Table 2.
Summary of the Clinical Features in Cases with DNMs in NTRK2 (GenBank: NM_006180.4)
| Individual | Gender | Age at Last Examination | DNM (Detection) | Cognitive and Behavioral Features | Epilepsy Diagnosis | Age at Seizure Onset | Seizure Types | AEDs | EEG | Brain MRI | Associated Neurological Features and Seizure Outcome |
|---|---|---|---|---|---|---|---|---|---|---|---|
| HSC0103 | male | 2 years, 9 months | c.1301A>G (p.Tyr434Cys) (WGSa) | severe GDD | IS | 3 days | ES, Fo | VGB, ACTH, LEV, CLB, TPM, VPA | modified hyps. | optic nerve hypoplasia | limb hypertonia and hyperreflexia, acquired microcephaly, visual impairment, swallowing difficulties, intractable seizures |
| indvSLIJ | male | 6 years, 3 months | c.1301A>G (p.Tyr434Cys) (cWESb) | severe ID, ASD | DEE | 12 hr with recurrence at 5 years | M, FIA | OXBZ, DZP | DS, TIRDA | optic nerve hypoplasia | hypotonia, lower-limb spasticity, visual impairment, seizures controlled on OXBZ for 1 month |
| T25821 | female | 4 years, 7 months | c.1301A>G (p.Tyr434Cys) (MIPS) | severe GDD, severe ID | IS | 4 months | ES, To | prednisolone, VGB, B6, LEV, CLB, TPM, LCM, KD, VPA, RFN, ZNS, CBD, DZP, PHT | MF, hyps. | optic nerve hypoplasia, myelination delay | acquired microcephaly, hypotonia, subtle choreoathetosis, visual impairment, feeding difficulties, intractable seizures, high tolerance to painful stimuli (parents report) |
| HF303 | male | 4 years, 3 months | c.1301A>G (p.Tyr434Cys) (cWESb, WGSc) | severe GDD, suspected severe ID, ASD | IS | 4 months | ES, FIA | PB, LEV, ACTH, VGB, CLB, ZNS, DZP, CBD | DS, MF | optic nerve hypoplasia | limb hypotonia, visual impairment, swallowing difficulties, intractable seizures, high tolerance to painful stimuli (parents report) |
| HSJ0335 | female | 9 years | c.2159C>T (p.Thr720Ile) (WGSa) | GDD, moderate to severe ID, ASD | DEE | 2.5 years (febrile size at 23 months) | febrile, FIA, GTC, SE | CLB, LEV, TPM, VPA, CBZ | normal, DS after SE | delayed myelination, reduced WM, ventriculomegaly, thin CC | swallowing difficulties, hyperphagia after 3 years of age, no seizures for 2 years under CBZ |
Underlining indicates treatment with clinical response (decreased seizure frequency or severity), and italics indicates a negative response (aggravation of seizure frequency and/or severity). Abbreviations are as follows: WGS, whole-genome sequencing; cWES, clinical whole-exome sequencing; MIPS, molecular inversion probe sequencing; GDD, global developmental delay; ID, intellectual disability; ASD, autism spectrum disorder; IS, infantile spasms; DEE, developmental and epileptic encephalopathy; Fo, focal; FIA, focal impaired awareness; ES, epileptic spasm; M, myoclonic; To, tonic; GTC, generalized tonic-clonic; SE, status epilepticus; AED, anti-epileptic therapy; ACTH, adrenocorticotropin; B6, vitamin B6; CBD, cannabidiol; CLB, clobazam; CBZ, carbamazepine; DZP, diazepam; KD, ketogenic diet; LCM, lacosamide; LEV, levetiracetam; OXBZ, oxcarbazepine; PB, phenobarbital; PHT, phenytoin; RFN, rufinamide; TPM, topiramate; VGB, vigabatrin; VPA, valproic acid; ZNS, zonisamide; EEG, electroencephalography; hyps., hypsarrhythmia; DS, diffuse slowing; MF, multifocal; TIRDA, temporal intermittent rhythmic delta frequency activity; MRI, magnetic resonance imaging; WM, white-matter tracts; and CC, corpus callosum.
CENet.
GeneDx.
HudsonAlpha study.