From heterotaxy to VACTER-H syndrome: the clinical variability of ZIC3-related disorders

BACKGROUND: The ZIC3 gene functions as a transcription factor in early stages of left-right body axis formation. Mutations in ZIC3 gene cause a variety of clinical manifestations including isolated congenital heart disease (CHD), heterotaxy & other midline CNS, urogenital & hindgut malformations. We report a four generation family with X-linked heterotaxy associated with a deletion of the ZIC3 gene at ...postprin

Restrictive dermopathy with massive thrombosis: a previously uncreognized finding

Restrictive dermopathy (RD) is a lethal genodermatosis characterized by IUGR, tight and rigid skin, prominent superficial vasculature, epidermal hyperkeratosis, typical facial features, sparse/absent eyelashes and eyebrows, thin dysplastic clavicles, pulmonary hypoplasia and arthrogryposis. It is caused by LMNA or, more frequently, ZMPSTE24 mutations. We report 2 siblings with RD and ZMPSTE24 mutations. CASE REPORT: The mother is 28y G2P1. The couple was 1st cousin of Pakistani origin. Family history was unremarkable. The 1st pregnancy resulted in IUD at 27w, preceded by decreased fetal movement, oligohydramnios and IUGR at 24w. Autopsy was inconclusive and G-banding was not possible. Placenta showed ...postprin

Situs inversus totalis in a fetus with a deletion at 7q36.2 detected on microarray analysis

Laterality disorders are a heterogeneous group of disorders associated with maternal diseases (maternal IDDM), maternal exposures to teratogens (retinoic acid), chromosome abnormalities and single gene disorders (ZIC3 mutation). We report on a fetus with a submicroscopic deletion at 7q36.2 with right atrial isomerism (RAI). CASE: The mother was a 30y G4P1SA2L1 and the father was 35y. Both were healthy and non-consanguineous and their family history was non-contributory. They had a healthy son and daughter and had two miscarriages. MSS was negative. Detailed fetal U/S and echocardiography at 20w showed: RAI with ...postprin

Characteristic Cochlear Hypoplasia in Patients with Walker-Warburg Syndrome: A Radiologic Study of the Inner Ear in alpha-Dystroglycan-Related Muscular Disorders

BACKGROUND AND PURPOSE: Walker-Warburg syndrome, muscle-eye-brain disease, and Fukuyama congenital muscular dystrophy are α-dystroglycan–related muscular disorders associated with brain malformations and eye abnormalities in which no structural inner ear abnormality has been described radiologically. We collected patients from 6 tertiary pediatric hospitals and reported the radiologic features and frequency of inner ear dysplasias. MATERIALS AND METHODS: Patients previously diagnosed clinicoradiologically with Walker-Warburg syndrome, muscle-eye-brain disease, or Fukuyama congenital muscular dystrophy were included. We recorded the pathogenic variant, when available. Brain MR imaging and/or CT findings were reviewed in consensus, and inner ear anomalies were classified according to previous description in the literature. We then correlated the clinicoradiologic phenotype with the inner ear phenotype. RESULTS: Thirteen patients fulfilled the criteria for the Walker-Warburg syndrome phenotype, 8 for muscle-eye-brain disease, and 3 for Fukuyama congenital muscular dystrophy. A dysplastic cochlea was demonstrated in 17/24. The most frequent finding was a pronounced cochlear hypoplasia type 4 with a very small anteriorly offset turn beyond the normal-appearing basal turn (12/13 patients with Walker-Warburg syndrome and 1/11 with muscle-eye-brain disease or Fukuyama congenital muscular dystophy). Two of 8 patients with muscle-eye-brain disease, 1/3 with Fukuyama congenital muscular dystrophy, and 1/13 with Walker-Warburg syndrome showed a less severe cochlear hypoplasia type 4. The remaining patients without Walker-Warburg syndrome were healthy. The vestibule and lateral semicircular canals of all patients were normal. Cranial nerve VIII was present in all patients with diagnostic MR imaging. CONCLUSIONS: Most patients with the severe α‐dystroglycanopathy Walker-Warburg syndrome phenotype have a highly characteristic cochlear hypoplasia type 4. Patients with the milder variants, muscle-eye-brain disease and Fukuyama congenital muscular dystrophy, more frequently have a normal cochlea or milder forms of hypoplasia

The first reported case of the DRAGON gene deletion in human. A case with a de-novo interstitial deletion of chromosome 5q15-21.1

Chondrodysplasia punctata (CDP) is an etiologically heterogenous condition caused by single gene disorders, chromosome abnormalities, maternal diseases or exposures to teratogens. We report a male fetus with rhizomelic CDP associated with deletion at 5q15-5q21.1. This segment contains the DRAGON gene, a bone morphogenetic factor co-receptor, also known as RGMb (repulsive guidance molecule b). It is postulated that its haplo-insufficiency is associated with the phenotype in this fetus. The mother (30yo, G2P0SA1L0) was referred at 19.3 weeks for abnormal antenatal ultrasound findings of short limbs, short splayed digits, brachycephaly, small cistern magna, hypoplastic inferior cerebellar vermis, micrognathia, multiple intracardiac echogenic foci and 2-vessel umbilical cord. There was no history of maternal disease/ exposures. The pregnancy was terminated at 21 weeks. Autopsy confirmed the ultrasound findings and in addition showed brain hypomyelination with ...postprin

What Are You Looking At? Team Fight Prediction Through Player Camera

Esport is a large and still growing industry with vast audiences. Multiplayer Online Battle Arenas (MOBAs), a sub-genre of esports, possess a very complex environment, which often leads to experts missing important coverage while broadcasting live competitions. One common game event that holds significant importance for broadcasting is referred to as a team fight engagement. Professional player's own knowledge and understanding of the game may provide a solution to this problem. This paper suggests a model that predicts and detects ongoing team fights in a live scenario. This approach outlines a novel technique of deriving representations of a complex game environment by relying on player knowledge. This is done by analysing the positions of the in-game characters and their associated cameras, utilising this data to train a neural network. The proposed model is able to both assist in the production of live esport coverage as well as provide a live, expert-derived, analysis of the game without the need of relying on outside sources

Prenatal diagnosis of scalp congenital hemangiopericytoma

Hemangiopericytoma (HPC) is a rare form of vascular tumour. It consists of extensive proliferation of pericapillary cells (pericytes). The most common locations are the head and neck, lower extremities and retroperitoneum. HPC can be benign or malignant. Malignant HPC can metastasize to other areas of the body, usually to the lungs. Up to 5-10% HPCs present in childhood and 5-40% occur in the 1st year of life. We report a fetal case of HPC presenting as an ultrasound finding of a forehead mass. CASE: The proband was a 23y P1 Caucasian woman and her husband was 22y and of same descent. The couple was healthy and non-consanguineous. Early fetal ultrasounds werepostprin

Chitayat syndrome: hyperphalangism, characteristic facies, hallux valgus and bronchomalacia results from a recurrent c.266A>G p.(Tyr89Cys) variant in the ERF gene.

BACKGROUND: In 1993, Chitayat et al., reported a newborn with hyperphalangism, facial anomalies, and bronchomalacia. We identified three additional families with similar findings. Features include bilateral accessory phalanx resulting in shortened index fingers; hallux valgus; distinctive face; respiratory compromise. OBJECTIVES: To identify the genetic aetiology of Chitayat syndrome and identify a unifying cause for this specific form of hyperphalangism. METHODS: Through ongoing collaboration, we had collected patients with strikingly-similar phenotype. Trio-based exome sequencing was first performed in Patient 2 through Deciphering Developmental Disorders study. Proband-only exome sequencing had previously been independently performed in Patient 4. Following identification of a candidate gene variant in Patient 2, the same variant was subsequently confirmed from exome data in Patient 4. Sanger sequencing was used to validate this variant in Patients 1, 3; confirm paternal inheritance in Patient 5. RESULTS: A recurrent, novel variant NM_006494.2:c.266A>G p.(Tyr89Cys) in ERF was identified in five affected individuals: de novo (patient 1, 2 and 3) and inherited from an affected father (patient 4 and 5). p.Tyr89Cys is an aromatic polar neutral to polar neutral amino acid substitution, at a highly conserved position and lies within the functionally important ETS-domain of the protein. The recurrent ERF c.266A>C p.(Tyr89Cys) variant causes Chitayat syndrome. DISCUSSION: ERF variants have previously been associated with complex craniosynostosis. In contrast, none of the patients with the c.266A>G p.(Tyr89Cys) variant have craniosynostosis. CONCLUSIONS: We report the molecular aetiology of Chitayat syndrome and discuss potential mechanisms for this distinctive phenotype associated with the p.Tyr89Cys substitution in ERF

Achondroplasia manifesting as enchondromatosis and ossification of the spinal ligaments: a case report

<p>Abstract</p> <p>Introduction</p> <p>A girl presented with achondroplasia manifested as mild knee pain associated with stiffness of her back. A skeletal survey showed enchondroma-like metaphyseal dysplasia and ossification of the spinal ligaments. Magnetic resonance imaging of the spine further clarified the pathological composites.</p> <p>Case presentation</p> <p>A 7-year-old girl presented with the classical phenotypic features of achondroplasia. Radiographic documentation showed the co-existence of metaphyseal enchondromatosis and development of spinal bony ankylosis. Magnetic resonance imaging showed extensive ossification of the anterior and posterior spinal ligaments. Additional features revealed by magnetic resonance imaging included calcification of the peripheral vertebral bodies associated with anterior end-plate irregularities.</p> <p>Conclusion</p> <p>Enchondromas are metabolically active and may continue to grow and evolve throughout the patient's lifetime; thus, progressive calcification over a period of years is not unusual. Ossification of the spinal ligaments has a specific site of predilection and often occurs in combination with senile ankylosing vertebral hyperostosis. Nevertheless, ossification of the spinal ligaments has been encountered in children with syndromic malformation complex. It is a multifactorial disease in which complex genetic and environmental factors interact, potentially leading to chronic pressure on the spinal cord and nerve roots with subsequent development of myeloradiculopathy. Our patient presented with a combination of achondroplasia, enchondroma-like metaphyseal dysplasia and calcification of the spinal ligaments. We suggest that the development of heterotopic bone formation along the spinal ligaments had occurred through an abnormal ossified enchondral mechanism. We postulate that ossification of the spinal ligaments and metaphyseal enchondromatous changes are related to each other and represent impaired terminal differentiation of chondrocytes in this particular case. Standard radiographic examination showed spinal bony ankylosis only. The pathological composites of the vertebrae have been clarified using scanning technology. Extensive spinal ligament ossification associated with calcification of the peripheral vertebral bodies and anterior end-plate irregularities were notable. We report what may be a novel spinal and extraspinal malformation complex in a girl with achondroplasia.</p

NSD1 mutations generate a genome-wide DNA methylation signature

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