Michael Marble

Report of a new patient with transposition of the great arteries with deletion of 22q11.2

We report on a new patient with d-transposition of the great arteries who was found to have deletion of 22q11.2. He had minor facial anomalies, normal T- and B-cell subsets, and transient hypocalcemia. Similar to rare previous reports, our patients extracardiac manifestations were relatively mild.

Monosomy 18p and immunologic dysfunction: review of the literature and a new case report with thyroiditis, IgA deficiency, and systemic lupus erythematosus.

Departments of Pathology, Pediatrics, Division of Clinical Genetics, Department of Pediatrics, Division of Rheumatology, Louisiana State University, Health Sciences Center and Children’s Hospital of New Orleans, New Orleans, Louisiana, USA Correspondence to Robin R. McGoey, MD, Department of Pathology, Louisiana State University, Health Sciences Center, 1901 Perdido Street, New Orleans, Louisiana 70112, USA Tel: + 1 504 568 6031; fax: + 1 504 568 6037; e-mail: rmcgoe@lsuhsc.edu

Phenotypic features of a boy with trisomy of 16q22-->qter due to paternal Y; 16 translocation.

We report on the phenotypic features of a patient with partial trisomy of the long arm of chromosome 16 due to an unbalanced Y;16 translocation (46,X,der[Y]t[Y;16] [q12;q22]pat). The patient was noted to have craniofacial anomalies and developmental delay, but no other major malformations. The father, a balanced Y;16 translocation carrier, has apparently normal fertility.

RAF1 variants causing biventricular hypertrophic cardiomyopathy in two preterm infants: further phenotypic delineation and review of literature

Noonan syndrome (NS) is an autosomal dominant disorder characterized by distinctive facial features, short neck, short stature, congenital heart defects, pectus deformities, and variable developmental delays. NS is genetically heterogeneous as pathogenic variants in several genes involved in the Ras/mitogen-activated protein kinase pathway have been associated with a NS phenotype. Overall, 50% of patients harbor pathogenic variants in PTPN11, whereas 3-17% of patients have variants in RAF1. We present two premature neonates with progressive biventricular hypertrophy found to have RAF1 variants in the CR2 domain. Molecular testing in patient 1 revealed a missense variant of a highly conserved residue c.782 C>G (p.P261R). This variant has been reported once with fatal outcome. Patient 2 also had a missense variant in a highly conserved neighboring residue c.770 C>T (p.S257L). This variant has been previously reported, most recently associated with the development of pulmonary arterial hypertension. Both our patients had prenatal findings of polyhydramnios, short long bones, hydrops fetalis, and cardiac anomalies with progressive biventricular hypertrophic cardiomyopathy. Both patients had a lethal outcome. Our findings further support the pathogenicity and lethality of p.P261R, and the need to monitor for pulmonary arterial hypertension in p.S257L. In addition, the second patient was presented with progressive hydrocephalus due to aqueductal stenosis. This could be related to the NS phenotype. More cases with this association are needed to confirm this finding.

Bilateral absence of the ulna in 4q terminal deletion syndrome: evidence for a critical region.

Louisiana State University Health Sciences Center, School of Medicine, Department of Pediatrics, Louisiana State University Health Sciences Center, Division of Neonatology and Department of Pediatrics, Louisiana State University Health Sciences Center, Division of Clinical Genetics, Children’s Hospital of New Orleans, New Orleans, Louisiana, USA Correspondence to Michael Marble, MD, Department of Pediatrics, Louisiana State University Health Sciences Center, Division of Clinical Genetics, Children’s Hospital of New Orleans, 200 Henry Clay Avenue, New Orleans, LA 70118, USA Tel: + 1 504 896 9254; fax: + 1 504 896 3997; e-mail: mmarbl1@lsuhsc.edu

45,X/47,XX,+18 and ring (18) mosaicism with mild phenotypic features including normal stature: clinical report and review of the literature.

Departments of Pathology, Pediatrics, Division of Clinical Genetics, Louisiana State University Health Sciences Center, Children’s Hospital of New Orleans, New Orleans, Louisiana and Department of Pediatrics, Weisskopf Child Evaluation Center, University of Louisville, Louisville, Kentucky, USA Correspondence to Robin R. McGoey, MD, Department of Genetics, Children’s Hospital of New Orleans, 200 Henry Clay Avenue, New Orleans, LA 70118, USA Tel: + 1 504 568 6031; e-mail: rmcgoe@lsuhsc.edu

Transposition of the great arteries and hypocalcemia in a patient with fetal hydantoin syndrome

We report a patient with fetal hydantoin syndrome (FHS) with associated d-transposition of the great arteries (d-TGA) and persistent hypocalcemia. d-TGA and hypocalcemia have each been individually reported once in association with FHS, but these patients were also prenatally exposed to phenobarbital. To our knowledge, this is the first report of these problems occurring after prenatal exposure to hydantoin alone. The combination of congenital heart disease and hypocalcemia in our patient raises the possibility of a hydantoin effect on neural crest migration.

Delayed diagnosis of a patient with Usher syndrome 1C in a Louisiana Acadian family highlights the necessity of timely genetic testing for the diagnosis and management of congenital hearing loss

Advances in sequencing technologies and increased understanding of the contribution of genetics to congenital sensorineural hearing loss have led to vastly improved outcomes for patients and their families. Next-generation sequencing and diagnostic panels have become increasingly reliable and less expensive for clinical use. Despite these developments, the diagnosis of genetic sensorineural hearing loss still presents challenges for healthcare providers. Inherited sensorineural hearing loss has high levels of genetic heterogeneity and variable expressivity. Additionally, syndromic hearing loss (hearing loss and additional clinical abnormalities) should be distinguished from non-syndromic (hearing loss is the only clinical symptom). Although the diagnosis of genetic sensorineural hearing loss can be challenging, the patient’s family history and ethnicity may provide critical information, as certain genetic mutations are more common in specific ethnic populations. The early identification of the cause of deafness can benefit patients and their families by estimating recurrence risks for future family planning and offering the proper interventions to improve their quality of life. Collaboration between pediatricians, audiologists, otolaryngologists, geneticists, and other specialists are essential in the diagnosis and management of patients with hearing disorders. An early diagnosis is vital for proper management and care, as some clinical manifestations of syndromic sensorineural hearing loss are not apparent at birth and have a delayed age of onset. We present a case of Usher syndrome (congenital deafness and childhood-onset blindness) illustrating the challenges encountered in the diagnosis and management of children presenting with congenital genetic sensorineural hearing loss, along with helpful resources for clinicians and families.

Valproate-induced hyperammonemic coma in females with unrecognized partial ornithine transcarbamylase deficiency

A female child with undiagnosed partial ornithine transcarbamylase deficiency suffered hyperammonemic coma after initiation of valproate for suspected seizures. Retrospec tive history and metabolic testing indicated ornithine tra nscarbamylase deficiency. This case, along with previous reports in childr en and adults, demonstrates the importance of a focused history and consideration of appropriate metabolic testing prior to im plementation of valproate therapy especially in female patients.