To provide a detailed electroclinical description and expand the phenotype of PIGT-CDG, to perform genotype–phenotype correlation, and to investigate the onset and severity of the epilepsy associated with the different genetic subtypes of this rare disorder. Furthermore, to use computer-assisted facial gestalt analysis in PIGT-CDG and to the compare findings with other glycosylphosphatidylinositol (GPI) anchor deficiencies.
We evaluated 13 children from eight unrelated families with homozygous or compound heterozygous pathogenic variants in PIGT.
All patients had hypotonia, severe developmental delay, and epilepsy. Epilepsy onset ranged from first day of life to two years of age. Severity of the seizure disorder varied from treatable seizures to severe neonatal onset epileptic encephalopathies. The facial gestalt of patients resembled that of previously published PIGT patients as they were closest to the center of the PIGT cluster in the clinical face phenotype space and were distinguishable from other gene-specific phenotypes.
We expand our knowledge of PIGT. Our cases reaffirm that the use of genetic testing is essential for diagnosis in this group of disorders. Finally, we show that computer-assisted facial gestalt analysis accurately assigned PIGT cases to the multiple congenital anomalies–hypotonia–seizures syndrome phenotypic series advocating the additional use of next-generation phenotyping technology.
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Shared first authors: Allan Bayat, Alexej Knaus, Annika Wollenberg Juul.
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We thank the families for participating in this study. We thank Malin Kvarnung for kindly sharing previously unpublished data regarding the onset of epileptic seizures in their patients. I.H. was supported by intramural funds of the University of Kiel, and by a grant from the German Research Foundation (DFG) (HE5415/6-1). Y.W. was supported by a grant from the German Research Foundation (DFG) (WE4896/3-1 and WE4896/4-1). A.C. was sponsored by Polish National Science Centre grant number 2014/15/D/NZ5/03426. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (WT098051). The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network. The views expressed in this publication are those of the authors and not necessarily those of the Wellcome Trust or the Department of Health.