Unsolved Recognizable Syndromes

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?

Genetic Disorder

*Dubowitz Syndrome

Hallermann-Streiff Syndrome

Wieddemann-Rautenstrauch Syndrome

Amyoplasia Congenita Disruptive Sequence

Fryns Syndrome

Cervico-Oculo-Acoustic Syndrome (Wildervanck)

Mohr Syndrome (OFD Type II) Poland Sequence Femoral Hypoplasia-Unusual Facies Syndrome Aase Syndrome Acrodystosis Syndrome *Toriello-Carey Syndrome Oculo-Auriculo-Vertebral Spectrum Oromandibular-Limb Hypogenesis Spectrum (overlaps with Mobius syndrome) Congenital Microgastria-Limb Reduction Complex Sternal Malformation-Vascular Dysplasia (PHACES Syndrome) MURCS Association (Mayer-Rokitansky-Küster-Hauser Type 2)

* 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.