FAQs.

Pogz Disorder is a rare genetic neurodevelopment disorder caused by a mutation in the POGZ gene. Pogz gene is one of the most important genes for early brain development and when impaired, causes cognitive, physical disabilities and other medical complexities.

Every child born with Pogz Disorder is unique as Pogz manifests as a spectrum where symptoms and severity vary between individuals. Current patient data shows characteristics of children with Pogz disorders include: nonverbal, cortical vision impairment, vomiting issues, movement disorders, developmental delays, gastrointestinal issues and Autism. POGZ is also a top ten autism risk gene. Common facial features of POGZ gene disorder includes microcephaly, broad forehead, midface hypoplasia, triangular mouth, broad nasal root and flat nasal bridge.

The POGZ gene provides instructions for making a protein that is found in the cell nucleus. The POGZ protein is part of a group known as zinc finger proteins, which contain one or more short regions called zinc finger domains. These regions include a specific pattern of protein building blocks (amino acids) and one or more charged atoms of zinc (zinc ions). The folded configuration of the zinc finger domain stabilizes the protein and allows it to attach (bind) to other molecules.

In the cell nucleus, the POGZ protein attaches (binds) to chromatin, which is the network of DNA and proteins that packages DNA into chromosomes. Binding of the POGZ protein is part of the process that changes the structure of chromatin (chromatin remodeling) to alter how tightly regions of DNA are packaged. Chromatin remodeling is one way gene activity (expression) is regulated; when DNA is tightly packed gene expression is lower than when DNA is loosely packed. Regulation of gene expression by the POGZ protein is thought to be important to brain development, but the specific function of POGZ in the brain is not well understood.

Pogz disorder is typically a "de novo" (spontaneous, non-inherited) mutation that occurs in one of the two copies of the Pogz gene. This means that patients express one healthy copy and one mutated copy or variant.

Based on limited data available, the mutations (or variants) that occur in the Pogz gene and cause Pogz disorder include splice site, frameshift, missense, nonsense, and deletions.

POGZ gene disorder is a recently-identified genetic disorder resulting from de novo heterozygous pathogenic variants in POGZ. Thus far, over 50 individuals have been reported worldwide, however phenotypic characterization and data regarding the natural history are still incomplete.

Analysis from clinical laboratory database reveals that POGZ variants were implicated in approximately 0.14% of cases who underwent clinical exome sequencing for neurological indications with or without involvement of other body systems.

Since the signs and symptoms of Pogz disorders are common with many neurological disorders, a genetic sequencing test is needed, called Whole Exam Sequencing. Your neurologist, geneticist or pediatrician should be able to submit your child's blood sample to genetic testing companies to get the test completed

Currently, there is no cure for Pogz Disorder. Treatment focuses on managing symptoms through therapies such as speech, occupational, and behavioral therapies.

FOXP1 and POGZ are both genes linked to neurodevelopmental disorders, but they have different roles:

• FOXP1: A transcription factor crucial for brain regions involved in language, social behavior, and motor skills. Mutations lead to developmental delays, autism, and intellectual disability, often with physical growth issues.

• POGZ: Involved in chromatin organization, affecting overall gene expression during brain development. Mutations cause POGZ-related syndrome.White-Sutton syndrome, characterized by intellectual disability, autism, and distinctive facial features.

Both genes have distinct impacts on brain development and function.

Pogz Disorder is typically caused by de novo mutations, meaning they are new mutations that occur spontaneously and are not inherited from the parents.