Some clinically distinctive syndromes have not yet been explained by single gene mutations or CNVs. They are likely heterogeneous and a few tentative implications of genetic causes have been published. Could they involve non-coding elements? Epigenetic mechanisms? Unknown rare teratogens or rare teratogenXgene interactions?
|Amyoplasia Congenita Disruptive Sequence|
|Cervico-Oculo-Acoustic Syndrome (Wildervanck)|
* Dubowitz Syndrome is probably a collection of heterogeneous disorders with phentype overlap.
20% of Toriello-Carey Syndrome patients have a pathogenic CNV, and some may have de novo mutations in DDX3X
We should consider a concerted effort to close the diagnostic gap on these specific conditions while we are working on the larger problem of birth defects and malformations. Experts who have patient collections: now is the time to carry out trio whole genome sequencing. Contact me.