Autistic Behavior as Novel Clinical Finding in OFD1 Syndrome.

Researchers reported on a 3-year-old girl with a rare genetic condition called OFD1 syndrome who also showed signs of autism. This is the first time autism has been documented in a female with this syndrome. The girl had typical features of the syndrome including mouth problems, severe speech delays, and brain differences, plus autistic behaviors. The researchers suggest doctors should watch for autism signs in children with this syndrome.

This case report describes a 3-year-old girl with OFD1 syndrome who presented with autistic behaviors alongside typical syndrome features including oral malformations, severe speech delay, developmental delay, and brain abnormalities. The patient had a pathogenic variant in the OFD1 gene, which is involved in cilia formation and brain development. This represents the first documented case of autism in a female with OFD1 syndrome. The authors suggest that autistic behavior should be considered a potential feature of OFD1 syndrome and recommend active screening for early autism signs in patients with this rare ciliopathy.

Clinicians managing OFD1 syndrome patients should consider screening for autism spectrum features. Early identification could facilitate timely interventions. This case highlights the need for systematic studies examining autism prevalence in ciliopathy syndromes and broader neurodevelopmental surveillance in rare genetic conditions.

Single case report limits generalizability. No systematic assessment tools for autism diagnosis described. Lacks comparison with other OFD1 syndrome cases or control data. Cannot establish causality between OFD1 gene variant and autistic behaviors.

Orofaciodigital syndrome I (OFD1-MIM #311200) is a rare ciliopathy characterized by facial dysmorphism, oral cavity, digit, and brain malformations, and cognitive deficits. OFD1 syndrome is an X-linked dominant disorder reported mostly in females. The gene responsible for this condition, OFD1 centriole and centriolar satellite protein (), is involved in primary cilia formation and several cilia-independent biological processes. The functional and structural integrity of the cilia impacts critical brain development processes, explaining the broad range of neurodevelopmental anomalies in ciliopathy patients.

As several psychiatric conditions, such as autism spectrum disorders (ASD) and schizophrenia, are neurodevelopmental in nature, their connections with cilia roles are worth exploring. Moreover, several cilia genes have been associated with behavioral disorders, such as autism. We report on a three-year-old girl with a complex phenotype that includes oral malformations, severe speech delay, dysmorphic features, developmental delay, autism, and bilateral periventricular nodular heterotopia, presenting a de novo pathogenic variant in thegene. Furthermore, to the best of our knowledge, this is the first report of autistic behavior in a female patient with OFD1 syndrome.

We propose that autistic behavior should be considered a potential feature of this syndrome and that active screening for early signs of autism might prove beneficial for OFD1 syndrome patients.