ARRE Foundation celebrates milestone publication for Shashi-Pena Syndrome (ASXL2)
We are excited to announce a new publication on Shashi-Pena Syndrome, a collaborative effort between the ARRE Foundation, the family community, and medical experts. This paper, published as a new chapter in GeneReviews, is the first comprehensive update on Shashi-Pena Syndrome since 2016. It expands the medical understanding of the syndrome’s key features, analyzing data from 23 individuals.
The publication provides updated symptom data and introduces guidelines for care, outlining recommended specialists and evaluations for those newly diagnosed. Key findings include new details on dental abnormalities, hearing loss, and bone fragility—symptoms familiar to many families but had never been reported in the medical literature. This reference will be an invaluable tool for clinicians, families, and researchers seeking a deeper understanding of Shashi-Pena Syndrome and tailored care recommendations.
This paper is truly a collaboration between the ARRE Foundation, the Shashi-Pena Syndrome family community, and the team of dedicated medical professionals who completed the study. With our strong connections to the family and research community, the ARRE Foundation advocated for this project knowing the family community was growing and there were enough patients willing to contribute data to the project to justify doing it.
This paper is truly a collaboration between the ARRE Foundation, family community, and the medical professionals who wrote the paper. The ARRE Foundation advocated for the medical professionals to write it because we knew the family community was growing and there were enough patients willing to contribute data to the project to justify doing it.
New findings in this paper include:
Dental abnormalities
Hearing loss
Bones that fracture easily
These are issues that are well known to the family community. The ARRE Foundation was able to flag these issues with the medical professionals who wrote the paper as items to ask about when interviewing families during the data collection part of the project.
Summary of clinical findings
A summary of the updated findings and their prevalence from the 23 patients included in this study include:
Facial birthmark (glabellar nevus simplex) – 100%
Distinctive facial features – 100%
Dental abnormalities – 100%; early tooth growth and loss, fragile teeth
Developmental delays/intellectual disability – 95%
Low muscle tone (hypotonia) – 95%; improves with age
Skin findings – 85%; capillary malformations, deep hand lines, extra hair
Feeding issues in newborns – 85%; may need tube feeding
Feeding issues in childhood – 28%
Bone problems (skeletal anomalies) – 82%; includes scoliosis, hypermobility, and frequent fractures
Heart defects – 81%
Large head size (macrocephaly) – 75%
Vision issues – 73%
Behavior challenges – 71%
Seizures – 67%; includes febrile and non-febrile seizures
Low blood sugar (hypoglycemia) – 65%
Large body size (macrosomia) – 55%
Hearing loss – 47%
Sleep apnea – 47%; may be obstructive or mixed central/obstructive
Temperature regulation issues – 43%
Future work
The GeneReviews chapter includes patients with de novo truncating variants in the last two exons of the ASXL2 gene (this means nonsense, frameshift, and splice variants that are not inherited). These are the specific types of genetic mutations that are known to cause “classic” features of Shashi-Pena Syndrome as originally described in the original 2016 paper that defined the syndrome. Additional future study is needed to describe the variable features and symptoms of individuals who have other types of ASXL2 variants, including missense variants.
Our thanks to the medical team:
We are extremely grateful to Dr. Vandana Shashi, Dr. Loren Peña, Dr. Julie Porter, and Becky Spillman for their efforts in completing this publication.
Our thanks to Shashi-Pena Syndrome families:
We extend a huge thanks to the Shashi-Pena Syndrome families who contributed their knowledge and experience to this publication through interviews and medical records. Your contributions will make another family’s journey with Shashi-Pena Syndrome a bit less uncertain in the future. Thank you.
