Medical Genetic Service
Medical Genetic Service
Pini G.,Tuscany Rett Center Versilia Hospital |
Bigoni S.,Tuscany Rett Center Versilia Hospital |
Bigoni S.,University of Ferrara |
Engerstrom I.,Stersund Hospital |
And 24 more authors.
Neuropediatrics | Year: 2012
Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting almost exclusively females. The Hanefeld variant, or early-onset seizure variant, has been associated with mutations in CDKL5 gene. Aims In recent years more than 60 patients with mutations in the CDKL5 gene have been described in the literature, but the cardiorespiratory phenotype has not been reported. Our aim is to describe clinical and autonomic features of these girls. Methods 10 girls with CDKL5 mutations and a diagnosis of Hanefeld variant have been evaluated on axiological and clinical aspects. In all subjects an evaluation of the autonomic system was performed using the Neuroscope. Results Common features were gaze avoidance, repetitive head movements and hand stereotypies. The autonomic evaluation disclosed eight cases with the Forceful breather cardiorespiratory phenotype and two cases with the Apneustic breather phenotype. Conclusions The clinical picture remains within the RTT spectrum but some symptoms are more pronounced in addition to the very early onset of seizures. The cardiorespiratory phenotype was dominated by Forceful breathers, while Feeble breathers were not found, differently from the general Rett population, suggesting a specific behavioral and cardiorespiratory phenotype of the RTT the Hanefeld variant. Copyright © 2012 by Thieme Medical Publishers, Inc.
Migliore C.,Institute for Maternal and Child Health IRCCS Burlo Garofolo |
Athanasakis E.,Institute for Maternal and Child Health IRCCS Burlo Garofolo |
Dahoun S.,University of Geneva |
Wonkam A.,University of Cape Town |
And 11 more authors.
European Journal of Medical Genetics | Year: 2013
Opitz G/BBB Syndrome (OS) is a multiple congenital anomaly disorder characterized by developmental defects of midline structures. The most relevant clinical signs are ocular hypertelorism, hypospadias, cleft lip and palate, laryngo-tracheo-esophageal abnormalities, imperforate anus, and cardiac defects. Developmental delay, intellectual disability and brain abnormalities are also present. The X-linked form of this disorder is caused by mutations in the MID1 gene coding for a member of the tripartite motif family of E3 ubiquitin ligases. Here, we describe 12 novel patients that carry MID1 mutations emphasizing that laryngo-tracheo-esophageal defects are very common in OS patients and, together with hypertelorism and hypospadias, are the most frequent findings among the full spectrum of OS clinical manifestations. Besides missense and nonsense mutations, small insertions and deletions scattered along the entire length of the gene, we found that a consistent number of MID1 alterations are represented by the deletion of single coding exons. Deep characterization of one of these deletions reveals, for the first time within the MID1 gene, a complex rearrangement composed of two deletions, an inversion and a small insertion that may suggest the involvement of concurrent non-homologous mechanisms in the generation of the observed structural variant. © 2013 Elsevier Masson SAS.