Last updated:
9/9/2025
Years published: 2025
NORD gratefully acknowledges Megan Wassef, DO, Pediatric Resident, Paul Hillman, MD, PhD, and Kate Richardson, MS, CGC, McGovern Medical School at the University of Texas Health Science Center at Houston (UTHealth) and Children’s Memorial Hermann Hospital, for the preparation of this report.
Summary
ACCES syndrome, also known as aplasia cutis congenita with ectrodactyly skeletal syndrome, typically presents in early infancy or early childhood and is characterized by developmental delays, learning difficulties, distinctive facial features and skin abnormalities. It is caused by changes (disease-causing variants) in the UBA2 gene and follows an autosomal dominant inheritance pattern.1 While there is no cure, treatments focus on managing symptoms through therapies and educational support to improve the quality of life for affected individuals.
Introduction
The first report of individuals with ACCES syndrome was in 2017. A case series was published in 2021, which reported 21 people from 11 unrelated families.1 As our understanding of genetics and its association with disease evolves, we will continue to learn more about this condition
ACCES syndrome is usually identified in infancy or early childhood when developmental delays or congenital anomalies are noted.1 This condition has variable expressivity, meaning there is a range of symptoms that can occur in affected people. Some individuals with milder presentations may not be identified until adulthood.1,2
Signs and symptoms of ACCES syndrome may include:1,3
Skin and hair (ectodermal) problems:
ACCES syndrome is caused by changes (disease-causing variants) in the UBA2 gene. Genes are the body’s instruction manual for creating proteins that play critical roles in the body. UBA2 encodes a protein known as SUMO-activating enzyme subunit 2 (SAE2). SAE2 contributes to the sumolyation pathway by forming a heterodimer with SUMO-activating enzyme E1 complex (SAE1) and activates the SUMO protein.3,4 Sumoylation is a post-translational modification that adds small ubiquitin-like modifiers (SUMO protein) to a target protein. This process is important in embryonal development and formation of limbs.2 You can think of sumoylation as placing a post-it note on a protein inside the cells, where this note is guiding the protein on its specific role. Defects in production of SAE2 can affect various processes like increasing the number of cells (cellular proliferation) and cells moving to locations for proper body development (cell migration).
Inheritance
ACCES syndrome follows autosomal dominant inheritance with most cases being de novo.1,3 Dominant genetic disorders occur when only a single copy of a disease-causing gene variant is necessary to cause the disease. The gene variant can be inherited from either parent or can be the result of a new (de novo) gene change in the affected individual that is not inherited. The risk of passing the gene variant from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females.
As of July 2025, 24 cases have been reported in the medical literature.1,3,5
ACCES syndrome is extremely rare. The number of people affected by this disorder is unknown. Rare disorders often go undiagnosed or misdiagnosed, making it extremely difficult to determine their true frequency in the general population. With available information currently, males and females as well as all ethnicities are affected equally. Age of onset is typically in infancy or childhood.
ACCES syndrome may suspected based on the following signs and symptoms:1
The diagnosis of ACCES syndrome is confirmed when genetic testing identifies a disease-causing (pathogenic) variant in the UBA2 gene.
There is no cure for ACCES syndrome, so treatment focuses on managing symptoms. Individuals with developmental delays, learning difficulties and behavioral issues should receive additional support with the appropriate therapies. These services include speech therapy, occupational therapy, physical therapy, applied behavioral analysis and various school programs such as an individualized educational plan (IEP) and 504b plan (roadmap for accommodations for a specific student).
Individuals may have congenital heart defects, genitourinary anomalies and hip abnormalities. Therefore, it is advised that patients have an echocardiogram (picture of the heart) evaluated by a cardiologist, an abdominal ultrasound (picture of the abdominal organs, such as the kidneys), renal function tests (blood or urine tests to tell you how well the kidneys are working) and hip X-rays.
In addition, individuals who are family planning may benefit from prenatal genetic counseling to learn more about potential risks to future children and reproductive options available.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, in the main, contact: www.centerwatch.com
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/No patient organizations found related to this disease state.
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