Severe Central Breathing Disorder in Infant Boys: Think of Male Rett Syndrome

Background: The X-linked classic Rett syndrome due to MECP2 mutations occurs mainly in girls. Males carrying a single copy of MECP2 with a pathogenic variant are usually more severely affected. We report on four patients with neonatal-onset phenotype.

Case Reports: The four boys were born at term after uneventful pregnancies. Three of four newborns needed either respiratory support in the first minutes of life or showed low oxygenation after 10 minutes of life. Feeding problems and muscular hypotonia were reported already in the first weeks of life. Bradypnea on bedside monitor was observed in all patients, age at manifestation ranged from few days to 2 years.

In one patient polysomnography unmasked a severe central disordered breathing pattern with periodic breathing (80% of total sleep time, apnea hypopnea 201 per hour) and hypoventilation (mean: tcCO2 8.5 kPa) during wakefulness and sleep.

Severe developmental delay was found early. In two boys refractory epilepsy occurred. MRI revealed cerebral atrophy in one patient. Recurrent respiratory infections were common. 3 boys died at the age from 4 months to 4 years due to respiratory failure.

Diagnosis of male Rett syndrome was made in all after confirmation of different pathogenic variants in the MECP2-gene. In two patients, male Rett syndrome was clinically suspected. In one patient a neuromuscular disease was primarily considered due to severe muscular hypotonia.

Conclusion: The clinical picture of severe neonatal encephalopathy (OMIM # 200673) with severe central disordered breathing should prompt clinical suspicion of Rett syndrome in boys.

Publication History

Article published online:
28 October 2021