[Clinical and genetic characteristics of 6 children with acrodysostosis].

Objective

To analyze the clinical, radiographic, and genetic characteristics of children with acrodysostosis (ACRDYS).

Methods

This case series study enrolled 6 children with ACRDYS from Capital Center for Children's Hospital of Capital Institute of Pediatrics, Beijing Children's Hospital Affiliated of Capital Medical University, and the Second Affiliated Hospital of Guangxi Medical University. Diagnosis was confirmed by whole-exome sequencing between July 2023 and April 2026. Clinical data, laboratory findings, radiographic features, treatment details, and genetic test results were reviewed.

Results

Among the 6 ACRDYS children, 5 had PRKAR1A gene variation (ACRDYS1) and 1 had PDE4D gene variation (ACRDYS2). There were 3 boys and 3 girls. The age at diagnosis was 6.3 (5.3,9.1) years. Four children presented with short stature and 2 with short hands and feet. One child was born preterm, 1 was small for gestational age, and 1 had a positive family history. All 6 children had brachydactyly and characteristic facial features, including depressed nasal bridge, upturned nasal tip, long philtrum, and micrognathia. Two children were obese. The 4 children with ACRDYS1 had parathyroid hormone resistance and 3 had thyroid-stimulating hormone (TSH) resistance (1 child was not tested for TSH). The child with ACRDYS2 had mild intellectual developmental delay and no hormone resistance. Hand radiographs showed shortened metacarpals and phalanges with cone-shaped epiphyses in all patients. Bone age was advanced in 3 children and delayed in 1. Genetic testing showed PRKAR1A variants in 5 children and a PDE4D variant in 1 child. The PRKAR1A nonsense variant p.Arg368* was the most common, detected in 3 of the 5 children. One PDE4D variant was previously unreported.

Conclusions

Children with ACRDYS typically present with brachydactyly or brachytelephalangy, midfacial hypoplasia, and hand radiographic abnormalities. ACRDYS1 is often accompanied by mild hormone resistance, while ACRDYS2 features neurodevelopmental delay without obvious endocrine abnormalities.