A new mutation has been discovered in the MECP2 gene – associated with most cases of Rett syndrome – in a toddler with clinical features suggestive of congenital variant-type Rett syndrome, one of the most severe atypical forms of the disease.
The child had hypercapnia, or high levels of carbon dioxide in her blood, but this only happened when she was sleeping, according to the case report. The researchers noted that these high levels were not caused by obstructive sleep apnea, a condition characterized by repeated obstruction of the airways during sleep.
“Such findings have never been reported before in a child with Rett syndrome,” the researchers wrote, describing “the ventilatory and clinical management of this unique case.”
Additionally, the team suggested screening patients with congenital-like Rett syndrome via carbon dioxide and oxygen monitoring at bedtime.
The report, “Sleep hypoventilation and hypercapnia in a case of congenital variant Rett syndromewas published in the Italian Journal of Pediatrics.
New mutation discovered in the MECP2 gene
Rett syndrome, which almost exclusively affects girls, is characterized by neurological and motor disorders that occur between 6 and 18 months.
Atypical forms of Rett syndrome occur when all of Rett’s diagnostic criteria are not met.
There are several subtypes of atypical Rett, some milder and others more severe than classic Rett syndrome. The most severe atypical form is congenital Rett syndrome, also known as Rolando variant, which is caused by mutations in the FOXG1 embarrassed. Notably, however, some clinicians now consider this condition to be a separate entity called FOXG1 syndrome.
While classic Rett causes breathing problems, particularly when patients are awake, it is unclear whether this symptom occurs in patients with atypical forms of the disease.
In this study, Italian researchers described the case of a 20-month-old girl with symptoms of congenital Rett syndrome. She had breathing problems that occurred exclusively during periods of sleep.
The child was born with low muscle tone, called hypotonia, but most tests came back normal. This included testing for Angelman syndrome and Prader-Willi syndrome, two genetic conditions.
At the age of 10 months, the girl showed a delay in motor skills. She could not properly control her head or grasp objects. She fixed her gaze just for up to three minutes. His height and head circumference were also below average for a child of his age. Over the following months, his muscle tone worsened.
Using next-generation sequencing (NGS) – a genetic test that allows the sequencing of multiple genes – the team identified a Again variant in the MECP2 gene that had never been reported before.
Still mutations occur during embryonic development and are not inherited. The MECP2 The gene provides instructions for a protein of the same name, which is important in regulating gene activity.
According to the researchers, this child “has a mutation encoding a stop codon with a probable profound alteration of protein function. This type of mutation corresponds to the particularly severe clinical picture of the patient.
A stop codon is a specific DNA sequence that essentially stops protein production in a cell.
“As our patient has the full clinical presentation of Rolando’s variant, we consider her to have congenital variant-like Rett syndrome,” the team wrote.
The team recommends testing similar patients
An x-ray taken after the genetic analysis confirmed that the toddler had extremely early scoliosis, an abnormal lateral curvature of the spine.
While sleeping, she also experienced hypoventilation – slow or shallow breathing that causes the body’s level of carbon dioxide to rise – and periodic breathing. This was defined as pauses in breathing lasting longer than three seconds separated by less than 20 seconds of normal breathing. At night, his oxygen saturation levels would drop below 90%, which is considered low.
The child did not have obstructive sleep apnea, defined as the absence of nasal airflow with continuous chest movements for two or more breaths. In addition, pulse oximetry – a test that measures the level of oxygen in the blood – and capnography, which measures the partial pressure of carbon dioxide in the airways, were normal when she was awake.
She was put on non-invasive ventilation (NIV) to help her breathe during bedtime. After optimization of the system, a slight improvement in muscle tone and social interactions with his caregiver were observed.
Further assessments, including polysomnography – a sleep study that records brain waves, blood oxygen levels, heart rate and breathing – will be done after four months and every six months thereafter. the team said.
“To our knowledge, this is the first case report [low oxygen blood levels] and persistent hypercapnia during sleep in a patient with a congenital form of [Rett syndrome]“, wrote the researchers.
The team urged clinicians to be proactive in screening for other patients with this variant.
“This unique case suggests the need for a very early polygraph or at least pulse oximetry plus capnography in every patient with the congenital variant of Rett syndrome. Generally speaking, we suggest to consider NGS techniques to reach delicate diagnosis such as Rett syndrome with congenital features in hypotonic patients,” they concluded.
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