Prolidase deficiency (PD) is a rare inborn error of metabolism causing ulcers and other skin disorders, splenomegaly, developmental delay, and recurrent infections. Most of the literature is constituted of isolated case reports. It occurs due to the mutations in the prolidase gene ( PEPD ) that result in loss of prolidase activity. We reported here a child who had presented with features compatible with hyper-immunoglobulin E syndrome (HIES) like recurrent skin ulcers, recurrent infections, facial dysmorphism, retained primary teeth, and elevated levels of immunoglobulin E levels but with normal flow cytometric assays, which was later diagnosed as PD.

Intellectual disability (ID) is considered a common neuropsychiatric disorder that affects up to 3% of the population. The etiologic origin of ID may be genetic, environmental, and multifactorial. Chromosomopathies are relatively common among the genetic causes of ID, especially in the most severe cases and those associated with dysmorphic features. Currently, the application of new molecular cytogenetics technologies has increasingly allowed the identification of microdeletions, microduplications, and unbalanced translocations as causes of ID. The objective of this study was to investigate the etiology of ID in patients admitted to a public hospital in Northeastern Brazil. In total, 119 patients with ID who had normal karyotypes and fragile X exams participated in this study. The patients were initially physically examined for microdeletion syndromes and then tested using fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), methylation-sensitive polymerase chain reaction (MS-PCR), and chromosome microarray analysis (CMA), according to clinical suspicion. Patients with no diagnoses after FISH, MLPA, and/or MS-PCR evaluations were subsequently tested by CMA. The rate of etiologic diagnoses of ID in the current study was 28%. FISH diagnosed 25 out of 79 tested (31%), MLPA diagnosed 26 out of 79 tested (32%), MS-PCR diagnosed 7 out of 20 tested (35%), and the single nucleotide polymorphism array diagnosed 6 out of 27 tested (22%). Although the CMA is the most complete and recommended tool for the diagnosis of microdeletions, microduplications, and unbalance translocations in patients with ID, FISH, MLPA, and MS-PCR testing can be used as the first tests for specific syndromes, as long as the patients are first physically screened clinically, especially in the public health networks system in Brazil, where resources are scarce.

Ion channels mediate voltage fluxes or action potentials that are central to the functioning of excitable cells such as neurons. The KCNB family of voltage-gated potassium channels (Kv) consists of two members (KCNB1 and KCNB2) encoded by KCNB1 and KCNB2, respectively. These channels are major contributors to delayed rectifier potassium currents arising from the neuronal soma which modulate overall excitability of neurons. In this study, we identified several mono-allelic pathogenic missense variants in KCNB2, in individuals with a neurodevelopmental syndrome with epilepsy and autism in some individuals. Recurrent dysmorphisms included a broad forehead, synophrys, and digital anomalies. Additionally, we selected three variants where genetic transmission has not been assessed, from two epilepsy studies, for inclusion in our experiments. We characterized channel properties of these variants by expressing them in oocytes of Xenopus laevis and conducting cut-open oocyte voltage clamp electrophysiology. Our datasets indicate no significant change in absolute conductance and conductance-voltage relationships of most disease variants as compared to wild type (WT), when expressed either alone or co-expressed with WT-KCNB2. However, variants c.1141A>G (p.Thr381Ala) and c.641C>T (p.Thr214Met) show complete abrogation of currents when expressed alone with the former exhibiting a left shift in activation midpoint when expressed alone or with WT-KCNB2. The variants we studied, nevertheless, show collective features of increased inactivation shifted to hyperpolarized potentials. We suggest that the effects of the variants on channel inactivation result in hyper-excitability of neurons, which contributes to disease manifestations.

BACKGROUND: The main complication of percutaneous iliosacral screw fixation is implant malposition, which can lead to vascular and nerve damage. The anatomical variability of the sacrum can make screw insertion difficult under fluoroscopic guidance. Among the methods described to improve the accuracy of this technique, stands out the use of computed tomography (CT). The aim of this study is to compare the results of iliosacral screw insertion with fluoroscopy or CT navigation.
METHODS: Retrospective cohort study of 66 iliosacral screws in 56 patients during 11 years. The screws were inserted with fluoroscopy in the operating room or with CT in the radiodiagnosis area. We collected data on patient characteristics, lesions, treatment, and clinical and radiological results.
RESULTS: Forty-seven screws were inserted with fluoroscopy and 19 with CT. A percentage of 18.2 of screws perforated the S1 osseous corridor. All of them were inserted with fluoroscopy guidance (0 vs. 34%; p<0.01). Those operated with CT accumulated more sacral dysmorphism criteria than those operated with fluoroscopy (2.2 vs. 1.6; p=0.02). The S1 corridor on the axial CT view was narrower in those in whom perforation had occurred (18.8 vs. 21.0mm; p=0.02). Two cases with perforation developed S1 radiculalgia. Two endopelvic screws had to be removed.
CONCLUSIONS: We advise the use of CT guidance for iliosacral screw insertion in patients with sacral dysmorphism or narrow S1 corridors in facilities where other navigation methods are not available.

CHD3 heterozygous variants are associated with Snijders Blok-Campeau syndrome (SBCS) which consists of intellectual disability (ID), macrocephaly, and dysmorphic facies. Most reported variants are missense or loss of function clustered within the ATPase/helicase domain of the protein. We report a severe neurocognitive phenotype caused by biallelic CHD3 variants in two siblings, each inherited from a mildly affected parent. Male and female siblings were referred to the Genetics Clinic due to severe ID and profound dysmorphism. The parents are first cousins of Iranian descent with borderline intellectual abilities. Exome sequencing was performed for the affected female and her parents. A single homozygous candidate variant in the CHD3 gene was detected in the proband: c.5384_5389dup. p.Arg1796_Phe1797insTrpArg, resulting in an in-frame insertion of 2 amino acids located outside the ATPase/helicase domain at the C-terminal region of CHD3-encoding residues. This variant is classified as likely pathogenic according to ACMG guidelines. The variant was detected in a heterozygous state in each parent. Both affected siblings were homozygous, while their unaffected brother did not carry the variant. Biallelic CHD3 variants cause a severe neurodevelopmental syndrome that is distinguishable from SBCS. We assume that the variant type (in-frame insertion) and location may enable CHD3 biallelic variants.

BACKGROUND: Sacral dysmorphism has been previously reported to occur in 30 % to 40 % of adult patients. It has been described by 6 widely accepted parameters on outlet x-ray views of the pelvis: steep alar slope, retained S1-S2 disk, presence of mamillary bodies, sacralized L5, tongue in groove SI joint, and non-round neural foramina. Studies have focused on the importance of identifying dysmorphism for safe treatment of fractures in pelvises with dysmorphic upper sacral segments. Less is known regarding whether dysmorphism may be protective against trauma. To our knowledge no studies have focused on how dysmorphic sacrums fracture compared to non-dysmorphic (ND) sacrums, and whether operative rates are different.
OBJECTIVE: To assess the rate of operative fixation of sacral fractures between pelvises with dysmorphic and ND sacrums, as well as whether a difference exists in fracture morphology between groups.
METHODS: This is a retrospective cohort study out of a single level 1 trauma center. Study participants consisted of those sustaining a pelvic ring injury who were 18 years or older in which orthopaedics was consulted, had CT imaging available, and did not have isolated acetabulum fractures. 355 subjects were included of 671 reviewed pelvic ring injuries. Sacrums were deemed dysmorphic if they met at least one of the six dysmorphic features, and it was determined whether they underwent operative intervention. Fracture classifications and patterning were identified on CT imaging. P values were set <0.05.
RESULTS: We found that 44 % of inclusions had a dysmorphic sacrum with the most common feature to be a steep alar slope (68 %). 17.17 % of subjects with a ND sacrum underwent treatment versus 16.56 % for dysmorphic sacrums. No statistical difference regarding operative fixation rates was uncovered (p = .879). However, we found a difference in fracture patterns regarding ipsilateral posterior SI joint widening (p = 0.020).
CONCLUSIONS: Our study suggests that sacral dysmorphism is not protective against operative fixation based on no difference in operative rates between groups. However, our data supports that pelvises with dysmorphic sacrums may fracture differently based on the difference observed regarding other pelvic ring injuries.

BACKGROUND: The main complication of percutaneous iliosacral screw fixation is implant malposition, which can lead to vascular and nerve damage. The anatomical variability of the sacrum can make screw insertion difficult under fluoroscopic guidance. Among the methods described to improve the accuracy of this technique, stands out the use of computed tomography (CT). The aim of this study is to compare the results of iliosacral screw insertion with fluoroscopy or CT navigation.
METHODS: Retrospective cohort study of 66 iliosacral screws in 56 patients during 11 years. The screws were inserted with fluoroscopy in the operating room or with CT in the radiodiagnosis area. We collected data on patient characteristics, lesions, treatment, and clinical and radiological results.
RESULTS: Forty-seven screws were inserted with fluoroscopy and 19 with CT. A percentage of 18.2 of screws perforated the S1 osseous corridor. All of them were inserted with fluoroscopy guidance (0 vs. 34%; p<0.01). Those operated with CT accumulated more sacral dysmorphism criteria than those operated with fluoroscopy (2.2 vs. 1.6; p=0.02). The S1 corridor on the axial CT view was narrower in those in whom perforation had occurred (18.8 vs. 21.0mm; p=0.02). Two cases with perforation developed S1 radiculalgia. Two endopelvic screws had to be removed.
CONCLUSIONS: We advise the use of CT guidance for iliosacral screw insertion in patients with sacral dysmorphism or narrow S1 corridors in facilities where other navigation methods are not available.

Multiple studies suggest an association between DLG2 and neurodevelopmental disorders and indicate the haploinsufficiency of this gene; however, few cases have been thoroughly described. We performed additional studies to confirm this clinical association and DLG2 haploinsufficiency.
Chromosomal microarray analysis was performed on 11,107 patients at the Cytogenetics Laboratory at the University of Alabama at Birmingham. The Database of Genomic Variants-Gold Standard Variants and the Genome Aggregation Database were selected for the association analysis. Fifty-nine patients from the literature and DECIPHER, all having DLG2 intragenic deletions, were included for comprehensive analysis of the distribution of these deletions.
A total of 13 patients with DLG2 intragenic deletions, from 10 families in our cohort, were identified. Nine of 10 probands presented with clinical features of neurodevelopmental disorders. Congenital anomalies and dysmorphism were common in our cohort of patients. Association analysis showed that the frequency of DLG2 deletions in our cohort is significantly higher than those in the Database of Genomic Variants-Gold Standard Variants and the Genome Aggregation Database. Most of DLG2 intragenic deletions identified in 69 unrelated patients from our cohort, the literature, and DECIPHER map to the 5\' region of the gene, with a hotspot centered around HPin7, exon 8, and HPin8.
Our findings reinforce the link between DLG2 intragenic deletions and neurodevelopmental disorders, strongly support the haploinsufficiency of this gene, and indicate that these deletions might also have an association with congenital anomalies and dysmorphism.

To investigate the structural bases of human oocytes\' cytoplasmic abnormalities and the causative mechanism of their emergence. Knowledge of an abnormal oocyte\'s intracellular organization is vital to establishing reliable criteria for clinical evaluation of oocyte morphology.
Laboratory-based study on experimental material provided by a private assisted reproduction clinic.
University laboratory and imaging center.
A total of 105 women undergoing hormonal stimulation for in vitro fertilization (IVF) donated their spare oocytes for this study.
Transmission electron microscopy (TEM) was used to analyze the fine morphology of 22 dysmorphic IVF oocytes exhibiting different types of cytoplasmic irregularities, namely, refractile bodies; centrally located cytoplasmic granularity (CLCG); smooth endoplasmic reticulum (SER) disc; and vacuoles. A total of 133 immature oocytes were exposed to cytoskeleton-targeting compounds or matured in control conditions, and their morphology was examined using fluorescent and electron microscopy.
The ultrastructural morphology of dysmorphic oocytes was analyzed. Drug-treated oocytes had their maturation efficiency, chromosome-microtubule configurations, and fine intracellular morphology examined.
TEM revealed ultrastructural characteristics of common oocyte aberrations and indicated that excessive organelle clustering was the underlying cause of 2 of the studied morphotypes. Inhibition experiments showed that disruption of actin, not microtubules, allows for inordinate aggregation of subcellular structures, resembling the ultrastructural pattern seen in morphologically abnormal oocytes retrieved in IVF cycles. These results imply that actin serves as a regulator of organelle distribution during human oocyte maturation.
The ultrastructural analogy between dysmorphic oocytes and oocytes, in which actin network integrity was perturbed, suggests that dysfunction of the actin cytoskeleton might be implicated in generating common cytoplasmic aberrations. Knowledge of human oocytes\' inner workings and the origin of morphological abnormalities is a step forward to a more objective oocyte quality assessment in IVF practice.

Say-Barber-Biesecker-Young-Simpson (SBBYSS) variant of Ohdo syndrome is a rare, autosomal dominant and clinically heterogenous disorder, caused by pathogenic variants in the KAT6B gene located on chromosome 10q22.2. KAT6B encodes a highly conserved histone acetyltransferase belonging to the MYST family. Currently, diseases caused by pathogenic variants in KAT6B (KAT6B-related disorders) comprise two allelic entities: SBBYSS variant of Ohdo syndrome and genitopatellar syndrome (GPS). Increase in the number of cases with overlapping GPS/SBBYSS phenotype which makes it necessary to redefine this group of phenotypes as KAT6B-related disorders or KAT6B spectrum disorders. Individuals with SBBYSS usually present with facial abnormalities, hypotonia, joint laxity, feeding problems, and long thumbs/great toes. This syndrome also typically involves skeletal problems including patellar hypoplasia/agenesis.
Here we report six SBBYS syndrome patients with the same dysmorphic features but a different course of the disease. One known and five novel KATB6 pathogenic variants were identified by molecular diagnostics using Next Generation Sequencing (NGS).
We present a detailed phenotypic analysis of six individuals with KAT6B-related disorders, in whom a heterozygous pathogenic variant in KAT6B gene was found. In all of our patients facial dysmorphism as well as developmental and speech delay were present. Additionally, all but one patients presented with hypotonia, ocular abnormalities and long thumbs. Most of our probands showed blepharophimosis and skeletal (mainly knee) defects. Contrary to previously reported severe patellar defects (hypoplasia/agenesis) anomalies presented by our patients were less severe (dysplasia, habitual dislocation, subluxation) referring to KAT6B-related disorders.
While most of the anomalies found in our patients comply with SBBYSS criteria, phenotypic differences in our probands support a broader spectrum of the disease phenotype. To establish the range of this spectrum, a detailed analysis of clinical variability among patients with SBBYSS requires further investigation.