Case presentation: D.H.S., male, 23 months, non-consanguineous parents, born at term, pregnancy and
delivery without complications, healthy 7-year-old brother, and no cases of epilepsy
or developmental delay in the family. From birth he had difficulty breastfeeding and
hypotonia, at 3 months he started episodes of behavioral arrest, and at 9 months episodes
of lip cyanosis, hypertonia of the four limbs lasting less than one minute and post-ictal
with exacerbation of hypotonia. At the first hospital evaluation, at 18 months, D.H.S.
had significant neuropsychomotor delay, global hypotonia, hypopigmentation of the
skin and hair, difficulty in eating and sleeping, signs suggestive of autism spectrum
disorder, choreoathetosis, dystonia and refractory epilepsy, Angelman Syndrome (AS)
was one of the diagnostic hypotheses evaluated. In the diagnostic investigation, the
video electroencephalogram showed a generalized electroclinical crisis with a rhythm
starting in bilateral central parietal regions and in the midline, clinically classified
as generalized tonic-clonic motor onset; what would be considered an atypical pattern
in AS, the other tests performed were not elucidative at first for the case. In a
genetic evaluation, the variant c.228A>T (p.Glu76Asp) was identified in the GABRB2
gene in heterozygosity; of uncertain meaning, but potentially deleterious, and may
be the cause of all symptoms presented by the patient.
Discussion: The GABRB2 gene encodes a subunit of the gamma-aminobutyric acid (GABA) receptor,
which is an ion channel involved in inhibitory neurotransmission. Heterozygous pathogenic
variants in GABRB2 are associated with epileptic and developmental encephalopathy.
Therefore, the clinic presented by the patient, refractory epilepsy, movement disorder
and delay in neuromotor development, is consistent with the genetic alteration found.
The variant found is of autosomal dominant inheritance, and although it is classified
as a variant of uncertain significance (VUS), it is possible to consider that this
rare variant is pathogenic.
Final comments: The recent increase in the availability of genetic tests has allowed the diagnosis
of diseases that could previously have been clinically misdiagnosed. In the case of
the patient reported here, in which the typical facial features of AS would not yet
be observed due to age and the clinical picture was compatible, genetic testing was
essential for the differential diagnosis.
