Genetics

What Causes HNRNP-RNDDs?

Understanding the genetic origins of these rare neurodevelopmental disorders and how they're inherited from generation to generation.

De Novo Variants Inheritance Patterns

Kathleen Morton with her sister and father at the 2024 HNRNP conference

Kathleen Morton (center), who has HNRNPK-NDD or Au-Kline, her sister (left), and father (right) engaged in 2024 foundation conference

Key Concepts

Understanding the Genetics

The essential concepts explained in plain language

De Novo

"Brand New" Variants

Most HNRNP variants happen spontaneously—they're not passed down from parents. The recurrence risk is typically less than 1%.

Dominant

One Copy Matters

Only one changed copy of the gene is needed to cause the condition.

Variable

Different Presentations

Even with the same variant, symptoms can vary widely between individuals. Every person is unique.

Deep Dive

What is a De Novo Variant?

This is the most common way HNRNP-RNDDs occur—and it's no one's fault.

A Spontaneous Change

A de novo variant is a genetic change that occurs for the first time in a family. It happens in an egg or sperm cell, or very early after fertilization. Neither parent carries the variant—it's completely new.

What This Means for Families

Low recurrence riskTypically less than 1% chance in future pregnancies
Not inherited from parentsStandard genetic testing of parents is usually negative
Rare exception: mosaicismIn rare cases, a parent may carry the variant in some cells

Good to Know

Every family's situation is unique. Many families find it helpful to meet with a genetic counselor who can explain their specific circumstances and answer questions.

Inheritance Patterns

How HNRNP Variants Are Passed On

Once a variant exists, it follows specific inheritance patterns

Most Common

Autosomal Dominant

Only one copy of the gene needs to be affected. If a parent has the variant, each child has a 50% chance of inheriting it. Affects males and females equally.

Genes with this pattern:

HNRNPCHNRNPDHNRNPH1HNRNPKHNRNPQHNRNPUHNRNPUL1HNRNPUL2

X Chromosome

X-Linked

The gene is located on the X chromosome. Because males have one X (XY) and females have two (XX), these conditions may present differently between sexes.

Genes with this pattern:

HNRNPH2RBMX

Variant Types

Types of Genetic Changes

Different types of variants can affect HNRNP genes. The type may help predict how the condition presents.

Missense

A single "letter" is swapped, changing one amino acid of the protein. This can change how the protein functions.

Frameshift

Letters are added or removed, scrambling the genetic message downstream. This results in loss-of-function or a shorter version of the protein.

Nonsense

A change creates a premature "stop" signal, making the protein too short. This results in loss-of-function or a shorter version of the protein.

Structural

Larger sections of DNA are deleted, duplicated, or rearranged.