Introduction PACS1 is a trans-Golgi-membrane traffic regulator directing protein cargo. A de novo missense variant in the PACS1 gene was first identified in individuals with intellectual disability and dysmorphism in 2012 and designated as Schuurs-Hoeijmakers syndrome. Epilepsy is frequent and it is reported that seizures respond well to anti-seizure medications. We aim to present unpublished six patients with very rare Schuurs-Hoeijmakers syndrome, some of whom had drug-resistant epilepsy and/or significant EEG abnormalities. Methods We retrospectively collected data from six patients (age 5-33 years) with c.607C>T p.Arg203Trp variant in the PACS1 gene identified by whole-exome sequencing from multiple centers. Results All the patients had the same de novo c.607C>T variant as heterozygous. They all had distinctive facial features (hypertelorism, bulbous nasal tip, a flat philtrum, low-set ears). Some patients had cardiac, urogenital, and eye involvement. Optic nerve anomaly resulted in low visual acuity in one patient. Intellectual disability was present in all, ranging from moderate to severe, with some having autistic features. Five patients had epilepsy, one had drug-resistant epilepsy and another was on polytherapy for continuous generalized spike-waves. Ethosuximide was added to valproate and levetiracetam for myoclonic atonic seizures in the drug-resistant patient with a partial response. Conclusion Epilepsy is frequent in our case series even with drug-resistant seizures. Ophthalmological involvement may be severe, resulting in decreased vision. De novo c.607C>T variant is the major variant reported. A gain-of-function effect has been proposed as a reason for the absence of other variants in the gene.

Tugce Aksu Uzunhan
Turkey

Biray Erturk
Prof. Dr. Cemil Tascioglu City Hospital

Bulent Kara
Kocaeli University, Faculty of Medicine

Gozde Yesil
Istanbul University, Faculty of Medicine

Yasemin Karal
Trakya University, Faculty of Medicine

Gulay Gulec Ceyhan

Ali Cansu
Karadeniz Technical University, Faculty of Medicine

Dilek Aktas
Damagen Genetic Diagnostic Center

Dilsad Turkdogan
Marmara University, Faculty of Medicine

Filiz Ozen
Medeniyet University, Faculty of Medicine

Fatma Silan
Canakkale Onsekiz Mart University, Faculty of Medicine

Hasan Tekgul
Ege University, Faculty of Medicine

Meral Topcu
Hacettepe University, Faculty of Medicine