Variant of Rett Syndrome and CDKL5 Gene: Clinical and Autonomic Description of 10 Cases

Pini, Giorgio; Bigoni, Stefania; Engerström, Ingegerd Witt; Calabrese, Olga; Felloni, Beatrice; Scusa, Maria Flora; Marco, Pietro Di; Borelli, Paolo; Bonuccelli, Ubaldo; Julu, Peter O.O.; Nielsen, Jan Kresten; Morin, Bodil; Hansen, Stig; Gobbi, Giuseppe; Visconti, Paola; Pintaudi, Maria; Veneselli, E.; Romanelli, Anna Maria; Bianchi, Fabrizio; Casarano, Manuela; Battini, Roberta; Cioni, Giovanni; Ariani, Francesca; Renieri, Alessandra; Benincasa, Alberto; Delamont, Robert S.; Zappella, Michele

doi:10.1055/s-0032-1308856

Cited by 31 publications

(33 citation statements)

References 23 publications

(22 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The presence of hyperventilation was mentioned in only one of the first clinical surveys 5 . A recent study in 10 patients with CDKL5 mutations demonstrated the presence of cardiorespiratory dysrhythmias such as tachypnoea (11.7%), deep breathing (4%), and apnoeas (1.4%) and breath holding (3.25%) 9 …”

Section: Discussionmentioning

confidence: 99%

Respiratory and sleep disorders in female children with atypical Rett syndrome caused by mutations in the CDKL5 gene

Hagebeuk

Bossche

Weerd

2012

Develop Med Child Neuro

View full text Add to dashboard Cite

AIM In female children with drug-resistant seizures and developmental delay from birth, atypical Rett syndrome caused by mutations in the CDKL5 gene should be considered. Several clinical features resemble classic Rett syndrome. Respiratory and sleep abnormalities are frequently present in Rett syndrome, whereas little is known in patients with CDKL5 mutations.METHOD In four genetically confirmed female patients with CDKL5 mutations (age range 2-15y), the presence of breathing and sleep abnormalities was evaluated using the validated Sleep Disturbance Scale for Children and polysomnography (PSG). RESULTSThe Sleep Disturbance Scale for Children indicated disorders of initiating and maintaining sleep, daytime somnolence, and sleep breathing disorders. In one patient, PSG showed central apnoeas during sleep: her total apnoea-hypopnoea index (AHI) was 4.9, of which the central AHI was 3.4 ⁄ h. When awake, central apnoeas were present in two of the four female children (central AHI 28 ⁄ h and 41 ⁄ h respectively), all preceded by hyperventilation. PSG showed low rapid eye movement (REM) sleep (9.7-18.3%), frequent awakenings, and low sleep efficiency (range 59-78%).INTERPRETATION Episodic hyperventilation followed by central apnoeas was present while awake in two of four patients. This may indicate failure of brainstem respiratory centres. In addition, low REM sleep, frequent arousals (not caused by apnoeas ⁄ seizures), and low sleep efficiency were present. Similar to Rett syndrome, in patients with CDKL5 mutations PSG seems warranted to evaluate breathing and sleep disturbances.

show abstract

Section: Discussionmentioning

confidence: 99%

Respiratory and sleep disorders in female children with atypical Rett syndrome caused by mutations in the CDKL5 gene

Hagebeuk

Bossche

Weerd

2012

Develop Med Child Neuro

View full text Add to dashboard Cite

show abstract

“…Most studies of the CDKL5 disorder have been limited to case studies or small case series and while functional abilities have mostly been described as severely impaired [White et al, ; Liang et al, ; Olson and Poduri, ; Fehr et al, ; Hagebeuk et al, ], variability in the clinical features has also been reported. It appears that some individuals are less severely affected, in terms of motor abilities and are able to walk [Weaving et al, ; Martínez et al, ; Pini et al, ] and even run [Bartnik et al, ]. Expressive communication seems to be mostly limited to vocalizations and babble [Tao et al, ; Evans et al, ; Nemos et al, ; Artuso et al, ; Jähn et al, ], although some girls are able to use words in phrases [Weaving et al, ; Archer et al, ; Martínez et al, ].…”

Section: Introductionmentioning

confidence: 99%

“…Expressive communication seems to be mostly limited to vocalizations and babble [Tao et al, ; Evans et al, ; Nemos et al, ; Artuso et al, ; Jähn et al, ], although some girls are able to use words in phrases [Weaving et al, ; Archer et al, ; Martínez et al, ]. Hand function has been less well documented [Bahi‐Buisson et al, ; Bartnik et al, ; Martínez et al, ; Olson and Poduri, ; Hagebeuk et al, ; Pini et al, ], but would appear to be absent or limited for most [Tao et al, ; Evans et al, ; Nemos et al, ; Artuso et al, ; Jähn et al, ].…”

Section: Introductionmentioning

confidence: 99%

Functional abilities in children and adults with the CDKL5 disorder

Fehr

Downs

et al. 2016

American J of Med Genetics Pt A

103

View full text Add to dashboard Cite

Functional abilities in the CDKL5 disorder have been described as severely impaired, yet some individuals are able to run and use phrases for speech. Our study investigated gross motor, hand function, and expressive communication abilities in individuals with the CDKL5 disorder. Data for 108 females and 16 males registered with the International CDKL5 disorder database and with a pathogenic CDKL5 mutation were analyzed. Relationships between functional abilities, age, genotype, and gender were analyzed using regression models. Over half of the females could sit on the floor and nearly a quarter could walk 10 steps. Fewer males could complete these tasks although one boy was able to sit, walk, and run. Most females and few males were able to pick up a large object. Females mostly used gestures to communicate while males mostly used other forms of non-verbal communication. Compared to those with no functional CDKL5 protein, individuals with truncating variants after aa 781 were more likely to be able to stand (OR 5.7, 95%CI 1.2, 26.6) or walk independently (4.3, 95%CI 0.9, 20.5), and use more advanced communication methods such as words (OR 6.1, 95%CI 1.5-24.2). Although abilities were markedly impaired for the majority with the CDKL5 disorder, some females and a few males had better functional abilities. This variability may be related to underlying gene variants, with females with a late truncating variant having better levels of ability than those with no functional protein. © 2016 Wiley Periodicals, Inc.

show abstract

“…Similar abnormalities occur in MeCP2 knockout (KO) mice in which the respiratory phenotype worsens with time, leading eventually to death (Ren et al ., ; Stettner et al ., ). Due to the recent discovery and rarity of the CDKL5 disorder, evidence concerning sleep‐disordered breathing in CDKL5 disease is limited (Hagebeuk et al ., ; Pini et al ., ), and lacking altogether in adults. The development of Cdkl5‐KO mice (Amendola et al ., ) may accelerate understanding of the pathophysiology of this disease, with the goal of promoting therapeutic developments.…”

Section: Introductionmentioning

confidence: 99%

CDKL5 deficiency entails sleep apneas in mice

Martire

Alvente

Bastianini

et al. 2017

Journal of Sleep Research

View full text Add to dashboard Cite

A recently discovered neurodevelopmental disorder caused by the mutation of the cyclin-dependent kinase-like 5 gene (CDKL5) entails complex autistic-like behaviours similar to Rett syndrome, but its impact upon physiological functions remains largely unexplored. Sleep-disordered breathing is common and potentially life-threatening in patients with Rett syndrome; however, evidence is limited in children with CDKL5 disorder, and is lacking altogether in adults. The aim of this study was to test whether the breathing pattern during sleep differs between adult Cdkl5 knockout (Cdkl5-KO) and wild-type (WT) mice. Using whole-body plethysmography, sleep and breathing were recorded non-invasively for 8 h during the light period. Sleep apneas occurred more frequently in Cdkl5-KO than in WT mice. A receiver operating characteristic (ROC) analysis discriminated Cdkl5-KO significantly from WT mice based on sleep apnea occurrence. These data demonstrate that sleep apneas are a core feature of CDKL5 disorder and a respiratory biomarker of CDKL5 deficiency in mice, and suggest that sleep-disordered breathing should be evaluated routinely in CDKL5 patients.

show abstract

Variant of Rett Syndrome and CDKL5 Gene: Clinical and Autonomic Description of 10 Cases

Cited by 31 publications

References 23 publications

Respiratory and sleep disorders in female children with atypical Rett syndrome caused by mutations in the CDKL5 gene

Respiratory and sleep disorders in female children with atypical Rett syndrome caused by mutations in the CDKL5 gene

Functional abilities in children and adults with the CDKL5 disorder

CDKL5 deficiency entails sleep apneas in mice

Contact Info

Product

Resources

About