Bibliographic Details
| Title: |
Broadening the PHIP-Associated Neurodevelopmental Phenotype |
| Authors: |
Giulia Pascolini, Giovanni Luca Scaglione, Balasubramanian Chandramouli, Daniele Castiglia, Giovanni Di Zenzo, Biagio Didona |
| Source: |
Children, Vol 11, Iss 11, p 1395 (2024) |
| Publisher Information: |
MDPI AG, 2024. |
| Publication Year: |
2024 |
| Collection: |
LCC:Pediatrics |
| Subject Terms: |
PHIP, neurodevelopment, Chung–Jansen syndrome (CHUJANS), Pitt–Hopkins syndrome (PTHS)-like phenotype, abnormal skin appendages, teeth anomalies, Pediatrics, RJ1-570 |
| More Details: |
Background: Monoallelic damaging variants in PHIP (MIM*612870), encoding the Pleckstrin Homology Domain Interacting Protein, have been associated with a novel neurodevelopmental disorder, also termed Chung–Jansen syndrome (CHUJANS, MIM#617991). Most of the described individuals show developmental delay (DD)/intellectual disability (ID), obesity/overweight, and variable congenital anomalies, so the condition can be considered as an ID–overweight syndrome. Case Description: We evaluated a child presenting with DD/ID and a craniofacial phenotype reminiscent of a Pitt–Hopkins syndrome (PTHS)-like condition. We performed a clinical exome analysis on his biological sample, as well as an in silico prediction of the obtained data. At the same time, we interrogated the DeepGestalt technology powered by Face2Gene (F2G), using a frontal image of the proband, and clinically reviewed the earlier CHUJANS patients. In this child, we found a novel PHIP pathogenetic variant, which we corroborated through a protein modeling approach. The F2G platform supported the initial clinical hypothesis of a PTHS-like condition, while the clinical review highlighted the lack of the main frequent CHUJANS clinical features in this child. Conclusions: The unusual clinical presentation of this novel patient resembles a PTHS-like condition. However, a novel variant in PHIP has been unexpectedly detected, expanding the phenotypic spectrum of CHUJANS. Notably, PTHS (MIM#610954), which is a different ID syndrome caused by heterozygous variants in TCF4 (MIM*610954), is not classically considered in the differential diagnosis of CHUJANS nor has been cited in the previous studies. This could support other complex diagnoses and invite further patients’ descriptions. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
2227-9067 |
| Relation: |
https://www.mdpi.com/2227-9067/11/11/1395; https://doaj.org/toc/2227-9067 |
| DOI: |
10.3390/children11111395 |
| Access URL: |
https://doaj.org/article/86293e5e4581412a8fc4657b8d38956a |
| Accession Number: |
edsdoj.86293e5e4581412a8fc4657b8d38956a |
| Database: |
Directory of Open Access Journals |
