Fibrillin-1, an extracellular matrix (ECM) protein encoded by the FBN1 gene, serves as a microfibril scaffold crucial for elastic fiber formation and homeostasis in pliable tissue such as the skin. Aside from causing Marfan syndrome, some mutations in FBN1 result in scleroderma, marked by hardened and thicker skin which limits joint mobility. Here, we describe a tight skin phenotype in the Fbn1G234D/G234D mice carrying a corresponding variant of FBN1 in the hybrid1 domain that was identified in a patient with familial aortic dissection. Unlike scleroderma, skin thickness and collagen fiber abundance do not change in the Fbn1G234D/G234D mutant skin. Instead, increased collagen cross-links were observed. In addition, short elastic fibers were sparsely located underneath the panniculus muscle layer, and an abundance of thin, aberrant elastic fibers was increased within the subcutaneous fascia, which may have tightened skin attachment to the underlying skeletal muscle. Structurally, Fbn1G234D/G234D microfibrils have a disrupted shoulder region that shares similarities with hybrid1 deletion mutant microfibrils. We then demonstrate the consequence of fibrillin-1 G234D mutation on dermal fibroblast functions. Mutant primary fibroblasts produce fewer elastic fibers, exhibit slower migration and increased cell stiffness. Moreover, secretome from mutant fibroblasts are marked by enhanced secretion of ECM, ECM-modifying enzymes, proteoglycans and cytokines, which are pro-tissue repair/fibrogenic. The transcriptome of mutant fibroblasts displays an increased expression of myogenic developmental and immune-related genes. Our study proposes that imbalanced ECM homeostasis due to a fibrillin-1 G234D mutation impacts fibroblast properties with potential ramifications on skin function.

Iris cysts are uncommon lesions, most of them are iris pigment epithelial (IPE) cysts which typically manifest in adults as unilateral single cysts, are typically asymptomatic and rarely require treatment. The most frequent location of IPE cysts is the iris periphery and the iridociliary sulcus, whereas pupillary cysts are rare. This observational case series aims to describe a unique occurrence of bilateral pupillary IPE cysts in three consecutive generations of a single family. The series describes eight patients of a single family with no consanguineous marriage. All patients have IPE cysts with remarkable abnormally-shaped pupils. The patients were examined at the slit-lamp and imaged with anterior segment optical coherence tomography. Three brothers (14, 19 and 28 years old) were symptomatic and suffered from hemeralopia and reduced visual acuity. ND-YAG laser was successful in relieving the symptoms in the two younger brothers. No recurrence or refill of the cysts occurred after laser application and no intra- or ppostoperative complications were observed during a 9-month follow-up. The older family members showed spontaneously shrunken IPE cysts. IPE cysts are considered idiopathic with an unclear origin. The rare familial incidence of the cysts suggests an autosomal dominant heredity pattern. Many theories were proposed to explain the origin of cysts and none is conclusive. Their principal clinical significance is their similarity to pigmented iris tumors, but they might also cause visual symptoms. Treatment modalities vary from less invasive chemical compounds and ND: YAG laser application to more invasive surgical procedures with disparate efficacy and safety. In the case of multiple cysts, examination of other family members is worthy even when asymptomatic and cardiac consultation of affected patients is warranted as IPE cysts may proclaim a coexisting cardiovascular abnormality, such as familial aortic dissection.

This case report details familial aortic dissection in 2 second-degree blood relatives who experienced sudden aortic dissections. One patient underwent emergency computed tomography angiography (CTA) and the other underwent magnetic resonance angiography (MRA). These imaging examinations were instrumental in revealing each patient's condition. One patient died of dissection rupture while being prepped for surgery. The other patient underwent surgery, recovered, and undergoes continual monitoring for the condition. A positive family history of aortic dissection should be considered in patients presenting with aortic emergencies. Many genes can contribute to this condition, with most genes relating to smooth muscle and connective tissue disorders. Imaging studies for evaluating and monitoring aortic dissection include transesophageal echocardiography, CTA, and MRA. Surgical treatment is possible for aortic dissection, with the goals being to stabilize the dissection and reduce the possibility of rupture. The mortality rate for aortic dissection is high, with the main cause of death being dissection rupture. Lifelong monitoring of survivors and first-degree relatives is recommended.

Current guidelines on the management of thoracic aortic disease recommend that the ascending aorta be replaced when it reaches the size of 5.5 cm. Recently emerging data suggest that this criterion may need to be shifted to the left, signifying a recommendation to operate on patients with smaller aortic sizes. The data that support the need for a leftward shift in the guidelines include (1) novel and more granular data on the natural history of ascending aortic aneurysm between 5 and 6 cm showing that 2 hinge risk points exist-one at 5.25 cm, and the other at 5.75 cm; (2) aortic diameter before the moment of aortic dissection is at least 7 mm smaller than postdissection aortic size; (3) the advent of a semiautomated centerline method of imaging assessment seems to underestimate true ascending aortic size; (4) aortic surgery in the present era is very safe and its benefits outweigh the associated risks; (5) genetic testing via high-throughput next-generation sequencing identifies genetic defects responsible for aortic catastrophes at smaller aortic sizes; and (6) familial aortic dissection occurrence suggests that family members of an aortic dissection victim who harbor a sizable aneurysm should be operated on regardless of aortic size.