Parental germline mosaic | Parental germline mosaic | de novo | de novo | de novo | de novo | de novo | de novo | de novo | de novo | |
| Sex | Male | Female | Male | Male | Male | Female | Female | Female | Female | Female | |
| Age of symptoms onset | 6 months | 6 months | 6 months | 6 months | Unknown | Unknown | Unknown | Unknown | Unknown | Unknown | |
| Age at most recent phenotyping | 15 yrs | 5 yrs | 9 yrs | 14 yrs | 2 yrs | 4 yrs | 19 yrs | 9 yrs | 8 yrs | 7 yrs | |
| Additional Diagnoses | NA | NA | NA | (Family history of consanguinity) | Phenylketonuria | NA | NA | NA | de novo, likely pathogenic variant in FZD2 | NA | |
| PHENOTYPES | Summary | ||||||||||
| Head and neck | ✚ | ✚ | ✚ | ✚ | ✚ | ✚ | NP | 6 / 10 | |||
| Dysmorphic features | Hypertelorism, short philtrum, prognathia | Hypertelorism, epicanthus, down turned mouth corners | Heavy eyebrows, synophrys, large palpebral fissures | Bushy eyebrow, short philtrum | NP | ✚ | NP | 5 / 10 | |||
| Microcephaly | ✚ | ✚ | – | – | ✚ | ✚ | NP | 4 / 10 | |||
| Optic atrophy | Pale optic disc | Pale optic disc | ✚ | – | ✚ | ✚ | NP | 5 / 10 | |||
| Cataract | ✚ | – | ✚ | – | NP | NP | NP | 2 / 10 | |||
| Visual impairment, others such as cortical visual impairment | – | – | Cortical | – | ✚ | Cortical | NP | 3 / 10 | |||
| Strabismus | ✚ | ✚ | ✚ | – | NP | NP | NP | 3 / 10 | |||
| Nystagmus | ✚ | ✚ | – | – | NP | NP | NP | 2 / 10 | |||
| Central nervous system | ✚ | ✚ | ✚ | ✚ | ✚ | ✚ | 4 / 4 | 10 / 10 | |||
| Hypotonia | Infantile | Infantile | Infantile | NP | Infantile | Infantile | 3 / 4 | 8 / 10 | |||
| Delayed psychomotor development | ✚ | ✚ | ✚ | ✚ | ✚ | ✚ | 3 / 4 | 9 / 10 | |||
| Intellectual disability | ✚ | ✚ | ✚ | Mild | ✚ | NP | 3 / 4 | 8 / 10 | |||
| Poor or absent speech | ✚ | ✚ | ✚ | ✚ | ✚ | NP | NP | 5 / 10 | |||
| Seizures | – | – | ✚ | – | ✚ | ✚ | NP | 3 / 10 | |||
| Structural brain malformation on MRI | Cerebellar and cerebral atrophy | Cerebellar and cerebral atrophy | Thin corpus callosum and periventricular white matter | Arachnoid cyst | ✚ | ✚ | NP | 6 / 10 | |||
| Cerebellar ataxia/dysmetria | ✚ | ✚ | – | – | NP | NP | NP | 2 / 10 | |||
| Cerebral atrophy | ✚ | ✚ | ✚ | – | ✚ | ✚ | NP | 5 / 10 | |||
| Cerebellar atrophy | ✚ | ✚ | ✚ | – | ✚ | ✚ | NP | 5 / 10 | |||
| Spasticity (Upper/lower) | Lower limb, started at 15 yrs | – | ✚ | ✚ | ✚ | NP | 2 / 4 | 6 / 10 | |||
| Dystonia | – | – | ✚ | – | NP | ✚ | 2 / 4 | 4 / 10 | |||
| Hypertonia | – | – | ✚ | – | NP | NP | 3 / 4 | 4 / 10 | |||
| Hyperreflexia | ✚ | ✚ | – | – | NP | NP | NP | 2 / 10 | |||
| Upper motor neuron findings (extensor plantar response, ankle clonus) | – | ✚ | – | – | NP | NP | NP | 1 / 10 | |||
| Developmental regression | – | – | – | – | NP | ✚ | 1 / 4 | 2 / 10 | |||
| Progressive disorder | ✚ | – | – | – | NP | NP | NP | 1 / 10 | |||
| Other neuropsychiatric disorder | – | – | – | Autism spectrum | NP | NP | 1 / 4 ADHD | 2 / 10 | |||
| Peripheral nervous system | ✚ | ✚ | ✚ | ✚ | NP | NP | NP | 4 / 10 | |||
| Weakness | ✚ | ✚ | ✚ | ✚ | NP | NP | NP | 4 / 10 | |||
| Hyporeflexia/areflexia | – | – | – | ✚ | NP | NP | NP | 1 / 10 | |||
| Distal sensory loss | NP | NP | NP | ✚ | NP | NP | NP | 1 / 10 | |||
| Allodynia | – | – | – | – | NP | NP | NP | 0 / 10 | |||
| Axonal neuropathy on EMG/NCS | NP | NP | NP | ✚ | NP | NP | NP | 1 / 10 | |||
| Muscle paralysis | – | – | – | – | NP | NP | NP | 0 / 10 | |||
| Musculoskeletal | ✚ | ✚ | ✚ | ✚ | ✚ | NP | 2 / 4 | 7 / 10 | |||
| Short stature | ✚ | ✚ | – | – | NP | NP | 1 / 4 | 3 / 10 | |||
| Joint contractures including camptodactyly | Camptodactyly | – | ✚ | – | NP | NP | NP | 2 / 10 | |||
| Scoliosis | ✚ | – | ✚ | Mild | NP | NP | 1 / 4 | 4 / 10 | |||
| Hip subluxation | Bilateral | Right side | Positive, unspecified laterality | – | NP | NP | NP | 3 / 10 | |||
| Coxa valga/vara | – | – | Bilateral coxa valga | NP | NP | NP | NP | 1 / 10 | |||
| Foot anomaly (pes planus/clubfoot) | Pes planus | Talus valgus | – | Clubfoot | Clubfoot | NP | NP | 4 / 10 | |||
| Muscle atrophy | – | – | – | ✚ | NP | NP | NP | 1 / 10 | |||
| Cataplexy | Gelastic | – | – | NP | NP | NP | NP | 1 / 10 | |||
| Urinary system | ✚ | ✚ | NP | – | NP | ✚ | 1 / 4 | 4 / 10 | |||
| Sphincter disturbances | Incontinent | Incontinent | NP | – | NP | NP | NP | 2 / 10 | |||
| Neurogenic bladder | – | – | – | – | NP | NP | 1 / 4 Neurogenic bowel and bladder | 1 / 10 | |||
| Hydronephrosis | – | – | – | – | NP | ✚ | NP | 1 / 10 | |||
| Structural anomalies | Left duplicated collecting system | – | – | – | NP | NP | NP | 1 / 10 | |||
| Gastrointestinal system | – | – | GERD, constipation | – | NP | NP | NP | 1 / 10 | |||
| Skin/Integument | – | – | Hypertrichosis, cutis marmorata | – | NP | NP | NP | 1 / 10 | |||
Abbreviations are as follows: + = positive; – = negative; NP = not phenotyped or reported