Table 1.
Clinical features of ten patients with rare and novel biallelic and monoallelic variants in PLXNA1.
| Family ID | Family A | Family C | Family D | Family E | Family F | Family G | Family H | |||
|---|---|---|---|---|---|---|---|---|---|---|
| Patient | II-2 | II-1 | II-2 | II-3 | II-1 | II-2 | II-1 | II-1 | II-1 | II-1 |
| Zygosity | Compound heterozygous | Compound heterozygous | Homozygous | Homozygous | De novo | De novo | De novo | |||
| c.356T>C, p.(Leu119Pro) c.3230G>A, p.(Arg1077His) |
c.1549C>T, p.(Gln517*) c.2446T>C, p.(Cys816Arg) |
c.1574_1575del, p.(Leu525Argfs*23) | c.2641C>T, p.(Arg881Trp) | c.3554G>A, p.(Arg1185Gln) | c.4483C>T, p.(Arg1495Trp) | c.5242C>T, p.(Arg1748Cys) | ||||
| gnomAD MAF% | NR; 0.003% (hom=0) | 0.001% (hom=0); NR | NR | 0.0004% (hom=0) | 0.001% (hom=0) | NR | NR | |||
| GDD | Yes | Yes | Yes | Yes | Yes | Yes | Noa | Yes | Yes | Yes |
| Seizures | 15 episodes of febrile and nonfebrile | - | - | - | - | - | - | Neonatal-onset absence-like | Generalized tonic–clonic | Neonatal-onset atonic |
| Craniofacial anomalies | - | - | Cupped ears, small teeth, microcephaly | - | Sparse lateral eyebrows, depressed nasal bridge, large earlobes, short neck | - | High forehead, hypertelorism, posteriorly rotated ears, smooth philtrum | Unilateral facial palsy, dysmorphic right auricle | Macrocephaly, mild face hypotrophy | |
| Eye anomalies | - | - | Ptosis | Nystagmus | Optic disc hypoplasia, strabismus, mild ptosis | - | Mild ptosis | Optic disc hypoplasia, impaired vision | Enophthalmia | |
| Cerebral anomalies | - | - | Dysplastic “mega” CC | - | Dysmorphic VS, prominent Virchow–Robins spaces | Agenesis of CC, colpocephaly | Several bilateral high signal foci in the subcortical white matter | Normal brain MRI | Enlarged VS, thin CC, brainstem hypoplasia, agenesis of the posterior pituitary | Periventricular leukoencephalopathy, basal ganglia calcifications, subtentorial atrophy |
| Neurologic findings | - | - | Unitateral sensorineural hearing loss, ASD | - | ADHD, ASD | Bilateral peripheral axonal neuropathy | Lower limb hyper-reflexia, ASD | Muscular hypotonia | Bilateral sensorineural hearing loss, vestibule-cochlear nerve agenesis, muscular hypotonia | Spastic paraparesis, pyramidal signs |
| Other | Hypoplastic right kidney | VUR | - | Hypopigmented skin lesions | Elevated CK, hypo- and hyperpigmented skin | IUGR, DCM, joint hypermobility, hand bone and rib anomalies | Dextrocardia, SVC, esophageal atresia | - | ||
ADHD attention deficit hyperactivity disorder, ASD autism spectrum disorder, CC corpus callosum, CK creatine kinase, CSF cerebrospinal fluid, DCM dilated cardiomyopathy, GDD global developmental delay, IUGR intrauterine growth restriction, MAF minor allele frequency, MRI magnetic resonance image, NR not reported, SVC left-sided superior vena cava, VS ventricular system, VUR vesicoureteral reflux.
aIsolated language regression.