A case of two sisters with classic symptoms of Angelman syndrome but no identifiable genetic mutation highlights the importance of proper diagnosis and care to improve the quality of life in this patient population.
Reported by Çelebi Kocaoğlu, MD, from the Konya Training and Research Hospital in Turkey, the study, “Two sisters with Angelman Syndrome: A case series report,” was published in the Journal of Pediatric Neurosciences.
At birth, the youngest sister had all evaluated parameters within normal ranges following an uneventful pregnancy and birth. By 6 months old, she started having eye problems (strabismus) and delayed physical development, and was only able to sit unsupported by 12 months old and to walk independently at 28 months old. During this period, she was still unable to speak.
The child started to experience tonic seizures by 30 months old, but no reports of treatment with anti-convulsant drugs were found. At 3 years old, she had an operation to correct an abnormal tissue growth in her hip.
At 5 years old, she was admitted to the clinic due to seizures with sudden muscle contractions caused by high fever. At this stage, she also had sleep disturbances, repetitive movements (stereotypies), and exhibited happy behavior with frequent and inappropriate smiling and laughter.
Physical examination showed she was smaller and thinner than expected for her age. Subtle facial features were also noted, including a large mouth, widely spaced teeth and deep-set eyes. She also had a marked line on her right hand.
Blood analysis did not reveal any significant alterations, with normal metabolic, hematologic, and biochemical profiles. Results from hearing tests were also within normal ranges, although she could not communicate. However, evaluation of brain activity with an electroencephalography (EEG) revealed significant changes.
Based on the clinical presentation, she was diagnosed with Angelman syndrome. She was started on treatment with Depakene (valproic acid) to control the seizures, and she was sent to a special school for students with disabilities.
Her older sister had a similar clinical history. Pregnancy and birth were also uneventful, but the girl had delayed physical development, with no capacity to verbalize words. By 7 months old, she experienced febrile seizures, which were controlled with anti-convulsive therapy.
She also exhibited a happy demeanor with inappropriate smiling and laughter, as well as hyperactive behavior. Clinical examination revealed dysmorphic facial features, including a wide mouth, spaced teeth and deep-set eyes.
Genetic testing was performed for both sisters, but no mutation related to the diagnosis was detected. “We consider that our patients were probably affected by a genetic defect we failed to determine,” Kocaoğlu wrote.
Despite no genetic proof of the disease, both sisters had the “classical manifestations of Angelman syndrome, including severe intellectual disability with major speech impairment,” he said.
The researcher believes that “even if 15q11-q13 deletion gene mutation [the hallmark of the disease] cannot be demonstrated, it should be kept in mind that different mutations may exist in the cases that are suggestive of clinical Angelman syndrome.”
An appropriate and timely diagnosis is of extreme importance as “patients with Angelman syndrome can be exposed to special education, and their quality of life can be elevated,” Kocaoğlu said.