ABSTRACT
S-adenosylhomocysteine hydrolase (AHCY) deficiency is a rare congenital disorder in methionine metabolism with minimal guidelines regarding anesthetic management. This case report describes a 19-year-old man presenting for a liver biopsy in interventional radiology due to a history of elevated aminotransferases and creatine kinase. He received dextrose-containing fluids and a total intravenous anesthetic to avoid rhabdomyolysis and hyperkalemia. Anesthetic goals for patients with AHCY deficiency should focus on avoiding rhabdomyolysis, minimizing postoperative ventilatory compromise, monitoring for potential coagulopathy, and providing anxiolysis.
Subject(s)
Amino Acid Metabolism, Inborn Errors , Anesthetics , Rhabdomyolysis , Amino Acid Metabolism, Inborn Errors/pathology , Glycine N-Methyltransferase/deficiency , Humans , Male , Young AdultABSTRACT
3q29 deletion syndrome (3q29del) is a recurrent deletion syndrome associated with neuropsychiatric disorders and congenital anomalies. Dysmorphic facial features have been described but not systematically characterized. This study aims to detail the 3q29del craniofacial phenotype and use a machine learning approach to categorize individuals with 3q29del through analysis of 2D photos. Detailed dysmorphology exam and 2D facial photos were ascertained from 31 individuals with 3q29del. Photos were used to train the next-generation phenotyping algorithm DeepGestalt (Face2Gene by FDNA, Inc, Boston, MA) to distinguish 3q29del cases from controls and all other recognized syndromes. Area under the curve of receiver operating characteristic curves (AUC-ROC) was used to determine the capacity of Face2Gene to identify 3q29del cases against controls. In this cohort, the most common observed craniofacial features were prominent forehead (48.4%), prominent nose tip (35.5%), and thin upper lip vermillion (25.8%). The FDNA technology showed an ability to distinguish cases from controls with an AUC-ROC value of 0.873 (p = 0.006) and led to the inclusion of 3q29del as one of the supported syndromes. This study found a recognizable facial pattern in 3q29del, as observed by trained clinical geneticists and next-generation phenotyping technology. These results expand the potential application of automated technology such as FDNA in identifying rare genetic syndromes, even when facial dysmorphology is subtle.
Subject(s)
Biological Variation, Population/genetics , Craniofacial Abnormalities/genetics , Genetic Predisposition to Disease , Intellectual Disability/genetics , Adolescent , Adult , Algorithms , Child , Child, Preschool , Chromosomes, Human, Pair 3/genetics , Craniofacial Abnormalities/pathology , Face , Female , Humans , Intellectual Disability/pathology , Male , Phenotype , Sequence Deletion/genetics , Young AdultABSTRACT
Background: Interstitial lung disease (ILD) has been recently reported in a few patients with pathogenic variants in the Filamin A (FLNA) gene with variable presentation and prognosis. This study evaluated the respiratory manifestations and clinical features in children with FLNA disease. Methods: We conducted a retrospective review of pediatric patients with variants in FLNA in a tertiary children's hospital. The clinical features, genotype, management, and outcomes were analyzed. Results: We identified 9 patients with variants in FLNA aged 15 months to 24 years, 4 females and 5 males. Six patients had abnormal chest imaging ranging from mild interstitial prominence to atelectasis, interstitial densities, and hyperinflation. Three patients with ILD presented during the neonatal period or early infancy with respiratory distress or respiratory failure requiring supplemental oxygen or assisted ventilation via tracheostomy. We report male twins with the same FLNA variant and lung disease, but different ages and clinical features at presentation eventually culminating in respiratory failure requiring assisted ventilation. All patients had FLNA variants identified by FLNA sequencing, had abnormal echocardiograms, and none of the patients underwent lung biopsy or lung transplantation. The outcomes were variable and could be as severe as chronic respiratory failure. Conclusion: The wide spectrum of respiratory manifestations and abnormal chest imaging in our study highlights the importance of evaluation for lung disease in patients with variants in FLNA. FLNA sequencing in suspected cases with ILD may obviate the need for a lung biopsy, prompt surveillance for progressive lung disease, and evaluation for associated clinical features.
Subject(s)
Filamins/genetics , Lung Diseases, Interstitial/genetics , Respiration, Artificial , Respiratory Insufficiency/genetics , Respiratory Insufficiency/therapy , Adolescent , Child , Child, Preschool , Dyspnea , Echocardiography , Female , Humans , Infant , Lung/pathology , Lung Diseases, Interstitial/diagnosis , Male , Mutation , Young AdultABSTRACT
We present three children from two unrelated families with Angelman syndrome (AS) whose developmental skills are far more advanced than any other non-mosaic AS individual ever reported. All have normal gait and use syntactic language spontaneously to express their needs. All of them have a c.2T > C (p.Met1Thr) variant in UBE3A, which abrogates the start codon of isoform 1, but not of isoforms 2 and 3. This variant was maternally inherited in one set of siblings, but de novo in the other child from the unrelated family. This report underscores the importance of considering AS in the differential diagnosis even in the presence of syntactic speech.
