A novel FBXO28 frameshift mutation in a child with developmental delay, dysmorphic features, and intractable epilepsy: A second gene that may contribute to the 1q41-q42 deletion phenotype.

Chromosome 1q41-q42 deletions have recently been associated with a recognizable neurodevelopmental syndrome of early childhood (OMIM 612530). Within this group, a predominant phenotype of developmental delay (DD), intellectual disability (ID), epilepsy, distinct dysmorphology, and brain anomalies on magnetic resonance imaging/computed tomography has emerged. Previous reports of patients with de novo deletions at 1q41-q42 have led to the identification of an evolving smallest region of overlap which has included several potentially causal genes including DISP1, TP53BP2, and FBXO28. In a recent report, a cohort of patients with de novo mutations in WDR26 was described that shared many of the clinical features originally described in the 1q41-q42 microdeletion syndrome (MDS). Here, we describe a novel germline FBXO28 frameshift mutation in a 3-year-old girl with intractable epilepsy, ID, DD, and other features which overlap those of the 1q41-q42 MDS. Through a familial whole-exome sequencing study, we identified a de novo FBXO28 c.972_973delACinsG (p.Arg325GlufsX3) frameshift mutation in the proband. The frameshift and resulting premature nonsense mutation have not been reported in any genomic database. This child does not have a large 1q41-q42 deletion, nor does she harbor a WDR26 mutation. Our case joins a previously reported patient also in whom FBXO28 was affected but WDR26 was not. These findings support the idea that FBXO28 is a monogenic disease gene and contributes to the complex neurodevelopmental phenotype of the 1q41-q42 gene deletion syndrome.

Gait analysis of teenagers and young adults diagnosed with autism and severe verbal communication disorders.

Both movement differences and disorders are common within autism spectrum disorders (ASD). These differences have wide and heterogeneous variability among different ages and sub-groups all diagnosed with ASD. Gait was studied in a more homogeneously identified group of nine teenagers and young adults who scored as "severe" in both measures of verbal communication and overall rating of Autism on the Childhood Autism Rating Scales (CARS). The ASD individuals were compared to a group of typically developing university undergraduates of similar ages. All participants walked a distance of 6-meters across a GAITRite (GR) electronic walkway for six trials. The ASD and comparison groups differed widely on many spatiotemporal aspects of gait including: step and stride length, foot positioning, cadence, velocity, step time, gait cycle time, swing time, stance time, and single and double support time. Moreover, the two groups differed in the percentage of the total gait cycle in each of these phases. The qualitative rating of "Body Use" on the CARS also indicated severe levels of unusual body movement for all of the ASD participants. These findings demonstrate that older teens and young adults with "severe" forms of Verbal Communication Impairments and Autism differ widely in their gait from typically developing individuals. The differences found in the current investigation are far more pronounced compared to previous findings with younger and/or less severely involved individuals diagnosed with ASD as compared to typically developing controls. As such, these data may be a useful anchor-point in understanding the trajectory of development of gait specifically and motor functions generally.

Two-legged hopping in autism spectrum disorders.

Sensory processing deficits are common within autism spectrum disorders (ASD). Deficits have a heterogeneous dispersion across the spectrum and multimodal processing tasks are thought to magnify integration difficulties. Two-legged hopping in place in sync with an auditory cue (2.3, 3.0 Hz) was studied in a group of six individuals with expressive language impaired ASD (ELI-ASD) and an age-matched control group. Vertical ground reaction force data were collected and discrete Fourier transforms were utilized to determine dominant hopping cadence. Effective leg stiffness was computed through a mass-spring model representation. The ELI-ASD group were unsuccessful in matching their hopping cadence (2.21 ± 0.30 hops·s(-1), 2.35 ± 0.41 hops·s(-1)) to either auditory cue with greater deviations at the 3.0 Hz cue. In contrast, the control group was able to match hopping cadence (2.35 ± 0.06 hops·s(-1), 3.02 ± 0.10 hops·s(-1)) to either cue via an adjustment of effective leg stiffness. The ELI-ASD group demonstrated a varied response with an interquartile range (IQR) in excess of 0.5 hops·s(-1) as compared to the control group with an IQR < 0.03 hops·s(-1). Several sensorimotor mechanisms could explain the inability of participants with ELI-ASD to modulate motor output to match an external auditory cue. These results suggest that a multimodal gross motor task can (1) discriminate performance among a group of individuals with severe autism, and (2) could be a useful quantitative tool for evaluating motor performance in individuals with ASD individuals.

Heart for bonding: a new protocol of care for hypoplastic left heart syndrome.

There are significant challenges involved in the perinatal and postnatal care of an infant with hypoplastic left heart syndrome (HLHS) and the infant's family. In the blink of an eye, the perfect child is lost, and a fragile infant is about to join the family. This case study and discussion is an overview of HLHS , a family's desire to make the birth of their infant normal, and how that desire initiated a change in philosophy and practice in our neonatal intensive care unit.