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Indian Journal of Dermatology,... 2020
Topics: Acrocephalosyndactylia; Female; Humans; Hyperpigmentation; Middle Aged
PubMed: 32769309
DOI: 10.4103/ijdvl.IJDVL_648_19 -
Journal of Medical Systems Jul 2020This paper presents a methodological procedure, based on the anatomical reconstruction and constrained deformation, to design custom-made implants for forehead...
This paper presents a methodological procedure, based on the anatomical reconstruction and constrained deformation, to design custom-made implants for forehead augmentation in people affected by Apert syndrome, experiencing a frontal bone deficiency. According to the anthropometric theory, a cranial landmarks identification procedure was applied to retrieve, from a repository, a healthy skull, used as reference geometry for implant modelling. Then, using constrained deformation and free-form modelling techniques, it was possible to design a patient-specific implant. At last, the implant was realised using a custom mould, specially designed according to the patient's needs to provide an accurate fit of the defect site. The design procedure was tested on a patient suffering from Apert syndrome. Three implants were virtually modelled and 3D-printed for pre-surgical evaluation. Their shapes were 3D compared with a reference one (handcrafted by a surgeon) to test the accuracy. Deviations are negligible, and the customised implant fulfilled the surgeon's requirements.
Topics: Acrocephalosyndactylia; Computer-Aided Design; Forehead; Humans; Imaging, Three-Dimensional; Plastic Surgery Procedures; Tomography, X-Ray Computed
PubMed: 32720066
DOI: 10.1007/s10916-020-01611-9 -
Journal of Medical Genetics Jun 2021Pathogenic DNA variants in the GLI-Kruppel family member 3 ( gene are known to cause multiple syndromes: for example, Greig syndrome, preaxial polydactyly-type 4 (PPD4)...
INTRODUCTION
Pathogenic DNA variants in the GLI-Kruppel family member 3 ( gene are known to cause multiple syndromes: for example, Greig syndrome, preaxial polydactyly-type 4 (PPD4) and Pallister-Hall syndrome. Out of these, Pallister-Hall is a different entity, but the distinction between Greig syndrome and PPD4 is less evident. Using latent class analysis (LCA), our study aimed to investigate the correlation between reported limb anomalies and the reported variants in these GLI3-mediated polydactyly syndromes. We identified two subclasses of limb anomalies that relate to the underlying variant.
METHODS
Both local and published cases were included for analysis. The presence of individual limb phenotypes was dichotomised and an exploratory LCA was performed. Distribution of phenotypes and genotypes over the classes were explored and subsequently the key predictors of latent class membership were correlated to the different clustered genotypes.
RESULTS
297 cases were identified with 127 different variants in the gene. A two-class model was fitted revealing two subgroups of patients with anterior versus posterior anomalies. Posterior anomalies were observed in cases with truncating variants in the activator domain (postaxial polydactyly; hand, OR: 12.7; foot, OR: 33.9). Multivariate analysis supports these results (Beta: 1.467, p=0.013 and Beta: 2.548, p<0.001, respectively). Corpus callosum agenesis was significantly correlated to these variants (OR: 8.8, p<0.001).
CONCLUSION
There are two distinct phenotypes within the GLI3-mediated polydactyly population: anteriorly and posteriorly orientated. Variants that likely produce haploinsufficiency are associated with anterior phenotypes. Posterior phenotypes are associated with truncating variants in the activator domain. Patients with these truncating variants have a greater risk for corpus callosum anomalies.
Topics: Acrocephalosyndactylia; Genetic Association Studies; Genetic Variation; Humans; Latent Class Analysis; Limb Deformities, Congenital; Nerve Tissue Proteins; Polydactyly; Syndrome; Zinc Finger Protein Gli3
PubMed: 32591344
DOI: 10.1136/jmedgenet-2020-106948 -
BMJ Case Reports Dec 2019Apert syndrome is a rare genetic disorder that manifests as craniosynostosis, craniofacial and limb dysmorphic features. Mutations in fibroblast growth factor receptor 2...
Apert syndrome is a rare genetic disorder that manifests as craniosynostosis, craniofacial and limb dysmorphic features. Mutations in fibroblast growth factor receptor 2 (FGFR2) gene account for almost all cases. Given the impact it can have throughout life, prenatal management becomes a challenge. A healthy 33-year-old woman, gravida 4, para 0, was referred to routine ultrasound at 22 weeks of gestation. Atypical cranial morphology with prominent forehead, ocular proptosis, hypertelorism and mitten hands were detected. Genetic investigation revealed an FGFR2 gene mutation (c.755C>G(p.Ser252Trp)), confirming the diagnosis. Magnetic resonance showed brachycephaly, turricephaly and cortical malformation. Following counselling, parents requested medical termination of pregnancy. Macroscopic features were consistent with ultrasound findings. This case emphasises the importance of early diagnosis to provide the best family counselling and prenatal management. A multidisciplinary team, consisting of an obstetrician with ultrasonography experience, a medical geneticist and a fetal pathologist, should conduct these cases.
Topics: Abortion, Therapeutic; Acrocephalosyndactylia; Adult; DNA Mutational Analysis; Female; Genetic Counseling; Humans; Infant, Newborn; Karyotyping; Mutation, Missense; Pregnancy; Pregnancy Trimester, Second; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 31822532
DOI: 10.1136/bcr-2019-231982 -
Pediatric Radiology Sep 2019We describe association of olfactory bulb and olfactory tract abnormalities in a child with acrocallosal syndrome caused by kinesin family membrane 7 (KIF7) mutation in...
We describe association of olfactory bulb and olfactory tract abnormalities in a child with acrocallosal syndrome caused by kinesin family membrane 7 (KIF7) mutation in sonic hedgehog pathway. The child also had fontanellar bone in the anterior fontanelle, short sagittal suture, sagittal synostosis, hippocampal malrotation and Joubert malformation. Fontanellar bone has been described in GLI3 mutation and mutant mice models but has not been reported in KIF7 mutation. We briefly review the role of sonic hedgehog pathway and its components KIF7 and GLI3 in forebrain and olfactory system development and also describe olfactory system abnormality in a child with GLI3 mutation.
Topics: Abnormalities, Multiple; Acrocallosal Syndrome; Acrocephalosyndactylia; Brain; Child, Preschool; Female; Humans; Infant; Magnetic Resonance Imaging; Olfactory Bulb; Tomography, X-Ray Computed
PubMed: 31399769
DOI: 10.1007/s00247-019-04480-8 -
Journal of Medical Case Reports Aug 2019Apert syndrome, Online Mendelian Inheritance in Man number 101200, is a rare genetic condition, with autosomal dominant inheritance, characterized by craniosynostosis,...
BACKGROUND
Apert syndrome, Online Mendelian Inheritance in Man number 101200, is a rare genetic condition, with autosomal dominant inheritance, characterized by craniosynostosis, midfacial malformation, and severe symmetrical syndactyly. Apert syndrome is associated with other systemic malformations, including intellectual disability. At least seven mutations in fibroblast growth factor receptor 2 (FGFR2) gene have been found to cause Apert syndrome. Most cases of Apert syndrome are caused by one of the two most frequent mutations located in exon 7 (Ser252Trp or Pro253Arg).
CASE PRESENTATION
A 27-year-old Javanese man presented borderline intellectual functioning and striking dysmorphisms. A clinical diagnosis of Apert syndrome was previously made based on these clinical features. Furthermore, POSSUM software was used before molecular analysis and the result showed suspected Apert syndrome with a cut-off point of 14. Molecular genetic analysis of FGFR2, targeting exon 7, was performed by direct sequencing. In this patient, a missense mutation c.755C>G was detected, changing a serine into a tryptophan (p.Ser252Trp).
CONCLUSION
We report the case of an Indonesian man with Apert syndrome with a c.755C>G (p.Ser252Trp) mutation in the FGFR2 gene. Our patient showed similar dysmorphism to previously reported cases, although cleft palate as a typical feature for p.Ser252Trp mutation was not present. In spite of the accessibility of molecular genetic testing in a few parts of the world, the acknowledgement of clinically well-defined syndromes will remain exceptionally imperative in developing countries with a lack of diagnostic facilities.
Topics: Abnormalities, Multiple; Acrocephalosyndactylia; Adult; High-Throughput Nucleotide Sequencing; Humans; Indonesia; Male; Mutation, Missense; Receptor, Fibroblast Growth Factor, Type 2; Sequence Analysis, DNA
PubMed: 31387623
DOI: 10.1186/s13256-019-2173-x -
Molecular Genetics & Genomic Medicine Sep 2019Preaxial polydactyly type IV, also referred as polysyndactyly, has been described in a few syndromes. We present three generations of a family with preaxial polydactyly...
BACKGROUND
Preaxial polydactyly type IV, also referred as polysyndactyly, has been described in a few syndromes. We present three generations of a family with preaxial polydactyly type IV and other clinical features of Greig cephalopolysyndactyly syndrome (GCPS).
METHODS AND RESULTS
Sequencing analysis of the GLI3 coding region identified a novel donor splice site variant NC_000007.14(NM_000168.6):c.473+3A>T in the proband and the same pathogenic variant was subsequently identified in other affected family members. Functional analysis based on Sanger sequencing of the proband's complementary DNA (cDNA) sample revealed that the splice site variant c.473+3A>T disrupts the original donor splice site, thus leading to exon 4 skipping. Based on further in silico analysis, this pathogenic splice site variant consequently results in a truncated protein NP_000159.3:p.(His123Argfs*57), which lacks almost all functionally important domains. Therefore, functional cDNA analysis confirmed that the haploinsufficiency of the GLI3 is the cause of GCPS in the affected family members.
CONCLUSION
Despite the evidence provided, pathogenic variants in the GLI3 do not always definitely correlate with syndromic or nonsyndromic clinical phenotypes associated with this gene. For this reason, further transcriptomic and proteomic evaluation could be suggested.
Topics: Acrocephalosyndactylia; Child; DNA, Complementary; Female; Genetic Predisposition to Disease; Humans; Middle Aged; Mutation; Nerve Tissue Proteins; Pedigree; Phenotype; Proteomics; Sequence Analysis, DNA; Transcriptome; Zinc Finger Protein Gli3
PubMed: 31325247
DOI: 10.1002/mgg3.878