Angelman Syndrome: Early Signs Recognition, Differentiation from Prader-Willi Syndrome, and the Role of UBE3A Genetic Testing in Severe Developmental Delay and Epileptic Seizures

The Angelman syndrome is a rare neurogenetic disorder characterized by severe developmental delay, epileptic seizures, and a distinctive behavioral phenotype that includes a happy and cheerful disposition. Early identification of this syndrome is crucial for implementing appropriate interventions and improving the quality of life for patients. However, its diagnosis can be complicated due to symptom overlap with other syndromes, such as Prader-Willi syndrome.

Early Signs Recognition

Early diagnosis of Angelman syndrome relies on the observation of characteristic clinical signs and confirmation through a UBE3A genetic test. Clinical signs include delays in motor and language development, ataxia, and an unusually happy demeanor. Epileptic seizures are common and typically begin in early childhood, which can be a key indicator for physicians.

In contrast, Prader-Willi syndrome initially presents with neonatal hypotonia and feeding difficulties, followed by excessive weight gain and behavioral issues. Although both syndromes share the chromosomal region 15q11-q13, their clinical and genetic manifestations are distinct, underscoring the importance of accurate differentiation.

Differentiation from Prader-Willi Syndrome

Differentiating between Angelman syndrome and Prader-Willi syndrome is essential for appropriate clinical management. While Angelman syndrome is associated with the loss of function of the UBE3A gene on the maternal chromosome, Prader-Willi syndrome results from the lack of expression of genes on the paternal chromosome. The DNA methylation analysis is a key diagnostic tool that can differentiate between these two syndromes by identifying the parental origin of genetic alterations.

Additionally, feeding behavior may provide further clues. While hyperphagia is a distinctive feature of Prader-Willi syndrome, it has also been observed in other neurogenetic disorders, which can complicate differential diagnosis in early childhood.

Conclusions

Early recognition and accurate differentiation of Angelman syndrome from Prader-Willi syndrome are fundamental for clinical management and treatment planning. Understanding the genetic and clinical differences between these syndromes enables physicians to implement more effective and personalized intervention strategies. Interdisciplinary collaboration and the use of advanced diagnostic tools, such as the UBE3A genetic test and DNA methylation analysis, are essential for improving outcomes in these patients.

Referencias

• [1] Specificity of Early Childhood Hyperphagia Profiles in Neurogenetic Conditions.
• [2] Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings.
• [3] The inv dup (15) or idic (15) syndrome (Tetrasomy 15q).

Created 13/1/2025