Axonal motor polyneuropathy in a 13 years old Girl with a de Novo variant in ADNP

ADNP-Related Disorder [previously known as Helsmoortel-Van der Aa syndrome (HVDAS)] is a rare genetic condition resulting from mutations in the activity-dependent neuroprotector homeobox (ADNP) gene. The ADNP protein has multiple functions, including serving as an essential transcription factor for brain development. In addition, pathogenic variants in ADNP have been recognized as one of the most frequent monogenic causes of autism spectrum disorder (ASD) and intellectual disability. Clinical features include craniofacial dysmorphisms, congenital heart defects, gastrointestinal problems such as feeding difficulties, gastroesophageal reflux and frequent vomiting, vision problems, recurrent infections and seizures. Here we describe the novel case of a girl who came to our attention in infancy because of poor and stereotyped motor repertoire, repetitive purposeless movements, and intellectual disability. Whole exome sequencing revealed a de novo heterozygous variant in the ADNP gene, leading to the diagnosis of HVDAS at age 5 years. At the age of 12, nerve conduction velocity testing showed severe four-limb axonal motor polyneuropathy. In this article, we would like to focus on the presence of peripheral nervous system involvement associated with the pathogenic ADNP de novo variant, which may contribute to the clinical characterization of ADNP-Related Disorder.