Case Report: Potocki-Lupski Syndrome in Five Siblings

Potocki-Lupski syndrome (PTLS) is a rare developmental disorder resulting from the partial duplication of the short arm of chromosome 17. Affected children may have hypotonia, facial dysmorphism, or neurological abnormalities. PTLS is also frequently associated with failure to thrive due to swallowing difficulties or growth hormone deficiency. We report the first Romanian family (a mother and her five children) diagnosed with PTLS (17p11.2 microduplication). Fortunately, they present a less severe form of the disease. The neurological manifestations (speech delay, mild intellectual disability) are associated with craniofacial dysmorphism (microcephaly, micrognathia, triangular face, broad forehead, long chin, prominent ears, dolichocephaly, down slanting palpebral fissures). The diagnostic was established using a multiplex ligation-dependent probe amplification technique (MLPA) test, which detected the duplication of three regions of the 17p11.2 chromosome (RAI1, DRC3-6, LLGL1-4RA). Children with PTLS have specific phenotypes (craniofacial dysmorphism or neurological manifestations), which must draw the pediatrician's attention to a possible genetic condition. However, every child with this disease is unique and may have a different clinical presentation. A multi-disciplinary team is needed for the management of these patients. The parent's counseling and genetic advice are essential for a family with children with PTLS.

Identification of SOFT syndrome caused by a pathogenic homozygous splicing variant of POC1A: a case report

Background Pathogenic variants in POC1A led to SOFT syndrome and variant POC1A-related (vPOC1A) syndrome. SOFT syndrome is a rare primordial dwarfism condition characterized by short stature, onychodysplasia, facial dysmorphism and hypotrichosis.The main clinical differences between SOFT and vPOC1A syndrome include dyslipidemia with insulin resistance and acanthosis nigricans. To our knowledge, this is the first report of a SOFT syndrome patient diagnosed with a homozygous splicing variant, which could help to extend our understanding of the genotypic and phenotypic information of the disease. Case presentation We reported a seven-year-old boy with SOFT syndrome. The patient presented symmetrical short stature and facial features, including prominent forehead, inverted triangular face, epicanthal fold, small teeth and enlarged ears. Laboratory tests displayed mild insulin resistance. Whole-exome sequencing (WES) led to the identification of a homozygous splicing variant (c.981+1G>A) in POC1A gene of the patient, which was inherited from his heterozygous parents confirmed by Sanger sequencing. Further transcriptional experiments of the splicing variant revealed aberrant percentage of exon 9 skipping transcripts. Conclusions This is the firstly reported case of a SOFT syndrome patient with a novel homozygous splicing variant and detailed delineation of the aberrant transcript in proband and carrier of the variant in Chinese. Our study enriched mutational spectrum of POC1A which could help in further genetic diagnosis and counselling of SOFT syndrome patients.

Deletion of 16q22.2q23.3 in a Boy with a Phenotype Reminiscent of Silver-Russell Syndrome

A 15-month-old boy presented with growth and global developmental delay, feeding difficulties, sleep disturbance and several minor anomalies, including a large anterior fontanel, relative macrocephaly, and a triangular face. Clinical suspicion prompted genetic investigations for Silver-Russell syndrome and related disorders. SNP array analysis led to the diagnosis of an approximately 10-Mb large deletion of the long arm in chromosome 16q22.2q23.3. Interstitial deletions of 16q show a wide variability of related features; however, considering the differences in size and location of the deletions in the known patients, the phenotypic overlap is surprising. Here, we report a novel microdeletion, compare the proband with data from scientific literature and international databases, and discuss possible diagnostic implications.

EVALUATION OF THE FORECASTED EFFICIENCY OF PERFORMANCE OF RATIONAL ORIENTATION OF THE PRODUCT IN THE WORKSPACE OF ADDITIVE INSTALLATIONS

Preliminary evaluation of the predicted efficiency of the optimization problem of the rational orientation of the product in the working space of layered construction of additive units is proposed to perform based on the analysis of the original triangulation 3D-model of a complex product by its spherical mapping. The condition of reflection on the sphere is that the values of angles in the spherical coordinate system for the faces normal of the triangulated model of product fall into the range of values of a certain triangular face of the sphere model. Examples of evaluation based on the analysis of spherical mapping of the original 3D model of products are considered. Industrial products with different surface complexity were selected as test 3D models. This approach allowed to perform a comparative analysis of the results depending on the design features of the products. The practical implementation was performed in the subsystem of visual assessment of geometric characteristics of triangulated 3D-models, which is part of the technological preparation system for the complex product manufacture by additive methods. This system was developed in NTU "KhPI" Department of Integrated Technologies of Mechanical Engineering named after M.F. Semko.

A de novo frameshift variant of ANKRD11 (c.1366_1367dup) in a Chinese patient with KBG syndrome

Background KBG syndrome is a rare autosomal dominant genetic disease mainly caused by pathogenic variants of ankyrin repeat domain-containing protein 11 (ANKRD11) or deletions involving ANKRD11. Herein, we report a novel de novo heterozygous frameshift ANKRD11 variant via whole exome sequencing in a Chinese girl with KBG syndrome. Case presentation A 2-year-2-month-old girl presented with a short stature and developmental delay. Comprehensive physical examinations, endocrine laboratory tests and imaging examination were performed. Whole‐exome sequencing and Sanger sequencing were used to detect and confirm the variant associated with KBG in this patient, respectively. The pathogenicity of the variant was further predicted by several in silico prediction tools. The patient was diagnosed as KBG syndrome with a short stature and developmental delay, as well as characteristic craniofacial abnormalities, including a triangular face, long philtrum, wide eyebrows, a broad nasal bridge, prominent and protruding ears, macrodontia of the upper central incisors, dental crowding, and binocular refractive error. Her skeletal anomalies included brachydactyly, fifth finger clinodactyly, and left-skewed caudal vertebrae. Electroencephalographic results generally showed normal background activity with sporadic spikes and slow wave complexes, as well as multiple spikes and slow wave complexes in the bilateral parietal, occipital, and posterior temporal regions during non-rapid-eye-movement sleep. Brain MRI showed a distended change in the bilateral ventricles and third ventricle, as well as malformation of the sixth ventricle. Whole exome sequencing revealed a novel heterozygous frameshift variant in the patient, ANKRD11 c.1366_1367dup, which was predicted to be pathogenic through in silico analysis. The patient had received physical therapy since 4 months of age, and improvement of gross motor dysfunction was evident. Conclusions The results of this study expand the spectrum of ANKRD11 variants in KBG patients and provide clinical phenotypic data for KBG syndrome at an early age. Our study also demonstrates that whole exome sequencing is an effective method for the diagnosis of rare genetic disorders.

Novel Variant in PLAG1 in a Familial Case with Silver–Russell Syndrome Suspicion

Silver–Russell syndrome (SRS) is a rare growth-related genetic disorder that is mainly associated with prenatal and postnatal growth retardation. Molecular causes are not clear in all cases, the most common ones being loss of methylation on chromosome 11p15 (≈50%) and maternal uniparental disomy for chromosome 7 (upd(7)mat) (≈10%). However, pathogenic variants in genes such as CDKN1C, HMGA2, IGF2, or PLAG1 have also been described. Previously, two families and one sporadic case have been reported with PLAG1 alterations. Here, we present a case of a female with clinical suspicion of SRS (i.e., intrauterine and postnatal growth retardation, triangular face, psychomotor delay, speech delay, feeding difficulties). No alterations in methylation or copy number were detected at chromosomes 11p15 and 7 using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). The custom panel study by next-generation sequencing (NGS) revealed a frameshift variant in the PLAG1 gene (NM_002655.3:c.551delA; p.(Lys184Serfs *45)). Familial studies confirmed that the variant was inherited from the mother and it was also present in other family members. New evidence of pathogenic alterations in the HMGA2-PLAG1-IGF2 pathway suggest the importance of studying and taking into account these genes as alternative molecular causes of Silver–Russell syndrome.

Novel Findings in Floating-Harbor Syndrome and a Mini-Review of the Literature

Floating-Harbor syndrome (FHS) is a rare autosomal dominant genetic disorder characterized by proportionate short stature with delayed bone maturation, lack of expressive language, and distinctive facial features including a large nose, long eyelashes, deeply set eyes, and triangular face. Mutations in the <i>SRCAP</i> gene cause truncated SNF2-related CREBBP activator protein (SRCAP) and lead to FHS. SRCAP is one of several proteins that act as coactivator for the CREB-binding protein which is associated with Rubinstein-Taybi syndrome (RSTS). This condition likely explains the phenotypic overlap between FHS and RSTS. Herein, we report on a patient with FHS who also had dystrophic toenails, preauricular skin tag, and nasolacrimal duct obstruction which is also defined in patients with RSTS. In summary, the fact that especially nasolacrimal duct obstruction has also been observed in RSTS reinforces the idea that this finding is one of the features of FHS. Assessment of the lacrimal system and examination of skin and nails should be suggested in patients with FHS.

Novel facial characteristics in congenital rubella syndrome: a study of 115 cases in a cardiac hospital of Bangladesh

ObjectiveTo establish novel facial characteristics unique to congenital rubella syndrome (CRS) as prediagnostic criteria to supplement disease diagnosis in patients with or without a history of maternal rubella infection.DesignAn analysis of 115 CRS case series (2018–2020) based on the presence of any of the triad features.SettingOutpatient department of a tertiary care referral cardiac hospital in Dhaka, Bangladesh.ParticipantsIn total, 115 participants (53.1% men) were enrolled. Participants underwent echocardiography if they presented with suspected cardiac symptoms along with deafness, cataract or microcephaly.Main outcome measuresAge, sex and socioeconomic status of the participants; history of maternal vaccination and infection; facial characteristics unique to CRS (triangular face, prominent nose, wide forehead and a whorl on either side of the anterior hairline) named ‘rubella facies’ and frequency of systemic involvements in CRS.ResultsThe median patient age was 2 years. The income of 50.4% of the participating families was <US$1500. Further, 32 mothers (27.8%) were infected with rubella during the first trimester of pregnancy, 15 (13.0%) during the second trimester and 3 (2.6%) during the third trimester. The remainder (65.2%) recalled no history of infection during pregnancy. Rubella facies presented as a triangular-shaped face in 95 (82.6%) cases, a broad forehead in 88 (76.5%) and a prominent nose in 75 (65.2%). A rubella whorl was present on the right or left side of the anterior hairline in 80% and 18.2% of cases, respectively. IgG and IgM antibodies were present in 91.3% and 8.6% of children, respectively. Cataract, deafness, microcephaly, and congenital heart disease were detected in 53.0%, 75.6%, 68.6% and 98.2% of cases, respectively.ConclusionsRubella facies, a set of unique facial characteristics, can support early CRS diagnosis and treatment and may supplement the existing CRS triad.

Bartter Syndrome in Children; A Cause of Severe Hypokalemic Metabolic Alkalosis: Clinical Case Report and Literature Review

Bartter syndrome is an inherited renal tubular disorder caused by a defective salt reabsorption in the thick ascending limb of loop of Henle. It characterized by urinary loss of sodium, potassium, and chloride; hypokalemic metabolic alkalosis; normal blood pressure, high plasma levels of renin and aldosterone. There is phenotypical and genetic variability of Bartter syndrome since were identified five genes responsible for five different forms of Bartter syndrome. The objective of this work is to report a clinical case to study the pathophysiological, clinical, biological and therapeutic features of this syndrome. Materials and Methods: We reported a case of 04-month-old male infant admitted for acute dehydration secondary to polyuro-polydipsia syndrome and vomiting. In clinical presentation the patient had a dysmorphic syndrome with triangular face, protruding ears and flattened nasal root. Laboratory tests revealed hypokalemia, hyponatremia, metabolic alkalosis and hypercalciuria. Treatment with indomethacin was started at 1 mg/kg per day with favorable outcome.

"POLYHEDRAL CONTRACTION" OF TETRAMETHYLAMMONIUM CLOSO-CARBOUNDECABORATE UNDER ACTION OF TRIS(TRIPHENYLPHOSPHINE)RUTHENIUM DICHLORIDE

In this paper the objectives were not only to investigate new promising methods leading to a deep structural rearrangement of carboranes and metallacarboranes but also to try to fix, to isolate and to characterize the intermediates. At the same time considerable attention is paid to the so-called "anti-wade" clusters formed during the reactions, the electronic structure of which does not correspond to their actually observed geometry. It is shown that the interaction of 11-vertex monocarbon closo-carboundecaborane with tris(triphenylphosphine)ruthenium dichloride leads to a series of new metallacarborane complexes. For the first time it was possible to control the process of "polyhedral contraction" of carborane {CB10} → (RuCB10} → {RuCB9} → {RuCB8} → {RuCB6} on the example of ruthenium complex and also to confirm experimentally each stage of the whole process. As a result of the reaction clusters of classical type and electron-deficient isocloso-/hypercloso-rutenacarborans {RuCB8}, {RuCB9} with 2n skeletal electrons were isolated. It is found that the interaction of tetramethylammonium closo-carboundecaborate with tris(triphenylphosphine)ruthenium dichloride proceeds in several stages. The first intermediate 12-vertex cluster is formed by mixing the initial reagents under heterogeneous conditions (methanol-THF, K2CO3, triethylbenzylammonium chloride) at room temperature for 10 hours. When the resulting complex is stirred in a mixture of methanol-THF solvents for 7 days at 20 °C, its almost quantitative transition to 11-vertex rutenacarborane was observed. Further transformation with the formation of a 10-vertex isocloso-rutenacarborane occurs when the methanol solution of this complex is boiled for 15 minutes. When the complex is boiled in methanol for 8 hours we obtained another extraordinary metallacarborane belonging to the rare 8-vertex pileo-clusters with a boron vertex built over the triangular face.