Clonal Elimination of the Pathogenic Allele as Diagnostic Pitfall in SAMD9L-Associated Neuropathy.

BACKGROUND: Heterozygous gain-of-function variants in SAMD9L are associated with ataxia-pancytopenia syndrome (ATXPC) and monosomy 7 myelodysplasia and leukemia syndrome-1 (M7MLS1). Association with peripheral neuropathy has rarely been described. METHODS: Whole-exome sequencing (WES) from DNA extracted from peripheral blood was performed in a 10-year-old female presenting with demyelinating neuropathy, her similarly affected mother and the unaffected maternal grandparents. In addition to evaluation of single nucleotide variants, thorough work-up of copy number and exome-wide variant allele frequency data was performed. RESULTS: Combined analysis of the mother's and daughter's duo-exome data and analysis of the mother's and her parents' trio-exome data initially failed to detect a disease-associated variant. More detailed analysis revealed a copy number neutral loss of heterozygosity of 7q in the mother and led to reanalysis of the exome data for respective sequence variants. Here, a previously reported likely pathogenic variant in the SAMD9L gene on chromosome 7q (NM_152703.5:c.2956C>T; p.(Arg986Cys)) was identified that was not detected with standard filter settings because of a low percentage in blood cells (13%). The variant also showed up in the daughter at 32%, a proportion well below the expected 50%, which in each case can be explained by clonal selection processes in the blood due to this SAMD9L variant. CONCLUSION: The report highlights the specific pitfalls of molecular genetic analysis of SAMD9L and, furthermore, shows that gain-of-function variants in this gene can lead to a clinical picture associated with the leading symptom of peripheral neuropathy. Due to clonal hematopoietic selection, displacement of the mutant allele occurred, making diagnosis difficult.

[Orbital complication of acute sinusitis : Orbital cellulitis in a 10-year-old child]. / Orbitale Komplikation einer akuten Sinusitis : Orbitaphlegmone bei einem 10-jährigen Kind.

Bacterial orbital cellulitis is a life-threatening infection of the postseptal orbital tissue. It can occur in the context of sinusitis, particularly in children and adolescents. Ocular complications include exposure keratopathy, increased intraocular pressure, occlusion of the central retinal artery or vein and optic neuropathy. Rarely, a subperiosteal abscess can occur, and osteomyelitis can lead to spread of the infection to the cerebrum. A rapid diagnosis and targeted therapy are essential for saving the eye as well as the life of the patient.

[Quantum of luck with a self-induced penetrating orbital injury]. / Quäntchen Glück bei einer selbst induzierten penetrierenden Orbitaverletzung.

Presentation of a patient with two foreign bodies each 21 cm long in left nasal orbit and penetrating as far as the sinciput. The patient had been knitting at the time of the accident and had probably autonomously thrust the two knitting needles into the left orbit, as assessed by questioning of other parties. The patient had a known history of paranoid schizophrenia and dementia. Central imaging revealed the position of the knitting needles with respect to the intracranial vessels to be threatening. The surgical removal of the knitting needles was carried out without any serious complications, such as intracranial hemorrhage.

The Benefits of High Relaxivity for Brain Tumor Imaging: Results of a Multicenter Intraindividual Crossover Comparison of Gadobenate Dimeglumine with Gadoterate Meglumine (The BENEFIT Study).

BACKGROUND AND PURPOSE: Gadobenate dimeglumine (MultiHance) has higher r1 relaxivity than gadoterate meglumine (Dotarem) which may permit the use of lower doses for MR imaging applications. Our aim was to compare 0.1- and 0.05-mmol/kg body weight gadobenate with 0.1-mmol/kg body weight gadoterate for MR imaging assessment of brain tumors. MATERIALS AND METHODS: We performed crossover, intraindividual comparison of 0.1-mmol/kg gadobenate with 0.1-mmol/kg gadoterate (Arm 1) and 0.05-mmol/kg gadobenate with 0.1-mmol/kg gadoterate (Arm 2). Adult patients with suspected or known brain tumors were randomized to Arm 1 (70 patients) or Arm 2 (107 patients) and underwent 2 identical examinations at 1.5 T. The agents were injected in randomized-sequence order, and the 2 examinations were separated by 2-14 days. MR imaging scanners, imaging sequences (T1-weighted spin-echo and T1-weighted high-resolution gradient-echo), and acquisition timing were identical for the 2 examinations. Three blinded readers evaluated images for diagnostic information (degree of definition of lesion extent, lesion border delineation, visualization of lesion internal morphology, contrast enhancement) and quantitatively for percentage lesion enhancement and lesion-to-background ratio. Safety assessments were performed. RESULTS: In Arm 1, a highly significant superiority (P < .002) of 0.1-mmol/kg gadobenate was demonstrated by all readers for all end points. In Arm 2, no significant differences (P > .1) were observed for any reader and any end point, with the exception of percentage enhancement for reader 2 (P < .05) in favor of 0.05-mmol/kg gadobenate. Study agent-related adverse events were reported by 2/169 (1.2%) patients after gadobenate and by 5/175 (2.9%) patients after gadoterate. CONCLUSIONS: Significantly superior morphologic information and contrast enhancement are demonstrated on brain MR imaging with 0.1-mmol/kg gadobenate compared with 0.1-mmol/kg gadoterate. No meaningful differences were recorded between 0.05-mmol/kg gadobenate and 0.1-mmol/kg gadoterate.

Serious head injury in young children: birth trauma versus non-accidental head injury.

Birth injury of the skull and central nervous system can be a complication of a difficult delivery, especially following forceps or vacuum-assisted delivery. Birth trauma of the head can also mimic the appearance of a non-accidental head injury and is therefore an important differential diagnosis. We report on two young infants with serious head injuries. The difficult differential diagnosis birth trauma versus non-accidental head injury is discussed and the necessity for cooperation between clinicians, forensic doctors and specialized neuroradiologists is emphasized.

Neuron loss in the mouse hippocampus following prenatal injection of tritiated thymidine or saline.

To investigate possible effects of injections of tritiated thymidine ([3H]dThd) into pregnant mice or the injection procedure itself on the proliferation of neuronal precursor cells in the fetuses, pregnant mice received intraperitoneal injections of either [3H]dThd or saline on embryonic days 12, 14, and 19, while their offspring remained untreated. A second group of dams was not injected but their male offspring received a subcutaneous injection of again either [3H]dThd or saline on postnatal day 10. Then total numbers of hippocampal pyramidal cells (areas CA1 to CA3) and granular cells (dentate gyrus) were determined stereologically for 20-day-old as well as for 80-day-old male pups. No significant differences were found for the mean total number of pyramidal cells between the investigated groups of pups. However, the mean total number of granular cells was significantly reduced in those groups in which the dams had received an intraperitoneal injection, irrespective of whether [3H]dThd or saline was injected. This revives the repeated warning in the literature to consider the effect of the injection procedure on the developing brain when interpreting possible effects of agents administered during pregnancy.