Akademik Məlumat İdarəetmə Sistemi
Abstracts of the 46th Annual Meeting of the Society for Neuropediatrics, Stuttgart, Germany, 5 - 07 November 2021, pp.52
Background/Purpose: Mutations in the DIAPH1 gene are known etiologies of autosomal dominant hearing disorders. A gain-of-function mechanism is suspected. However, loss-of-function mutations with autosomal recessive inheritance were first reported in the literature in 2015 as causative for early childhood encephalopathies and microcephaly.
Methods Case Report: We described a 12-month-old female infant with developmental disability, epileptic seizures, cortical blindness and microcephaly. Deep ictal apneas and orofacial myoclonic seizures were present from the early neonatal period. Electroencephalography showed series of focal epileptic discharges in the parieto-occipital region. The course of epilepsy was primarily refractory (phenobarbital, levetiracetam, topiramate, lamotrigine). At the age of 7 months, the child revealed global developmental delay (Bayley Scales III, developmental age: 4 months). Crial MRI and hearing tests were unremarkable.
Results: By trio-exome sequencing, two previously undescribed mutations in the DIAPH1 gene were identified in our patient (1. c.3116dup, p.(Asp1039Glufs*15) heterozygous, 2. c3490C>T, p.(Arg1164*) heterozygous). The mother was characterized as heterozygous carrier of the sequence variant c.3116dup, p.(Asp1039Glufs*15) in the DIAPH1 gene. The second (known) variant, c3490C>T, p.(Arg1164*) in the DIAPH1 gene was detected in the father. Thus, a compound heterozygosity in the DIAPH1 gene could be confirmed in the patient.
Conclusion: Early onset DIAPH1-associated epileptic encephalopathies with central blindness have only been described with compound heterozygous inheritance. The compound heterozygosity for loss-of-function mutations in the DIAPH1A gene demonstrated in our case, maternally inherited mutation c.3116dup, p.(Asp1039Glufs*15) and the paternally inherited mutation c3490C>T, p.(Arg1164*) has not previously been reported in the literature.