Typical Facial Appearance Research Articles

Clinical and molecular features of first two-sibling-Cambodian girls with musculocontractural Ehlers-Danlos syndrome

Musculocontractural Ehlers-Danlos syndrome (mcEDS) is a rare autosomal recessive connective tissue disorder. To our knowledge, mcEDS has not previously been reported in Cambodia. Here, we report clinical presentations and a novel variant of CHST14 causing mcEDS in the two siblings in Cambodia. These patients from a non-consanguineous parents presented with clubfeet at birth, contractures of thumbs and feet, a typical facial appearance, and normal cognitive development. The elder sister had severe phenotypic features than the younger sister. They have been prone to ecchymosis and hematomas with minor accidents since young age, without accurate diagnosis, or confused with von-willebrand disease. Genetic consultation and confirmed by a genetic analysis revealed a novel variant, c.994-997dup, (Pro333Glnfs×23) of CHST14. Treated with oral desmopressin and daily vitamin C supplementation over 1-year-period of follow-up, the bleeding has been improved. The purpose of this article is to describe the clinical and molecular features and to show the missed or inaccurate diagnosis of this rare syndrome, which, consequently, results in suboptimal symptomatic management.

Psychological status of patients with skeletal Class III malocclusion undergoing bimaxillary surgery: A comparative study.

Skeletal Class III malocclusion can significantly impact psychological well-being. Although bimaxillary surgery is a well-established corrective intervention, its psychological effects are not fully understood. This study aims to investigate changes in self-esteem, sensitivity to criticism, and social appearance anxiety following surgery to inform targeted nursing interventions for psychological adaptation. This comparative study included 205 participants: 150 patients with skeletal Class III malocclusion who underwent bimaxillary surgery, and a control group of 55 individuals without malocclusion. The malocclusion group had a mean age of 21.99 ± 2.28 years (96 males, 109 females). The control group consisted of department interns with Class I occlusion, normal overjet and overbite, and typical facial appearance, with a mean age of 21.61 ± 2.40 years (26 males, 29 females). Psychological assessments, validated for reliability, measured self-esteem, sensitivity to criticism, and social appearance anxiety before and after surgery. Statistical analyses, including independent sample t tests and one-way ANOVA, were performed to compare outcomes between the groups, with a significance level set at P < .05. Preoperative assessments revealed that patients with skeletal Class III malocclusion had significantly lower self-esteem and higher sensitivity to criticism and social appearance anxiety compared to the control group (P < .05). Postoperatively, there were modest improvements in self-esteem and significant reductions in sensitivity to criticism and social appearance anxiety, though levels of social appearance anxiety remained higher than those in the control group (P < .05). No significant differences in self-esteem and sensitivity to criticism were observed between the surgical and control groups postoperatively (P > .05). Within-group comparisons showed significant improvements in all measures after surgery (P < .05). Bimaxillary surgery positively affects the psychological well-being of patients with skeletal Class III malocclusion, enhancing self-esteem and reducing sensitivity to criticism and social appearance anxiety. However, some psychological concerns persist, indicating a need for targeted nursing interventions to further support these patients' psychological well-being.

A Kabuki syndrome presenting with strabismus: case report

Kabuki syndrome affects many systems and is characterized by a typical facial appearance and is a genetically inherited disease. Ophthalmological involvement is quite common and can be diagnostic. In this article, we aimed to present the ophthalmological findings of our patient with Kabuki syndrome, who was diagnosed and treated based on ophthalmological findings.

Beyond the known phenotype of sotos syndrome: a 31-individuals cohort study.

Sotos Syndrome (SS, OMIM#117550) is a heterogeneous genetic condition, recognized by three main clinical features present in most cases: overgrowth with macrocephaly, typical facial appearance and different degrees of intellectual disability. Three different types are described caused by variants or deletions/duplications in NSD1, NFIX and APC2 genes. We aimed to describe a cohort of pediatric patients reporting the typical and unexpected findings in order to expand the phenotype of this syndrome and trying to find genotype-phenotype correlations. In our referral center, we collected and analyzed clinical and genetic data of 31-patients cohort diagnosed with SS. All of them presented with overgrowth, typical dysmorphic features and different degree of developmental delay. Although structural cardiac defects have been reported in SS, non-structural diseases such as pericarditis were outstanding in our cohort. Moreover, we described here novel oncological malignancies not previously linked to SS such as splenic hamartoma, retinal melanocytoma and acute lymphocytic leukemia. Finally, five patients suffered from recurrent onychocryptosis that required surgical procedures, as an unreported prevalent medical condition. This is the first study focusing on multiple atypical symptoms in SS at the time that revisits the spectrum of clinical and molecular basis of this heterogeneous entity trying to unravel a genotype-phenotype correlation.

Configural properties of face portraits change between childhood and adulthood

Adult observers are sensitive to the configuration of facial features within a face, able to distinguish between relative differences in feature spacing, and detecting deviations from typical facial appearance. How does the representation of the typical configuration of facial features develop? While there is a great deal of work describing children’s developing abilities to detect differences in feature spacing across face images, there is substantially less work examining what children think constitutes a typical arrangement of facial features. In the current study, we investigated this issue using a production task in which adults and 5- to 10-year-old children created a face “portrait” by arranging the eyes, nose, and mouth of a standard face within an empty outline. Using this simple task, we found differences in face configuration across age groups, such that children of all ages made far larger errors than adult participants, expanding facial features outward from the center of the face more than adults. These results were not affected by face inversion, potentially implying a domain-general rather than face-specific process. We also found that children of all ages endorsed the correct configuration as a best likeness in a perceptual task. We discuss these results in terms of ongoing debate regarding the extent to which configural processing is a meaningful component of face recognition and the conclusions we can draw from production paradigms as compared to purely perceptual tasks.

Cerebral gigantism: sotos syndrome: A case report

Sotos syndrome is a genetic condition characterized by overgrowth, advanced bone age and a typical facial appearance. Oral findings include a high-arched palate, premature eruption of the teeth and dental agenesis. This paper documents a child diagnosed with Sotos Syndrome and describes the primary clinical features, the disease-specific, oral and dental findings, and dental care management of this patient.

Alternative splicing of BUD13 determines the severity of a developmental disorder with lipodystrophy and progeroid features

In this study we aimed to identify the molecular genetic cause of a progressive multisystem disease with prominent lipodystrophy. In total, 5 affected individuals were investigated using exome sequencing. Dermal fibroblasts were characterized using RNA sequencing, proteomics, immunoblotting, immunostaining, and electron microscopy. Subcellular localization and rescue studies were performed. We identified a lipodystrophy phenotype with a typical facial appearance, corneal clouding, achalasia, progressive hearing loss, and variable severity. Although 3 individuals showed stunted growth, intellectual disability, and died within the first decade of life (A1, A2, and A3), 2 are adults with normal intellectual development (A4 and A5). All individuals harbored an identical homozygous nonsense variant affecting the retention and splicing complex component BUD13. The nucleotide substitution caused alternative splicing of BUD13 leading to a stable truncated protein whose expression positively correlated with disease expression and life expectancy. In dermal fibroblasts, we found elevated intron retention, a global reduction of spliceosomal proteins, and nuclei with multiple invaginations, which were more pronounced in A1, A2, and A3. Overexpression of both BUD13 isoforms normalized the nuclear morphology. Our results define a hitherto unknown syndrome and show that the alternative splice product converts a loss-of-function into a hypomorphic allele, thereby probably determining the severity of the disease and the survival of affected individuals.

A de novo and novel nonsense variants in ASXL2 gene is associated with Shashi–Pena syndrome

This ASXL2 gene encodes a member of a family of epigenetic regulators that bind various histone-modifying enzymes and are involved in the assembly of transcription factors at specific genomic loci. Recent research has found that pathogenic variants in ASXL2 gene can lead to Shashi–Pena syndrome. However, clinical reports of individuals with damaging ASXL2 variants were limited and clinical phenotypic information may also be incomplete at present. Here, we reported a patient from Chinese family presenting with Shashi–Pena syndrome duo to a nonsense variant c.2485C > T; p. (Gln829*) in ASXL2 and analyzed the clinical phenotypes of the patient. In addition to the typical facial appearance, feeding difficulty, cardiac dysfunction and developmental delay, the patient also demonstrated multiple clinical problems not reported in other published cases, including granulocytopenia, thrombocytopenia and “single transverse palmar crease”. Additionally, this is also the first case of premature death associated to Shashi–Pena syndrome induced by ASXL2 variants in a Chinese population. Our results provided important information for genetic counseling of the family and broaden the spectrum of phenotypes and genetic variations of the syndrome.

Use of growth hormone in region 19p13.3 microduplication syndrome in girl with central early puberty: a clinical case report

Chromosomal mutations involving 19p13.3 have been described as pathogenic. clinical and phenotypic features can include, in most cases, psychomotor development delay, microcephaly, typical facial appearance, hand and foot anomalies, umbilical hernia, hypotonia, and low percentage of lean mass. The main types of mutation found on this chromosome are deletion or duplication. Short stature is often the cause of medical demand and the use of exogenous GH for patients with this syndrome is not beneficial. This article reports the case of a 5-year-old girl who sought medical help due to short stature and was diagnosed with this syndrome. Furthermore, this case study may contribute to the dissemination in the medical community about the association of this genetic mutation with the child's clinical condition, warning about this syndrome, and the possibility of the occurrence of early puberty. This study was analyzed and approved by the Research Ethics Committee (CEP) according to a substantiated opinion number 4.765.113.

A Case of Geroderma Osteodysplasticum Syndrome: Unique Clinical Findings

Geroderma osteodysplasticum (GO; MIM 231070) is characterized by a typical progeroid facial appearance, wrinkled, lax skin, joint laxity, skeletal abnormalities with variable degree of osteopenia, frequent fractures, scoliosis, bowed long bones, vertebral collapse, and hyperextensible fingers. The disorder results from mutations in the GORAB - golgin, RAB6 interacting. This gene encodes a member of the golgin family, a group of coiled-coil proteins on golgin. That maps to chromosome 1q24. The encoded protein has a function in the secretory pathway. Was identified by-teIrminal kinase-like protein, and thus it may function in mitosis? Mutations in this gene have been associated with geroderma osteodysplastica. Herein, we describe the clinical presentation of one young male patient from related Saudi parents. mutations, a homozygous Frameshift mutation (c.306dup p.(pro 103 Thrfs*20). Interestingly, phenotypic variability was observed in this patient with GO features that were atypical than the cases reported in the literature. As he looks tall stature where the most of cases reported were short and arachnodactyly of fingers which mimic and other syndromes.

Kabızlık ve Üfürümle Tespit Edilen Williams-Beuren Sendromu

Williams-Beuren Syndrome Detected with Constipation and Murmur Williams-Beuren syndrome (WBS) is a rare disease that occurs as a result of microdeletion of 11.23 of the long arm of chromosome 7, with a frequency of 1/20.000-30.000. Typical facial appearance, mental retardation, various congenital cardiovascular anomalies and endocrinological disorders may accompany this syndrome. In cases suspected as a result of clinical and laboratory findings, the diagnosis is made by showing the deletion of the mentioned region using the fluorescent in situ hybridization (FISH) method. We detected WBS in a 17-month-old male patient who presented with chronic constipation and had peripheral pulmonary stenosis in echocardiography performed with accompanying clinical findings, and aimed to emphasize the importance of multidimensional evaluation and early diagnosis. Keywords: Congenital heart disease, pulmonary stenosis, microdeletion syndromes, constipation, Williams-Beuren syndrome

Natural histories of patients with Wolf-Hirschhorn syndrome derived from variable chromosomal abnormalities.

Wolf-Hirschhorn syndrome (WHS) is a subtelomeric deletion syndrome affecting the short arm of chromosome 4. The main clinical features are a typical craniofacial appearance, growth deficiency, developmental delays, and seizures. Previous genotype-phenotype correlation analyses showed some candidate regions for each clinical finding. The WHS critical region has been narrowed into the region 2 Mb from the telomere, which includes LETM1 and WHSC1; however, this region is insufficient to cause "typical WHS facial appearance". In this study, we identified 10 patients with a deletion involving 4p16.3. Five patients showed pure terminal deletions and three showed unbalanced translocations. The remaining patients showed an interstitial deletion and a suspected inverted-duplication-deletion. Among 10 patients, one patient did not show "typical WHS facial appearance" although his interstitial deletion included LETM1 and WHSC1. On the other hand, another patient exhibited "typical WHS facial appearance" although her small deletion did not include LETM1 and WHSC1. Instead, FGFRL1 was considered as the candidate for this finding. The largest deletion of 34.7 Mb was identified in a patient with the most severe phenotype of WHS.

Prenatal diagnosis of Wolf-Hirschhorn syndrome: from ultrasound findings, diagnostic technology to genetic counseling.

Wolf-Hirschhorn syndrome (WHS) is a contiguous gene syndrome due to terminal chromosome 4p deletions. We explored prenatal diagnosis of WHS by ultrasound as well as karyotype and single nucleotide polymorphism array (SNP array) to characterize the structural variants of WHS prenatally. Ten prenatal cases of WHS were evaluated for the indication of the invasive testing, the ultrasound features, and cytogenetic and microarray results. Eight cases were diagnosed by karyotyping and SNP array, while two cases were detected only by SNP array. Combining our cases with 37 prenatal cases from the literature, the most common sonographic features were IUGR (97.7%) and typical facial appearance (82.9%). Other less common phenotypes included renal hypoplasia (36.2%), cardiac malformation (29.8%), cleft lip and palate (25.5%), cerebral abnormalities (25.5%), skeletal anomalies (21.3%), and increased nuchal translucency/nuchal fold thickness (NT/NF) (19%). The most common intrauterine phenotypes of WHS were severe IUGR and typical facial appearance with other less consistent ultrasound findings. Noninvasive prenatal testing (NIPT) is one very promising screening tool for WHS. SNP array can improve diagnostic precision for detecting WHS, especially for the cryptic aberrations that cannot be identified by the traditional karyotyping. Ectopic kidney may be a previously unrecognized phenotype of WHS.

Novel heterozygous mutation in TBX1 in an infant with hypocalcemic seizures.

.Patients with 22q11.2 deletion syndrome have characteristic facial appearance, palate abnormalities, hypoparathyroidism, thymic hypoplasia, and congenital heart disease. The 22q11.2 region includes TBX1 and 30 other genes. Analysis of Tbx1 transgenic mice showed that TBX1 was associated with the 22q11.2 deletion syndrome. In humans, TBX1 mutations have been reported in 22q11.2 deletion-negative patients with velocardiofacial syndrome or DiGeorge syndrome. Genotype-phenotype correlations are not fully understood in these patients. We report the case of an infant with a novel heterozygous TBX1 mutation who experienced hypocalcemic seizures. This patient had no palate abnormalities, cardiac anomalies, or the typical facial appearance observed in 22q11.2 deletion syndrome. The presence of thymic hypoplasia prompted us to perform G-banding, fluorescent in situ hybridization, and subsequent TBX1 analysis. We emphasize the importance of diagnosing thymic hypoplasia in hypocalcemic infants without 22q11.2 deletion for detecting TBX1 mutations.

Circulating T Cells of Patients with Nijmegen Breakage Syndrome Show Signs of Senescence

PurposeThe Nijmegen breakage syndrome (NBS) is an inherited genetic disorder characterized by a typical facial appearance, microcephaly, growth retardation, immunodeficiency, and a strong predisposition to malignancies, especially of lymphoid origin. NBS patients have a mutation in the NBN gene which involves the repair of DNA double-strand breaks (DSBs). Here we studied the peripheral T cell compartment of NBS patients with a focus on immunological senescence.MethodsThe absolute numbers and frequencies of the different T cell subsets were determined in NBS patients from young age till adulthood and compared to age-matched healthy individuals (HI). In addition, we determined the expression of senescent T cell markers and the signal joint T cell receptor excision circles (sjTRECs) content.ResultsOur results demonstrate that NBS patients have reduced T cell numbers. NBS patients showed lower numbers of αβ+ T cells, but normal γδ+ T cell numbers compared to HI. Concerning the αβ+ T cells, both CD4+ as well as CD8+ T cells were excessively reduced in numbers compared to aged-matched HI. In addition, NBS patients showed higher frequencies of the more differentiated T cells expressing the senescent cell marker CD57 and did not express co-stimulatory molecule CD28. These effects were already present in the youngest age group. Furthermore, NBS patients showed lower sjTREC content in their T cells possibly indicative of a lower thymic output.ConclusionsWe conclude that circulating T cells from NBS patients show signs of a senescent phenotype which is already present from young age on and which might explain their T cell immune deficiency.

Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia.

Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings. Over time, the majority of affected individuals developed prominent cervical, cranial and laryngeal dystonia. Marked clinical benefit, including the restoration of independent ambulation in some cases, was observed following deep brain stimulation (DBS). These findings highlight a clinically recognizable and potentially treatable form of genetic dystonia, demonstrating the crucial role of KMT2B in the physiological control of voluntary movement.

Cephalometrics in Stickler syndrome: Objectification of the typical facial appearance.

Stickler syndrome is a connective tissue disorder characterized by orofacial, ocular, skeletal and auditory symptoms. The orofacial phenotype mainly consists of midfacial hypoplasia, micrognathia and cleft palate. Large phenotypic variability is evident though. Few studies have tried to substantiate the typical facial appearance in Stickler syndrome patients. Molecularly confirmed Stickler patients were invited to undergo cephalometric analysis based on a lateral radiograph in standardized conditions. Angular and linear measurements were performed according to Steiner's and Sassouni's analysis and compared with age- and gender-matched reference values. Thirteen patients aged 10-62y were included, twelve of whom had type 1 Stickler syndrome (COL2A1 mutation) and one type 2 Stickler syndrome (COL11A1 mutation). The position of maxilla and mandible relative to the cranial base was not significantly different from the reference population (S-N-A: p=0.73, S-N-B: p=0.43). The mandibular plane and y-axis showed an elevated angle with the cranial base in most patients, although not significant for the total group (S-N to Go-Me: p=0.20, S-N to S-Gn: p=0.18). Dental analysis was normal, except for a higher overjet value (p=0.006) and a higher angle between occlusal plane and Frankfort plane (p=0.022). Cephalometric analysis was not able to thoroughly prove the abnormal facial appearance in Stickler syndrome. The majority of patients had normal dentofacial proportions. The most frequently observed anomaly in our series is a rather short and posteriorly rotated mandible, but clinical variability is high.

Carbonic anhydrase II deficiency syndrome: A report of 18 new Saudi Arabian cases

To describe the clinical, radiological and biochemical features of 18 new Saudi Arabian children with the carbonic anhydrase II deficiency syndrome, who have been in follow up at Al-Rass General Hospital in the period from September 2004 to September 2008. The medical records of these children were reviewed. The diagnosis was based on the typical clinical, radiological and biochemical evidence of the disease. These patients had characteristic clinical features, which include typical facial appearance and growth and psychomotor retardation. All patients had renal tubular acidosis (the majority have distal renal tubular acidosis) and metaphyseal osteopetrosis. Intracerebral calcifications were reported in 9 out of the 15 children in whom cranial tomography scan of the brain was performed. Half had nystagmus, about half had squint, another half had visual impairment and two patients had optic atrophy and total blindness. Two patients had hepatosplenomegaly with anemia and thrombocytopenia due to bone marrow involvement. Four patients had spastic quadriplegia and three patients had pectus carinatum. The median age of diagnosis was significantly lower than that reported, and two of the patients reported in this study represent the first two cases to be diagnosed at birth. Their intrauterine growth was normal, however radiological evidence of osteopetrosis were reported at birth, but renal acidosis developed at around 2 weeks of age. The syndrome of carbonic anhydrase II deficiency is prevalent in this region of Saudi Arabia. The disease has serious complications and early diagnosis is important. This series included the first two cases that were diagnosed at birth and also showed that central nervous system complications are common presentation of this syndrome.

Alagille sendromu’na eşlik eden kronik böbrek yetmezliği: olgu sunumu

Introduction : Alagille syndrome is an autosomal dominant disorder that affects intrahepatic bile ducts, skeletal, renal, cardiac, and central nervous system and characterized with typical facial appearance. Case : A female newborn with the antenatal diagnosis of right hypoplastic kidney was hospitalized following the birth. One of her siblings with Jagged 1 mutation has died because of renal and liver failure. Our case had total and direct hyperbilirubinemia. Renal ultrasonography revealed bilateral dysplastic kidney. Peripheral pulmonary stenosis was diagnosed with echocardiography. She has posterior embryotoxon on eye examination. Although liver biopsy could not be performed because of fungal peritonitis, Allagille syndrome with the renal failure secondary to bilateral dysplastic kidney was thought with the family history, clinical and laboratory findings. Conclusion : We presented this atypical case coinciding with bilateral congenital dysplastic kidneys and chronic renal failure.

Branchio–oculo–facial syndrome

Branchio-oculo-facial syndrome (BOFS) is a rare autosomal dominant condition with variable expressivity, caused by mutations in the TFAP2A gene. We report a three generational family with four affected individuals. The consultand has typical features of BOFS including infra-auricular skin nodules, coloboma, lacrimal duct atresia, cleft lip, conductive hearing loss and typical facial appearance. She also exhibited a rare feature of preaxial polydactyly. Her brother had a lethal phenotype with multiorgan failure. We also report a novel variant in TFAP2A gene. This family highlights the variable severity of BOFS and, therefore, the importance of informed genetic counselling in families with BOFS.