HNRNP-RNDDs Signs and Symptoms

The HNRNP-RNDDs are distinct disorders with overlapping clinical traits.

We are an umbrella organization to cover all of the HNRNP-RNDDs. As they have similar mechanisms of disease, it is likely that there are shared therapeutic strategies to uncover.

Fast Facts

At least
~1 in 22,620 individuals have an
HNRNP-RNDD

There are at least 10 HNRNP-RNDDs, and that number is growing

Individually, each HNRNP-RNDD is ultra rare but together they overcome their ultra rare status

Rare Disease: a disease that is diagnosed in less than 200,000 individuals in the US, or less than
1 in 1000 individuals

Ultra-rare Disease: a disease that is diagnosed in less than 1 in 50,000 individuals

The HNRNP-RNDDs

95%

have developmental delay/

intellectual disability

71%

have speech and language delay and/or difficulties

57%

have seizures

55%

have motor skills delay

60%

have behavioral differences, including autism spectrum disorder, ADHD, and anxiety

40%

have differences in brain structure

59%

have hypotonia

36%

have skeletal differences such as scoliosis and hand/feet anomalies

44%

have vision and/or eye problems

65%

have distinct facial features, although they vary by HNRNP-RNDD

This data is from Gillentine et al., 2021 and the continuation of that study

Individual HNRNP-RNDDs

The HNRNP-RNDDs are related but distinct disorders. We have color coded them by which are more related to each other.

Heres what we know is different

HNRNPC-RNDD

HNRNPC-RNDD is one of the newest HNRNP-RNDDs described.

Most individuals with HNRNPC-RNDD have a happy demeanor

HNRNPD-RNDD

HNRNPD-RNDD has only been described in one paper.

Speech is particularly affected
Behavioral differences such as autism spectrum disorder are common
Differences in movement (ataxia, poor coodination, dystonia) have been observed

HNRNPG-RNDD

hnRNPG variants result in Shashi-related intellectual disability, which has only been described in a few families. The disorder is X-linked and only affects males (who have one copy of the X chromosome).

Many have short stature
Hearing is often affected
There are shared differences in facial features

HNRNPH1-RNDD

HNRNPH1-RNDD has multiple papers published on it.

Growth delay is common
Speech is particularly affected
MRI abnormalities are common
Vision and eye issues are common
Differences in facial features are common

HNRNPH2-RNDD

HNRNPH2-RNDD is also known as Bain-type intellectual disability. Mostly girls are affected, but a small number of boys have been reported.

Many individuals have genetic variants that impact the same part of the protein
Growth delay is observed in many individuals
Speech and motor skills are significantly affected
Behavioral differences are common, including autism spectrum disorder, anxiety, and hyperacusis
Vision issues are common
There are consistent facial features

HNRNPK-RNDD

Variants in HNRNPK cause Au-Kline Syndrome.

There are distinct facial features observed in many individuals with Au-Kline Syndrome.
Skeletal differences, including scoliosis, are common
~20% of cases have craniosynostosis
Congenital hip dysplasia is common
Many individuals have heart issues

HNRNPR-RNDD

HNRNPR-RNDD has been in two publications.

Many individuals have growth delay
Many have behavioral differences, such as autism spectrum disorder and attention deficit hyperactivity disorder
Skeletal differences have been reported, such as scoliosis or hand and feet differences such as clinodactyly
There are not specific facial features, but many individual have differences in ear structure, and microcephaly is common
Cardiac issues are reported in half of cases

HNRNPQ-RNDD

HNRNPQ/SYNCRIP-RNDD has been in multiple publications.

Most individuals have speech and/or language delay, and many are nonverbal
Behavioral differences such as autism spectrum disorder are common

HNRNPU-RNDD

HNRNPU-RNDD is fairly well characterized, with several publications.

Seizures are reported in almost all cases
Speech and language delay is common

HNRNPUL2-RNDD

HNRNPUL2-RNDD has only one publication.

Growth delay is common
Both speech and motor skills are delayed
Behavioral differences such as autism spectrum disorder and ADHD are common

The HNRNP-RNDDs are distinct disorders with overlapping clinical traits. We are an umbrella organization to cover all of the HNRNP-RNDDs. As they have similar mechanisms of disease, it is likely that there are shared therapeutic strategies to uncover.