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BMC Pediatrics May 2024Noonan syndrome (NS) is a rare genetic disease, and patients who suffer from it exhibit a facial morphology that is characterized by a high forehead, hypertelorism,...
BACKGROUND
Noonan syndrome (NS) is a rare genetic disease, and patients who suffer from it exhibit a facial morphology that is characterized by a high forehead, hypertelorism, ptosis, inner epicanthal folds, down-slanting palpebral fissures, a highly arched palate, a round nasal tip, and posteriorly rotated ears. Facial analysis technology has recently been applied to identify many genetic syndromes (GSs). However, few studies have investigated the identification of NS based on the facial features of the subjects.
OBJECTIVES
This study develops advanced models to enhance the accuracy of diagnosis of NS.
METHODS
A total of 1,892 people were enrolled in this study, including 233 patients with NS, 863 patients with other GSs, and 796 healthy children. We took one to 10 frontal photos of each subject to build a dataset, and then applied the multi-task convolutional neural network (MTCNN) for data pre-processing to generate standardized outputs with five crucial facial landmarks. The ImageNet dataset was used to pre-train the network so that it could capture generalizable features and minimize data wastage. We subsequently constructed seven models for facial identification based on the VGG16, VGG19, VGG16-BN, VGG19-BN, ResNet50, MobileNet-V2, and squeeze-and-excitation network (SENet) architectures. The identification performance of seven models was evaluated and compared with that of six physicians.
RESULTS
All models exhibited a high accuracy, precision, and specificity in recognizing NS patients. The VGG19-BN model delivered the best overall performance, with an accuracy of 93.76%, precision of 91.40%, specificity of 98.73%, and F1 score of 78.34%. The VGG16-BN model achieved the highest AUC value of 0.9787, while all models based on VGG architectures were superior to the others on the whole. The highest scores of six physicians in terms of accuracy, precision, specificity, and the F1 score were 74.00%, 75.00%, 88.33%, and 61.76%, respectively. The performance of each model of facial recognition was superior to that of the best physician on all metrics.
CONCLUSION
Models of computer-assisted facial recognition can improve the rate of diagnosis of NS. The models based on VGG19-BN and VGG16-BN can play an important role in diagnosing NS in clinical practice.
Topics: Humans; Noonan Syndrome; Child; Female; Male; Child, Preschool; Neural Networks, Computer; Infant; Adolescent; Automated Facial Recognition; Diagnosis, Computer-Assisted; Sensitivity and Specificity; Case-Control Studies
PubMed: 38783283
DOI: 10.1186/s12887-024-04827-7 -
Surgical Neurology International 2024Orbital hypertelorism is a rare congenital condition caused by craniofacial malformations. It consists of complete orbital lateralization, characterized by an increase...
BACKGROUND
Orbital hypertelorism is a rare congenital condition caused by craniofacial malformations. It consists of complete orbital lateralization, characterized by an increase in distance (above the 95 percentile) of the inner canthal (ICD), outer canthal, and interpupillary distances. It can be approached surgically, and the main techniques are box osteotomy and facial bipartition. The surgical procedure is usually performed before the age of 8. We describe here two patients who underwent late surgical correction using the box osteotomy technique.
CASE DESCRIPTION
Patient 1: A 13-year-old female presenting isolated hypertelorism with 5 cm ICD and left eye amblyopia. Patient 2: A 15-year-old female with orbital hypertelorism, 4.6 cm ICD, and nasal deformity. Both patients underwent orbital translocation surgery and had no neurological disorders.
CONCLUSION
The article reports two cases of isolated hypertelorism treated late with the box osteotomy technique. Both surgeries were successful, with no postoperative complications. It appears that it is possible to obtain good surgical results even in patients who have not been able to undergo surgery previously.
PubMed: 38741988
DOI: 10.25259/SNI_1029_2023 -
BMC Ophthalmology Apr 2024Among sex chromosome aneuploidies, 48, XXYY syndrome is a rare variant. This condition is marked by the existence of an additional X and Y chromosome in males, leading...
BACKGROUND
Among sex chromosome aneuploidies, 48, XXYY syndrome is a rare variant. This condition is marked by the existence of an additional X and Y chromosome in males, leading to a diverse range of physical, neurocognitive, behavioral, and psychological manifestations. Typical characteristics include a tall stature and infertility. Other phenotypes include congenital heart defects, skeletal anomalies, tremors, obesity, as well as the potential for type 2 diabetes and/or peripheral vascular disease.
CASE PRESENTATION
A 6-year-old boy, who had been experiencing progressive vision deterioration in both eyes for the past two years, presented with a history of poor vision, delayed motor skills. The patient was diagnosed with micropenis in the pediatric outpatient clinic. Sparse hair, an unusually tall stature and craniofacial dysmorphology characterized by ocular hypertelorism, depressed nasal bridge, and epicanthic folds were observed. Comprehensive ophthalmic examination revealed high myopia and grade 3 macular hypoplasia. Diagnostic investigations including karyotype analysis and whole-exome sequencing identified an anomalous male karyotype comprising two X and two Y chromosomes, confirming a diagnosis of 48, XXYY syndrome.
CONCLUSIONS
This study underscores the rare association of high myopia and grade 3 macular dysplasia with 48, XXYY syndrome. To our knowledge, this case marks the first recorded instance of macular dysplasia in a patient with 48, XXYY syndrome. This novel finding enhances our understanding of this syndrome's phenotypic variability.
Topics: Humans; Male; Child; Macula Lutea; Myopia, Degenerative; Klinefelter Syndrome; Myopia
PubMed: 38654225
DOI: 10.1186/s12886-024-03456-z -
International Journal of Oral and... Apr 2024To determine the skeletal changes after midface surgery in patients with syndromic craniosynostosis who underwent Le Fort III (LFIII), monobloc (MB), or facial...
To determine the skeletal changes after midface surgery in patients with syndromic craniosynostosis who underwent Le Fort III (LFIII), monobloc (MB), or facial bipartition (FB). This was a retrospective study including 75 patients: 33 treated by LFIII, 29 by MB, and 13 by FB. Twenty-five had a diagnosis of Apert, 39 Crouzon, and 11 craniofrontonasal syndrome. A three-dimensional mesh was created from the preoperative scan and registered to the postoperative scan to visualise the advancement. LFIII at age 7-12 years effectuated a higher mean advancement in the maxillary (15.5 mm) and zygomatic (7.6 mm) regions when compared to ≥13 years (10.2 mm and 5.5 mm). After MB, mean advancement of the fronto-orbital region was higher at <7 years (16.4 mm), and similarly lower at ages 7-12 (13.8 mm) and ≥13 (12.5 mm). The mean preoperative inter-dacryon distance (34.4 ± 4.4 mm) was reduced by 8.7 ± 4.2 mm after FB without distraction (n = 10). More advancement was seen when midface surgery was performed at a younger age, due to more severe cases and a desire for overcorrection. The highest mean advancement was observed in the fronto-orbital region. Antero-inferior rotational movement was seen after all three techniques.
PubMed: 38594167
DOI: 10.1016/j.ijom.2024.03.010 -
Proceedings of the National Academy of... Apr 2024Despite the conservation of genetic machinery involved in eye development, there is a strong diversity in the placement of eyes on the head of animals. Morphogen...
Despite the conservation of genetic machinery involved in eye development, there is a strong diversity in the placement of eyes on the head of animals. Morphogen gradients of signaling molecules are vital to patterning cues. During eye development, Wingless (Wg), a ligand of Wnt/Wg signaling, is expressed anterolaterally to form a morphogen gradient to determine the eye- versus head-specific cell fate. The underlying mechanisms that regulate this process are yet to be fully understood. We characterized ( ortholog of human SATB1), a K50 homeodomain transcription factor, as a dorsal eye gene, which regulates Wg signaling to determine eye versus head fate. Across species, Dve is expressed in the dorsal head vertex region where it regulates transcription. Second, Dve suppresses eye fate by down-regulating retinal determination genes. Third, the -expressing dorsal head vertex region is important for Wg-mediated inhibition of retinal cell fate, as eliminating the Dve-expressing cells or preventing Wg transport from these -expressing cells leads to a dramatic expansion of the eye field. Together, these findings suggest that Dve regulates Wg expression in the dorsal head vertex, which is critical for determining eye versus head fate. Gain-of-function of SATB1 exhibits an eye fate suppression phenotype similar to Dve. Our data demonstrate a conserved role for Dve/SATB1 in the positioning of eyes on the head and the interocular distance by regulating Wg. This study provides evidence that dysregulation of the Wg morphogen gradient results in developmental defects such as hypertelorism in humans where disproportionate interocular distance and facial anomalies are reported.
Topics: Animals; Humans; Drosophila Proteins; Matrix Attachment Region Binding Proteins; Wnt1 Protein; Drosophila; Retina; Transcription Factors; Gene Expression Regulation, Developmental; Drosophila melanogaster; Body Patterning
PubMed: 38588419
DOI: 10.1073/pnas.2316244121 -
Case Reports in Genetics 2024Hyperphosphatasia with mental disorder (HPMRS) is a rare autosomal recessive disease caused by gene mutations in enzymes involved in the synthesis and remodeling of...
Hyperphosphatasia with mental disorder (HPMRS) is a rare autosomal recessive disease caused by gene mutations in enzymes involved in the synthesis and remodeling of lipids. Seven-month-old boy diagnosed with bilateral glaucoma had a cleft palate, facial dysmorphism, hypertelorism, a broad nasal bridge, and large fleshy earlobes. A brain MRI scan also revealed brain abnormalities. The observed phenotype in a seven-month-old boy is in agreement with the phenotypic features of HPRMS type-4. Whole exome sequencing revealed a possible pathogenic variant of in a homozygous state (c.320C > T, p.Ser107Leu) which supported the diagnosis of HPRMS type-4. We report an unusual presentation for HPMRS and suggest adding this syndrome to the list of differential diagnoses of syndromic congenital glaucoma.
PubMed: 38558875
DOI: 10.1155/2024/3561555 -
Biochimica Et Biophysica Acta.... Apr 2024
Topics: Humans; Cleft Palate; Esophagus; Genetic Diseases, X-Linked; Hypertelorism; Hypospadias; Mutation, Missense; Ubiquitin-Protein Ligases
PubMed: 38508475
DOI: 10.1016/j.bbadis.2024.167126 -
The Pan African Medical Journal 2023Cri-du-chat syndrome is a rare genetic disorder, due to a deletion of the short arm of chromosome 5 (5p-). Its incidence is ranging from 1/15000 to 1/50000 live births....
Cri-du-chat syndrome is a rare genetic disorder, due to a deletion of the short arm of chromosome 5 (5p-). Its incidence is ranging from 1/15000 to 1/50000 live births. This was a one-day-old male newborn from a non-consanguineous marriage, the first pregnancy uncomplicated and carried to term with a birth weight of 2295g. Clinical examination revealed: craniofacial dysmorphism with hypertelorism and microcephaly, hypotonia, poor suction and clubfoot more marked on the right, the rest of the examination was unremarkable. During hospitalization, a high-pitched monochromatic cry mimicking a cat's meow was observed. The clinical diagnosis was confirmed by fluorescence in situ hybridization, showing a deletion of the short arm of chromosome 5 (5p15.2). The basic malformative work-up came back without any other abnormalities. The association of a high-pitched monochromatic cry with craniofacial dysmorphism in a newborn should indicate the need for cytogenetic study, in particular fluorescence in siti hybridization.
Topics: Infant, Newborn; Female; Pregnancy; Male; Humans; Cri-du-Chat Syndrome; In Situ Hybridization, Fluorescence; Suction; Musculoskeletal Abnormalities; Muscle Hypotonia
PubMed: 38435407
DOI: 10.11604/pamj.2023.46.109.42239 -
Molecular Genetics & Genomic Medicine Feb 2024TNRC6B deficiency syndrome, also known as global developmental delay with speech and behavioral abnormalities (MIM 619243), is a rare autosomal dominant genetic disease...
Novel variants in TNRC6B cause global developmental delay with speech and behavioral abnormalities, short stature, low body weight, café-au-lait spots, and metabolic abnormality.
BACKGROUND
TNRC6B deficiency syndrome, also known as global developmental delay with speech and behavioral abnormalities (MIM 619243), is a rare autosomal dominant genetic disease mainly characterized by facial dysmorphism, developmental delay/intellectual disability (DD/ID), speech and language delay, fine and motor delay, attention deficit and hyperactivity disorder (ADHD), and variable behavioral abnormalities. It is caused by heterozygous variant in the TNRC6B gene (NM_001162501.2, MIM 610740), which encodes the trinucleotide repeat-containing adaptor 6B protein.
METHODS
In this study, two Chinese patients with TNRC6B deficiency syndrome were recruited, and genomic DNA extraction from peripheral blood leukocytes of these parents and their family members was extracted for whole-exome sequencing and Sanger sequencing.
RESULTS
Here, we report two unrelated Chinese patients diagnosed with TNRC6B deficiency syndrome caused by novel de novo likely pathogenic or pathogenic TNRC6B variants c.335C>T (p.Pro112Leu) and c.1632delC (p.Leu546fs*63), which expands the genetic spectrum of TNRC6B deficiency syndrome. The clinical features of the patients were DD/ID, delayed speech, ADHD, behavioral abnormalities, short stature, low body weight, café-au-lait spots, metabolic abnormalities, and facial dysmorphism including coarse facial features, sparse hair, frontal bossing, hypertelorism, amblyopia, strabismus, and downslanted palpebral fissures, which expands the phenotype spectrum associated with TNRC6B deficiency syndrome.
CONCLUSION
This study expands the genotypic and phenotypic spectrum of TNRC6B deficiency syndrome. Our findings indicate that patients with TNRC6B deficiency syndrome should be monitored for growth and metabolic problems and therapeutic strategies should be developed to address these problems. Our report also suggests the clinical diversity of TNRC6B deficiency syndrome.
Topics: Humans; Body Weight; Cafe-au-Lait Spots; Intellectual Disability; Musculoskeletal Abnormalities; RNA-Binding Proteins; Speech
PubMed: 38404251
DOI: 10.1002/mgg3.2408 -
Cureus Jan 2024Pathogenic variants in mitochondrial calcium uptake 1 ( manifest phenotypically heterogeneously but most frequently in the brain and skeletal muscle. Dolichocephaly,...
Pathogenic variants in mitochondrial calcium uptake 1 ( manifest phenotypically heterogeneously but most frequently in the brain and skeletal muscle. Dolichocephaly, arachnodactyly, diplopia, and distal myopathy have not been reported in carriers of a pathogenic variant. The patient is a 23-year-old female with consanguineous parents (first cousins) who was a carrier of the homozygous variant c.553C>T, phenotypically presenting with developmental delay, intellectual disability, ataxia, dysmorphia (dolichocephaly, arachnodactyly, clinodactyly, hypertelorism, wide nasal bridge), myopathy (ptosis, double vision, strabismus, distal limb weakness, diffuse wasting, hypotonia), hyperextensible joints and hyperkyphosis. Features not previously described were dolichocephaly, arachnodactyly, broad nasal bridge, double vision, and distal myopathy. She was treated with physical therapy, speech therapy, and occupational therapy and received escitalopram and mirtazapine for concomitant depression, anxiety disorder, and insomnia. The presented case shows that the phenotypic heterogeneity of pathogenic variants is even greater than previously assumed. Treatment of -related phenotypes is symptomatic, but these patients benefit from physical therapy, behavioral therapy, speech therapy, and antidepressant treatment.
PubMed: 38380193
DOI: 10.7759/cureus.52672