Abnormal breathing patterns are a typical feature of Rett and
Pitt-Hopkins syndrome and their variants. Their treatment can be challenging, with a risk of long-term detrimental consequences.
Early infantile epileptic encephalopathy (EIEE) type 54 is a rare epileptic
encephalopathy caused by pathogenic variants in the
heterogeneous nuclear ribonucleoprotein U (HNRNPU) gene. Only one case has been described in the literature with episodes of
hyperventilation and
apnea, but treatment was not discussed. We describe the clinical and genetic features and treatment strategies in a case of EIEE type 54 and severely abnormal breathing pattern. A novel and likely pathogenic c.2277dup, p.(Pro760Serfs*5) variant in the HNRNPU gene was found in a male patient with severe episodes of
hyperventilation and
apnea, leading to
syncope. Combination
therapy with
acetazolamide,
alprazolam and
aripiprazole led to significant clinical improvement. Although HNRNPU has not been implicated in breathing control, pathogenic variants in this gene can be associated with the development of abnormal breathing patterns reminiscent of Rett and
Pitt-Hopkins syndrome. Its function as a gene expression regulator and its interaction with
transcription factors offers a potential pathogenetic link between these 3 disorders. Based on our experience, treatment strategies can be similar to those already applied for patients with Pitt-Hopkins and
Rett syndrome.