Novel truncating and missense variants extending the spectrum of EMC1-related phenotypes, causing autism spectrum disorder, severe global development delay and visual impairment.

We report a ten-year-old boy, born to unrelated parents, with early-onset severe global development delay due to novel EMC1 biallelic pathogenic variants. A truncating variant, p.(Tyr378*) and a missense variant, p.(Phe953Ser), located in exon 11 and 23 of EMC1 gene respectively, have been found by reanalysis of exome sequencing data. The proband's phenotype included several signs that overlap with the phenotype of previously reported patients, associating severe global developmental delay, abnormal ophthalmological examination, and postnatal slow-down of the head circumference growth. Some distinguishing clinical signs were observed in comparison to patients from literature, such as autism spectrum disorder, absence of seizures, scoliosis or facial dysmorphic features, thus extending the spectrum of EMC1-related phenotypes. Similarly, brain MRI, performed at 2 years, showed normal cerebellar volume and structure, whereas cerebellar atrophy was described in literature. Moreover, difficulties of clinical differential diagnosis between EMC1-associated disease and other etiologies of global development delay support the importance of large-scale genetic investigations. Our diagnostic approach, through reanalysis of exome sequencing data, highlights the importance of reconsidering initial negative results for patients with a strong suspicion of genetic disease, and to update analytic pipelines in order to improve the diagnostic yield of exome sequencing. PMID: 32092440 [PubM...
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research

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Use of the Microcuff® During General Anesthesia for Patients With Scoliosis. Anesth Prog. 2020;67(1):23-27 Authors: Kishimoto T, Hayashi S, Nakanishi Y, Goto T, Kosugi K, Sakurai S Abstract Scoliosis may often be associated with a variety of cardiovascular and respiratory conditions or diseases, and depending on the severity of the spinal deformity, it may also complicate anesthetic management because of the difficulty of neck extension and tracheal deformity. Therefore, patients with scoliosis may require careful perioperative anesthetic considerations. A 14-year-old girl was scheduled to undergo ...
Source: Anesthesia Progress - Category: Anesthesiology Tags: Anesth Prog Source Type: research
Background: Opioids are commonly used after posterior spinal instrumented fusion (PSIF) for adolescent idiopathic scoliosis (AIS). Prescription opioids use can potentially lead to misuse, abuse, dependence, and overdose death. Prolonged opioid use has not been extensively studied in the postoperative AIS population. The purpose of this study is to identify risk factors associated with prolonged opioid use after PSIF for AIS. Methods: A large insurance database was queried for AIS patients undergoing PSIF. Patients with prolonged postoperative opioid use were defined as those receiving new prescriptions for an opioid m...
Source: Journal of Pediatric Orthopaedics - Category: Orthopaedics Tags: Scoliosis Source Type: research
Rubinstein–Taybi syndrome (RSTS) is a rare dominant disorder with intellectual disability, postnatal growth deficiency, and multiple congenital anomalies. Approximately 50–70% of the patients have a mutation in the CREBBP gene (RSTS1) and 5–10% display an EP300 gene mutation (RSTS2). Craniospinal abnormalities such as microcranium, scoliosis, and lordosis are frequent findings in RSTS1, but malformations of the brain or spinal cord are seen only occasionally. Here, we report on a 3-year-old boy with facial abnormalities of RSTS, broad thumbs and halluces, developmental delay, autistic features, cerebellar...
Source: Clinical Dysmorphology - Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
American Journal of Medical Genetics Part A, EarlyView.
Source: American Journal of Medical Genetics Part A - Category: Genetics & Stem Cells Authors: Source Type: research
Semin Hear 2018; 39: 321-333 DOI: 10.1055/s-0038-1666821This perspective explores common pediatric diagnoses that could present with central vestibular pathway dysfunction, leading to delays in motor development and postural control, and gaze instability. Specifically, the following diagnoses are considered: cerebral palsy, myelomeningocele, vestibular migraine, attention-deficit hyperactivity disorder, developmental coordination disorder, concussion, childhood cancer, congenital muscular torticollis, adolescent idiopathic scoliosis, and autism. Suggestions for clinical screening, vestibular function testing, and vestibula...
Source: Seminars in Hearing - Category: Audiology Authors: Tags: Review Article Source Type: research
Abstract De novo variants of ASH1L, which encodes a histone methyltransferase, have been reported in a few patients with intellectual disability and autistic features. Here, we identified a novel de novo frame-shift variant, c.2422_2423delAAinsT which predicts p.(Lys808TyrfsTer40), in ASH1L in a patient with multiple congenital anomalies (MCA), fine motor developmental delay, learning difficulties, attention deficit hyperactivity disorder, sleep apnea, and scoliosis. This frame-shift variant is expected to result in loss-of-function. Our report provides further evidence to support loss-of-function alterations of A...
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research
We present a 7-year old male with severe delays, hypotonia and dysmorphic features who had striking, deep palmar and plantar creases and pillowing of the soft tissues of the palms and soles. His facial features included a high anterior hairline, small eyes with narrowed palpebral fissures, a bulbous nasal tip with a short columella, and a large mouth with a thin upper vermilion, and small chin. He had a submucous cleft palate, bilateral cryptorchidism and hydronephrosis. Cranial imaging demonstrated an Arnold Chiari malformation that was also present in his maternal uncle by report. Exome sequencing revealed a de novo hete...
Source: European Journal of Medical Genetics - Category: Genetics & Stem Cells Authors: Tags: Eur J Med Genet Source Type: research
ConclusionsMotor problems are among the most common comorbid developmental problems in children with NF1, and these problems do not diminish with age. Because of their impact on daily functioning, motor problems need to be specifically addressed in diagnosis, follow-up, and treatment of NF1.
Source: Journal of Neurodevelopmental Disorders - Category: Neurology Source Type: research
Books are great tools for teaching empathy to children. They can help kids understand what it’s like to walk in someone else’s shoes — someone with a physical or mental disability, chronic illness or learning difference. They can also help kids with medical issues see how other kids cope — which can be validating or even help spark new ideas. And books help younger generations recognize that no matter what obstacle they may face, they’re still just kids, and they’re not alone. Today, many children’s book authors are weaving characters with me...
Source: Thrive, Children's Hospital Boston - Category: Pediatrics Authors: Tags: Parenting autism cerebral palsy craniofacial anomaly scoliosis Source Type: news
Rubinstein–Taybi syndrome (RTS) is an autosomal dominant neurodevelopmental disorder characterized by growth deficiency, broad thumbs and great toes, intellectual disability and characteristic craniofacial appearance. Mutations in CREBBP account for around 55% of cases, with a further 8% attributed to the paralogous gene EP300. Comparatively few reports exist describing the phenotype of Rubinstein–Taybi because of EP300 mutations. Clinical and genetic data were obtained from nine patients from the UK and Ireland with pathogenic EP300 mutations, identified either by targeted testing or by exome sequencing. All p...
Source: Clinical Dysmorphology - Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
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