Trinucleotide repeat containing adaptor 6B protein deficiency syndrome – A rare cause for language delay and attention deficit hyperactivity disorder

To the Editor, T rinucleotide repeat containing adaptor 6B protein (TNRC6B) deficiency syndrome, caused by a mutation in the TNRC6B gene, is a very rare autosomal dominant neurodevelopmental disorder with a broad spectrum of clinical features.The TNRC6B gene encodes a protein involved in gene silencing through the microRNA pathway, which is crucial for regulating gene expression during development.Key clinical features are global developmental delay, intellectual disability, autism spectrum disorders (ASD), and attention-deficit hyperactivity disorder (ADHD).Speech and language delays are particularly prominent, ranging from mild impairment to severe expressive and receptive language difficulties.A 15-year-old girl presented to the neurology outpatient department with global developmental delay, subnormal intelligence, ADHD, expressive language disorder, and learning disorder.She had a few episodes of generalized tonic-clonic seizures in childhood and was responsive to anti-seizure medication and was successfully tapered off after 3 years of seizure freedom.On examination, a mild level of intellectual disability (50% disability, predicted IQ score -57, Binet-Kamat intelligence scale IQ -46 [1], Vineland social maturity scale score -63 [2] was observed.There was no facial dysmorphism.There were no neurocutaneous markers.Her basic workup, including thyroid function tests, urine, and serum aminogram, was normal.Her electroencephalogram and magnetic resonance imaging of the brain were normal.In view of a significant language disorder, clinical exome sequencing was ordered, which showed a heterozygous missense variant in exon 5 of the TNRC6B gene (chr22:g.40266716C>T;Depth: ×150) that results in the amino acid substitution of leucine for proline at codon 829 (p.Pro829Leu; ENST00000454349.7).This mutation has not been reported so far in the available literature.Key clinical features are global developmental delay, noticeable in infancy or childhood.Most affected