Atypical presentation of Angelman syndrome with intact expressive language due to low-level mosaicism

Abstract

Background: Angelman syndrome (AS) occurs due to a lack of expression or function of the maternally inherited UBE3A gene. Individuals with AS typically have significant developmental delay, severe speech impairment with absent to minimal verbal language, gait abnormalities including ataxia, and an incongruous happy demeanor. The majority of individuals with AS also have seizures and microcephaly. Some individuals with mosaic AS have been reported to have expressive language and milder levels of developmental delay.

Case report: We report a male patient presenting with mild to moderate intellectual disability, hyperphagia, obesity, and the ability to communicate verbally. His phenotype was suggestive of Prader-Willi syndrome. However, methylation testing was positive for Angelman syndrome and additional methylation specific multiplex ligation-dependent amplification (MS-MLPA) study revealed low-level mosaicism for AS.

Conclusion: A broader phenotypic spectrum should be considered for AS as patients with atypical presentations may otherwise elude diagnosis.

Keywords: Angelman syndrome; MS-MLPA; case report; expressive language; mosaicism.

FIGURE 1

Photograph of patient with low‐level mosaic Angelman syndrome.

FIGURE 2

MS‐MLPA detects paternal uniparental Disomy 15/imprinting defect low‐level mosaic. (a) Probe height ratio pattern after ligation reaction only. It showed two copies of PWS/AS alleles. (b) Probe height ratio pattern after both ligation and restriction digestion reactions. The black arrows indicate methylation specific probes. The results showed these loci were mostly unmethylated, but in mosaic status (did not reach “0”). bps: Base pair size.