PIGA -related epileptic encephalopathy demonstrating intrafamilial phenotypic heterogeneity
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LETTER TO THE EDITOR
PIGA‑related epileptic encephalopathy demonstrating intrafamilial phenotypic heterogeneity Peren Perk Yucel1 · Hatice Mutlu Albayrak2 Received: 2 March 2020 / Accepted: 8 June 2020 © Belgian Neurological Society 2020
Keywords Epileptic encephalopathy · PIGA · X-linked ID
Introduction Early infantile epileptic encephalopathies (EIEE) are characterized by intractable infantile-onset epilepsy which fail to conventional antiepileptic drugs, accompanying progressive intellectual disability (ID), electroencephalographic abnormalities resulted in cerebral dysfunction. Many of the EIEEs are now known to have identifiable molecular genetic basis [1]. Germline truncating mutations of PIGA (Phosphatidylinositol N acetylglucosaminyltransferase subunit-A) gene are related with a X-linked EIEE, and also named as multiple congenital anomalies hypotonia-seizures syndrome two and Ferro-Cerebro-Cutaneous syndrome (FCCS) [2–4]. We report two male siblings presented with EIEE; severe intellectual disability (ID); coarse facial appearance; hyperferritinemia and various skin findings due to a novel mutation in PIGA.
Case report Two inbred 13-year (P1) and 11-year-old (P2) ambulatorynonverbal males presented with intractable epilepsy and ID were admitted to pediatric neurology clinic. They were born at full-term weighing 5500 gr (> 97th centile) and 2500 gr * Peren Perk Yucel [email protected] Hatice Mutlu Albayrak [email protected] 1
Department of Pediatric Neurology, Gaziantep Cengiz Gokcek Maternity and Children’s Hospital, Sehitkamil, Gaziantep 27010, Turkey
Department of Pediatric Genetics, Gaziantep Cengiz Gokcek Maternity and Children’s Hospital, Sehitkamil, Gaziantep 27010, Turkey
2
( T (p. Thr331I) hemizygous disease-causing variant was identified in PIGA by clinical exome sequencing.
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Acta Neurologica Belgica
Fig. 1 (a–d) P1, demonstrating thick hair, significant dysmorfic facial features including coarse face, prominent chin, macrostomia, macroglossia, gingival hypertrophy and ichthyotic skin lesions on neck
and flexor face of joints. (e–g) P2, with similar facial features, maculopapular skin lesions on the neck and chest; xerosis cutis on extensor face of hands and feet
Discussion
of PIGA protein. Although in the R412X which causes early stop codon, reported by Johnston, the patients were demonstrating EIEE with early infantile lethality; the same mutation was also showed to be associated with EIEE with a suppression-burst pattern on EEG, increased birth weight, and coarse facial features suggesting SGBS without early lethality [4]. Moreover, other PIGA mutations were also described in patients who had systemic iron storage and distinctive cutaneous abnormalities that became apparent only after the onset of neurologic symptoms and named in FCCS [2]. Due to the fact that there is a clinical variability, the genotype–phenotype correlation cannot be established. Current family with T331I missense mutation affecting the cytoplasmic domain, was demonstrating
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