Intranasal insulin may influence motor activities and behaviour in Phelan McDermid Syndrom

Aims: Phelan McDermid syndrome (22q13.3 deletion syndrome) creates from a terminal deletion of the long arm of chromosome 22 giving rise dysfunction of the SHANK3 gene. Common features are hypotonia, global developmental delay (DD) and highly impaired or even absent speech. In the majority no characteric dysmorphic appearence nor growth anomalies are found. Encouraged by the effects of intranasal insulin reported by Schmidt et al (JMG, 2009) we were interested to look for such improvements in an own patient.

Methods: 9 years old girl of Somalian descent, history of muscular hypotonia, accelerated growth, severe global developmental delay and absent expressive language. She showed an autistic behaviour, motor restlessness, missing eye contact and self-stimulatory behaviour (flapping hands, persistent chewing, rocking). Karyotype was normal, but subtelomer screening by MLPA revealed a microdeletion on 22q13 which was narrowed down to approximately 150 kb by FISH analysis, thus confirming an intragenic SHANK 3 deletion.

Treatment: intranasal insulin shots released from a nasal atomizer were gradually increased until the final dosage of 1.5 IU/kg/day, without any hypoglycemic episode.

Results: So far, we stated marked short- and long- term effects in cognitive function, nonverbal communication and autonomy. No side effects have been observed.

Conclusion: 22q13.3 deletion syndrome may easily overlooked due to lack of an obviously dysmorphic aspect, but should be considered in all cases of severe neonatal hypotonia associated with DD and absent speech and peculiar behaviour. The mechanism behind the observed insulin effect is still unknown. Insulin might be able to compensate partially SHANK3 protein dysfunction enhancing synaptic plasticity. Further studies are needed to substantiate the hypothesis of a long-lasting improvement.

Phelan McDermid syndrome - 22q13.3 deletion syndrome - intranasal insulin