Unusual radiographic progression of tumoral calcinosis along the anterior cruciate ligament in an adolescent male.

A 13-year-old boy was referred to orthopedic surgery for chronic intermittent pain and swelling of the left knee. Initial imaging was consistent with osteochondritis dissecans of the femoral condyle. Follow-up imaging demonstrated unexpected progression, with a mass extending into the notch, replacing the anterior cruciate ligament, and eroding the femoral and tibial condyles.

The Perfect Storm: A Case of Rapid-Onset Obesity With Hypoventilation, Hypothalamic, Autonomic Dysregulation, Neuroendocrine Tumor (ROHHADNET) With Heart Failure, Narcolepsy, and a Rare Location of a Pelvic Neuroendocrine Tumor.

Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare disease of concurrent respiratory dysfunction and autonomic dysregulation with endocrine abnormalities. ROHHADNET includes ROHHAD plus coexisting neuroendocrine tumors (NETs). We describe an eight-year-old boy, who originally presented at four years of age with rapid weight gain and hyperhidrosis and who developed mild obstructive sleep apnea (OSA).

Loss-of-function variants in cause a syndromic neurodevelopmental disorder.

Purpose: variants in (Cullin-3 ubiquitin ligase) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here we aimed to collect sporadic cases carrying rare variants in describe the genotype-phenotype correlation, and investigate the underlying pathogenic mechanism.

Methods: Genetic data and detailed clinical records were collected via multi-center collaboration.

Magnetic resonance imaging diagnosis of a skeletal dysplasia mimicking erosive arthropathy.

This case report of a 14-year-old boy with arthralgia and clinically suspected inflammatory arthropathy highlights how magnetic resonance imaging (MRI) ultimately diagnosed skeletal dysplasia. A genetic evaluation revealed a transient receptor potential vanilloid 4 (TRPV4) pathogenic variant. This is a rare description of the MRI appearance of this type of dysplasia in long bone epiphyses corresponding with the histological findings of disrupted endochondral ossification.

Protein modeling and clinical description of a novel in-frame GLB1 deletion causing GM1 gangliosidosis type II.

Background: Beta-galactosidase-1 (GLB1) is a lysosomal hydrolase that is responsible for breaking down specific glycoconjugates, particularly GM1 (monosialotetrahexosylganglioside). Pathogenic variants in GLB1 cause two different lysosomal storage disorders: GM1 gangliosidosis and mucopolysaccharidosis type IVB. In GM1 gangliosidosis, decreased β-galactosidase-1 enzymatic activity leads to the accumulation of GM1 gangliosides, predominantly within the CNS.

Novel Pathogenic Variant in TGFBR2 Confirmed by Molecular Modeling Is a Rare Cause of Loeys-Dietz Syndrome.

Loeys-Dietz syndrome (LDS) is a connective tissue disorder characterized by vascular findings of aneurysm and/or dissection of cerebral, thoracic, or abdominal arteries and skeletal findings. We report a case of a novel pathogenic variant in and phenotype consistent with classic LDS. The proband was a 10-year-old presenting to the genetics clinic with an enlarged aortic root (-scores 5-6), pectus excavatum, and congenital contractures of the right 2nd and 3rd digit.

Association of MTOR Mutations With Developmental Brain Disorders, Including Megalencephaly, Focal Cortical Dysplasia, and Pigmentary Mosaicism.

Importance: Focal cortical dysplasia (FCD), hemimegalencephaly, and megalencephaly constitute a spectrum of malformations of cortical development with shared neuropathologic features. These disorders are associated with significant childhood morbidity and mortality.

Objective: To identify the underlying molecular cause of FCD, hemimegalencephaly, and diffuse megalencephaly.

RASA1 somatic mutation and variable expressivity in capillary malformation/arteriovenous malformation (CM/AVM) syndrome.

Germline mutations in RASA1 are associated with capillary malformation-arteriovenous malformation (CM-AVM) syndrome. CM-AVM syndrome is characterized by multi-focal capillary malformations and arteriovenous malformations. Lymphatic anomalies have been proposed as part of the phenotype.

De novo nonsense mutations in KAT6A, a lysine acetyl-transferase gene, cause a syndrome including microcephaly and global developmental delay.

Chromatin remodeling through histone acetyltransferase (HAT) and histone deactylase (HDAC) enzymes affects fundamental cellular processes including the cell-cycle, cell differentiation, metabolism, and apoptosis. Nonsense mutations in genes that are involved in histone acetylation and deacetylation result in multiple congenital anomalies with most individuals displaying significant developmental delay, microcephaly and dysmorphism. Here, we report a syndrome caused by de novo heterozygous nonsense mutations in KAT6A (a.