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Background Recurrent 15q13.3 microdeletions were recently identified with identical proximal (BP4) and distal (BP5) breakpoints and associated with mild to moderate mental retardation and epilepsy. Methods To further assess the clinical implications of this novel 15q13.3 microdeletion syndrome, eighteen new probands with a deletion were molecularly and clinically characterised. In addition, we evaluated the characteristics of a family with a more proximal deletion between BP3 and BP4. Finally, four patients with a duplication in the BP3-BP4-BP5 region were included in this study to ascertain the clinical significance of duplications in this region. Results The 15q13.3 microdeletion in our series was associated with a highly variable intra- and inter-familial phenotype. At least 11 of the 18 deletions identified were inherited. Moreover, 7 of 10 siblings from four different families also had this deletion: one had a mild developmental delay, four had only learning problems during childhood, but functioned well in daily life as adults, whereas the other two had no learning problems at all. In contrast to previous findings, seizures were not a common feature in our series (only 2 of 17 living probands). Three patients with deletions had cardiac defects and deletion of the KLF13 gene, located in the critical region, may contribute to these abnormalities. The limited data from the single family with the more proximal BP3-BP4 deletion suggest this deletion may have little clinical significance. Patients with duplications of the BP3-BP4-BP5 region did not share a recognizable phenotype, but psychiatric disease was noted in 2 of 4 patients. Conclusions Overall, our findings broaden the phenotypic spectrum associated with 15q13.3 deletions and suggest that, in some individuals, deletion of 15q13.3 is not sufficient to cause disease. The existence of microdeletion syndromes, associated with an unpredictable and variable phenotypic outcome, will pose the clinician with diagnostic difficulties and challenge the commonly used paradigm in the diagnostic setting that aberrations inherited from a phenotypically normal parent are usually without clinical consequences.

The aim of this review is to determine the relationship between gestational age (GA) and prevalence, type, distribution, and severity of cerebral palsy (CP). Epidemiological studies with cohorts expressed by GA were assessed. A comprehensive meta-analysis and metaregression was performed on four fetal age categories. Studies of children with CP as a target population were added. Twenty-six articles met the inclusion criteria. The prevalence of CP decreases significantly with increasing GA category: 14.6% at 22 to 27 weeks' gestation, 6.2% at 28 to 31 weeks, 0.7% at 32 to 36 weeks, and 0.1% in term infants. Interestingly, a significant decrease in prevalence of CP starts only from a GA of 27 weeks onwards. In preterm infants, spastic CP is predominant. In term infants, the non-spastic form of CP is more prevalent than in preterm infants. Bilateral spastic CP is most prevalent in both preterm and term infants. However, the proportion of unilateral spastic CP in term infants is substantial. No relationship could be detected between severity of CP and GA. There is a strong need for an international, well-described, and generally accepted classification system for subtypes and severity of CP.Cerebral palsy (CP) is one of the most common and well-recognized neurodevelopmental conditions, beginning in early childhood and persisting through the lifespan. 1 It is generally accepted that the risk of CP decreases with increasing gestational age (GA) of live-born infants. 2 Registers of childhood impairments and large population-based studies in Europe, [3][4][5][6][7][8] Japan, 9 and North America 10 monitored trends in rates of CP according to GA but focused mainly on the diagnosis of CP as a parameter reflecting the quality of perinatal care. Other studies were very fractionized and focused mostly on extremely and very preterm infants 11-22 but failed to present an overview of all age categories. In contrast, in these latter studies regarding extremely preterm infants, the presented prevalence rates of CP for each week of gestation are rather inconsistent and do not subscribe to the assumption that increasing GA results in decreasing rates of CP.In this meta-analysis we reveal the characteristics of the association between GA and CP. While exploring prevalence rates of CP in relation to GA, we found in several articles a link between GA and type and distribution of CP. Therefore, we looked for a relationship between GA and the characteristics of CP; specifically the type, distribution, and severity of CP. Method SEARCH STRATEGY AND STUDY SELECTIONTo explore the association between GA and the prevalence of

Objective: Congenital cytomegalovirus (cCMV) infection is the most common non-genetic cause of sensorineural hearing loss in children. Although cCMV-induced vestibular loss is demonstrated in several studies, the occurrence of vertigo has been described in only two cases to date. The aim of this paper is to discuss the underlying pathophysiology of recurrent vestibular symptoms in children with cCMV, based on five cases investigated in our center and an extensive research of the literature. Study Design: Retrospective case series. Setting: Tertiary referral center. Patients: This case series describes five pediatric cCMV-patients (three boys, two girls). Four of them were symptomatic at birth, one was asymptomatic. Three patients underwent cochlear implantation. The age of onset of the vestibular symptoms varied from 2;0 to 7;3 years of age. Intervention: None Main Outcome Measures: Details about the patient history and results of cranial imaging, audiological, vestibular and neurological assessments were collected retrospectively. Results: The selected cases suffered from recurrent vestibular symptoms. All patients had delayed onset, fluctuating and/or progressive hearing loss. In all cases, the attacks were accompanied with nausea and vomiting and occurred without clear-cut trigger. Migraine and epilepsy often were proposed as first diagnosis, although they could not be confirmed eventually. Four out of five patients were diagnosed with a peripheral vestibular deficit. 4 Conclusions: Diagnosis of vestibular symptoms in children with cCMV is complex, given the multiple morbidities than can occur. Peripheral vestibular causes should be considered in the diagnosis, as important vestibular deficits are demonstrated in this population.

Pathogenic variants in the RBM10 gene cause a rare X‐linked disorder described as TARP (Talipes equinovarus, Atrial septal defect, Robin sequence, and Persistent left vena cava superior) syndrome. We report two novel patients with truncating RBM10 variants in view of the literature, presenting a total of 26 patients from 15 unrelated families. Our results illustrate the highly pleiotropic nature of RBM10 pathogenic variants, beyond the classic TARP syndrome features. Major clinical characteristics include severe developmental delay, failure to thrive, brain malformations, neurological symptoms, respiratory issues, and facial dysmorphism. Minor features are growth retardation, cardiac, gastrointestinal, limb, and skeletal abnormalities. Additional recurrent features include genital and renal abnormalities as well as hearing and visual impairment. Thus, RBM10 loss of function variants typically cause an intellectual disability and congenital malformation syndrome that requires assessment of multiple organ systems at diagnosis and for which provided clinical features might simplify diagnostic assessment. Furthermore, evidence for an RBM10‐related genotype–phenotype correlation is emerging, which can be important for prognosis.