Bi-allelic MYH3 loss-of-function variants cause a lethal form of contractures, pterygia, and spondylocarpotarsal fusion syndrome 1B.

Arthrogryposis is a consequence of reduced fetal movements and arises due to environmental factors or underlying genetic defects, with extensive genetic heterogeneity. In many instances, the genes responsible are involved in neuromuscular function. Missense variants in the gene encoding embryonic myosin heavy chain (MYH3) usually cause distal arthrogryposis. Recently, mono-allelic or bi-allelic MYH3 variants have been associated with contractures, pterygia, and spondylocarpotarsal fusion syndrome 1 (CPSFS1A and CPSFS1B). Here we describe three fetuses presenting in the second trimester with a lethal form of arthrogryposis and pterygia and harbouring bi-allelic variants in MYH3. One proband was compound heterozygous for a missense change and an extended splice site variant, a second proband had a homozygous frameshift variant, and a third proband was homozygous for a nonsense variant. Minigene assays performed on the first fetus showed that the missense and extended splice site variants resulted in aberrant splicing, likely resulting in near complete loss of full-length MYH3 transcript. This study shows that loss of MYH3 is associated with a lethal arthrogryposis phenotype and highlights the utility of minigene assays to assess splicing.

Iron Pill-Induced Gastritis in the Paediatric Population.

Iron is the most common trace mineral in the body. The effects of iatrogenic iron pill-induced gastritis (IPIG) at therapeutic levels are underreported and underappreciated in the paediatric population. Herein, we report a case of an 11-year-old boy presenting with increasing epigastric pain and refusing oral intake secondary to iron pill tablets. We report only the second confirmed case of a paediatric patient with IPIG in the peer-reviewed literature.

Mullerian carcinosarcoma arising in the cecum associated with florid vascular proliferation/glomeruloid microvascular proliferation.

Angiogenesis is required for tumor growth, and the degree of new vessel formation correlates with adverse prognosis in many types of malignancies. It has now been appreciated that tumor-associated vasculature is heterogenous and sometimes includes a complex vasoformative process that has been termed florid vascular proliferation or glomeruloid microvascular proliferation. These vascular lesions are most characteristic of high-grade gliomas and neuroendocrine tumors but are being increasingly recognized in other types of neoplasias as well. Herein we report a case of carcinosarcoma arising within the cecal wall of a 62-yr-old patient that exhibited florid vascular proliferation, particularly at the time of peritoneal recurrence. Recognition of these tumor-associated vasoformative lesions may be important in view of their adverse prognostic association and may become therapeutically relevant considering the current developments in angiogenesis inhibitors.

Fibrolipomatous hamartoma of the median nerve in the elbow: a case report.

A fibrolipomatous hamartoma-also known as a fibrofatty overgrowth, perineural lipoma, intraneural lipoma, and lipomatous hamartoma-is a rare, benign, congenital lesion most commonly found in the median nerve, usually at the level of the wrist or hand. To our knowledge, no published cases report a hamartoma arising from the median nerve at the level of the elbow. We report a case of a fibrolipomatous hamartoma in a 55-year-old woman that necessitated a surgical intervention because of its size and associated neurologic symptoms.