PIGT-CDG, a disorder of the glycosylphosphatidylinositol anchor: description of 13 novel patients and expansion of the clinical characteristics

TY - JOUR

T1 - PIGT-CDG, a disorder of the glycosylphosphatidylinositol anchor

T2 - description of 13 novel patients and expansion of the clinical characteristics

AU - the DDD Study Group

AU - Bayat, Allan

AU - Knaus, Alexej

AU - Juul, Annika Wollenberg

AU - Dukic, Dejan

AU - Gardella, Elena

AU - Charzewska, Agnieszka

AU - Clement, Emma

AU - Hjalgrim, Helle

AU - Hoffman-Zacharska, Dorota

AU - Horn, Denise

AU - Horton, Rachel

AU - Hurst, Jane A.

AU - Josifova, Dragana

AU - Larsen, Line H.G.

AU - Lascelles, Karine

AU - Obersztyn, Ewa

AU - Pagnamenta, Alistair

AU - Pal, Deb K.

AU - Pendziwiat, Manuela

AU - Ryten, Mina

AU - Taylor, Jenny

AU - Vogt, Julie

AU - Weber, Yvonne

AU - Krawitz, Peter M.

AU - Helbig, Ingo

AU - Kini, Usha

AU - Møller, Rikke S.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Purpose: 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. Methods: We evaluated 13 children from eight unrelated families with homozygous or compound heterozygous pathogenic variants in PIGT. Results: 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. Conclusion: 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.

AB - Purpose: 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. Methods: We evaluated 13 children from eight unrelated families with homozygous or compound heterozygous pathogenic variants in PIGT. Results: 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. Conclusion: 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.

KW - computer-assisted facial gestalt analysis

KW - congenital disorder of glycosylation

KW - epilepsy

KW - genotype–phenotype

KW - PIGT-CDG

UR - http://www.scopus.com/inward/record.url?scp=85064261102&partnerID=8YFLogxK

U2 - 10.1038/s41436-019-0512-3

DO - 10.1038/s41436-019-0512-3

M3 - Article

AN - SCOPUS:85064261102

SN - 1098-3600

VL - 21

SP - 2216

EP - 2223

JO - GENETICS IN MEDICINE

JF - GENETICS IN MEDICINE

IS - 10

ER -