| Autor: |
Orsini A; Pediatric Neurology, Pediatric Department, AOUP Santa Chiara Hospital, 56100 Pisa, Italy., Santangelo A; Pediatric Neurology, Pediatric Department, AOUP Santa Chiara Hospital, 56100 Pisa, Italy.; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16126 Genoa, Italy., Carmignani A; Pediatric Department, AOUP Santa Chiara Hospital, 56100 Pisa, Italy., Camporeale A; Pediatric Department, AOUP Santa Chiara Hospital, 56100 Pisa, Italy., Massart F; Pediatric Endocrinology, Pediatric Department, AOUP Santa Chiara Hospital, 56100 Pisa, Italy., Tyutyusheva N; Pediatric Endocrinology, Pediatric Department, AOUP Santa Chiara Hospital, 56100 Pisa, Italy., Peroni DG; Pediatric Department, AOUP Santa Chiara Hospital, 56100 Pisa, Italy., Foiadelli T; Clinica Pediatrica, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy., Ferretti A; Pediatrics Unit, Neuroscience, Mental Health and Sense Organs (NESMOS) Department, Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy., Toschi B; Division of Medical Genetics, Department of Medical and Oncological Area, University-Hospital, 56126 Pisa, Italy., Romano S; Division of Medical Genetics, Department of Medical and Oncological Area, University-Hospital, 56126 Pisa, Italy., Bonuccelli A; Pediatric Neurology, Pediatric Department, AOUP Santa Chiara Hospital, 56100 Pisa, Italy. |
| Abstrakt: |
The adaptor protein 4 (AP-4) constitutes a conserved hetero-tetrameric complex within the family of adaptor protein (AP) complex, crucial for the signal-mediated trafficking of integral membrane proteins. Mutations affecting all subunits of the AP-4 complex have been linked to autosomal-recessive cerebral palsy and a complex hereditary spastic paraparesis (HSP) phenotype. Our report details the case of a 14-year-old boy born to consanguineous parents, presenting psychomotor delay, severe intellectual disability, microcephaly, and trigonocephaly. Despite a history of febrile seizures, subsequent years were devoid of seizures, with normal EEG. Exome sequencing revealed pathogenic variants in both the AP4B1 and ERF genes. Significantly, the patient exhibited features associated with AP4B1 mutations, including distinctive traits such as cranial malformations. The ERF gene variant, linked to craniosynostosis, likely contributes to the observed trigonocephaly. This case represents the initial documentation of a concurrent mutation in the AP4B1 and ERF genes, underscoring the critical role of exome analysis in unraveling complex phenotypes. Understanding these complex genotypes offers valuable insights into broader syndromic conditions, facilitating comprehensive patient management. |
