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Genes (Basel) 2021 May 23;12(6). Epub 2021 May 23.

Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.

Latent transforming growth factor β (TGFβ)-binding protein (LTBP) 4, a member of the LTBP family, shows structural homology with fibrillins. Both these protein types are characterized by calcium-binding epidermal growth factor-like repeats interspersed with 8-cysteine domains. Based on its domain composition and distribution, LTBP4 is thought to adopt an extended structure, facilitating the linear deposition of tropoelastin onto microfibrils. Read More

Clin Chim Acta 2021 Aug 20;519:285-290. Epub 2021 May 20.

AP-HP, Biochimie Métabolique et Cellulaire, Hôpital Bichat-Claude Bernard, Paris, France; INSERM UMR1193, Mécanismes cellulaires et moléculaires de l'adaptation au stress et cancérogenèse, Université Paris-Sud, Châtenay-Malabry, France. Electronic address:

We identified three cases of congenital disorders of glycosylation (CDG) with Golgi homeostasis disruption, one ATP6V0A2-CDG and two COG4-CDG, with normal transferrin screening analyses. Patient 1 (P1) presented at birth with cutis laxa. Patient 2 (P2) and patient 3 (P3) are adult siblings and presented with severe symptoms evocative of inborn errors of metabolism. Read More

Am J Hum Genet 2021 Jun 14;108(6):1095-1114. Epub 2021 May 14.

Center for Medical Genetics Ghent, Ghent University Hospital, Ghent 9000, Belgium; Department of Biomolecular Medicine, Ghent University, Ghent 9000, Belgium. Electronic address:

Latent transforming growth factor β (TGFβ)-binding proteins (LTBPs) are microfibril-associated proteins essential for anchoring TGFβ in the extracellular matrix (ECM) as well as for correct assembly of ECM components. Variants in LTBP2, LTBP3, and LTBP4 have been identified in several autosomal recessive Mendelian disorders with skeletal abnormalities with or without impaired development of elastin-rich tissues. Thus far, the human phenotype associated with LTBP1 deficiency has remained enigmatic. Read More

Hum Mutat 2021 May 11. Epub 2021 May 11.

Flinders Department of Ophthalmology, College of Medicine and Public Health, Flinders University, Bedford Park, South Australia, Australia.

Gelsolin (GSN) variants have been implicated in amyloidosis of the Finnish type. This case series reports a novel GSN:c.1477T>C,p. Read More

J Med Case Rep 2021 Apr 29;15(1):248. Epub 2021 Apr 29.

Ophthalmology Unit, Humanitas Research Hospital, Rozzano, Milan, Italy.

Background: Dermatochalasis of the upper eyelids (blepharochalasis) is a typical age-related change in the upper third of the face and a major concern for facial aesthetics. Nowadays both surgical and nonsurgical interventions are available for patients complaining of upper eyelid dermatochalasis. Although nonsurgical treatments are often easier to perform, if they are not performed correctly, complications may ensue and worsen the condition. Read More

Yonsei Med J 2021 May;62(5):431-438

Department of Neurology, Rehabilitation Institute of Neuromuscular Disease, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.

Purpose: AGel amyloidosis is systemic amyloidosis caused by pathogenic variants in the GSN gene. In this study, we sought to characterize the clinical and brain magnetic resonance image (MRI) features of Korean patients with AGel amyloidosis.

Materials And Methods: We examined 13 patients with AGel amyloidosis from three unrelated families. Read More

Facial Plast Surg Clin North Am 2021 May 24;29(2):179-193. Epub 2021 Apr 24.

W Aesthetic Plastic Surgery, 06 - 28/29, Mount Elizabeth Novena Specialist Center, 38 Irrawaddy Road, Singapore 329563, Singapore.

Given the central importance of the "eyes," meaning the periorbital region, to facial appearance, the motivated blepharoplasty patient has the opportunity to improve appearance significantly beyond the minimum of age reversal, to reveal inner beauty or add attractiveness. Bright and beautiful eyes have good three-dimensional contouring. The benefits of a quality eyelid crease enable the surgical focus to be on lid contouring with a reduced requirement for lid skin and fat excision. Read More

Clin Genet 2021 Apr 18. Epub 2021 Apr 18.

Genetic Services of Western Australia, King Edward Memorial Hospital, Perth, Western Australia, Australia.

We report three babies from two families with a severe lethal form of congenital cutis laxa. All three had redundant and doughy-textured skin and two siblings from one family had facial dysmorphism. Echocardiograms showed thickened and poorly contractile hearts, arterial dilatation and tortuosity. Read More

Genes (Basel) 2021 Mar 31;12(4). Epub 2021 Mar 31.

Center for Medical Genetics Ghent, Ghent University Hospital, 9000 Ghent, Belgium.

Hereditary disorders of connective tissue (HDCT) compromise a heterogeneous group of diseases caused by pathogenic variants in genes encoding different components of the extracellular matrix and characterized by pleiotropic manifestations, mainly affecting the cutaneous, cardiovascular, and musculoskeletal systems. We report the case of a 9-year-old boy with a discernible connective tissue disorder characterized by cutis laxa (CL) and multiple herniations and caused by biallelic loss-of-function variants in . Hence, we identified as a novel disease-causing gene in the CL spectrum, differentiating it from other HDCT. Read More

Rev Prat 2020 11;70(9):991-992

Association Cutis laxa internationale, Bons-en-Chablais (74), France.

Genetics 2021 May;218(1)

The Jackson Laboratory, Bar Harbor, ME 04609, USA.

The final step in proline biosynthesis is catalyzed by three pyrroline-5-carboxylate reductases, PYCR1, PYCR2, and PYCR3, which convert pyrroline-5-carboxylate (P5C) to proline. Mutations in human PYCR1 and ALDH18A1 (P5C Synthetase) cause Cutis Laxa (CL), whereas mutations in PYCR2 cause hypomyelinating leukodystrophy 10 (HLD10). Here, we investigated the genetics of Pycr1 and Pycr2 in mice. Read More

Plast Reconstr Surg 2021 Mar;147(3):604-607

From the Division of Ophthalmology Paediatric and Oculoplastic Surgery, Department of Ophthalmology, University Hospital of Bordeaux Pellegrin; and Jamison Street Specialist Center.

Summary: Subbrow blepharoplasty is widely used in Asian patient populations to preserve the natural upper lid crease while addressing dermatochalasis with lateral hooding. The authors describe the first use of this technique in Caucasians with dermatochalasis and lateral hooding. This is a retrospective case series of Caucasian patients who underwent subbrow blepharoplasty for moderate to severe dermatochalasis with lateral hooding. Read More

Vestn Oftalmol 2021 ;137(1):102-105

I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.

Floppy eyelid syndrome is rarely diagnosed nowadays. Most patients remain without the correct diagnosis for a long time, which means they do not receive adequate treatment. This syndrome is known to be accompanied by many concomitant clinical manifestations complicating the diagnostic search. Read More

J Plast Reconstr Aesthet Surg 2021 Feb 10. Epub 2021 Feb 10.

School of Medicine, European University Cyprus, Nicosia, Cyprus; Ophthalmos Research and Educational Institute, Nicosia, Cyprus.

BMC Neurol 2021 Feb 11;21(1):64. Epub 2021 Feb 11.

Department of Neurology, Graduate School of Medical Sciences, University of Yamanashi, Yamanashi, 409-3898, Japan.

Background: ALDH18A1 mutations lead to delta-1-pyrroline-5-carboxylate-synthetase (P5CS) deficiency, which is a urea cycle-related disorder including SPG9A, SPG9B, autosomal dominant cutis laxa-3 (ADCL3), and autosomal recessive cutis laxa type 3A (ARCL3A). These diseases exhibit a broad clinical spectrum, which makes the diagnosis of P5CS deficiency difficult. We report here a rare Japanese family including both patients with an ALDH18A1 mutation (SPG9A) and ones with CMT1A. Read More

Ann Plast Surg 2021 03;86(3):340-344

Eye Research Center, The Five Senses Institute.

Objectives: Three prior studies (2008, 2011, 2018) histopathologically compared the eyelid specimens of patients with dermatochalasis (DC, undergoing blepharoplasty) with a control group and proposed that DC may begin with subclinical inflammation leading to elastolysis and lymphostasis. With growing number of younger patients consulting for blepharoplasty, the unanswered question is whether histopathologic changes of DC differ between the younger and the older.

Patients And Methods: In this prospective case series, 20 right upper eyelid skin of 20 nonsmoker, class 3 Fitzpatrik skin type women (30-68 years old) were histopathologically examined. Read More

J Craniofac Surg 2021 Jan 28. Epub 2021 Jan 28.

Eye Hospital of Wenzhou Medical University, Wenzhou, China Sydney Hospital and Sydney Eye Hospital, Sydney, NSW, Australia.

Background: Conventional assessment of the height of upper eyelid skin excision in dermatochalasis correction is performed with patient's eyes closed in supine position. It is not able to consider the effects of gravity on the upper eyelid, thus may lead to asymmetric postoperative appearance. The authors herein report a novel preoperative upright design (PUD) that can accurately determine the amount of skin excision with patients' eyes open in dermatochalasis correction. Read More

J Cosmet Dermatol 2021 Feb 1. Epub 2021 Feb 1.

Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.

Background: Skin aging is an inevitable phenomenon characterized by wrinkled skin and loss of elasticity. To date, several studies have been performed on skin aging to discover the underlying mechanisms and improve efficient preventive strategies and anti-aging therapeutics.

Aims: Here, we aimed to investigate the modifications of oxidative phosphorylation and glycolysis which are the critical determinants of aging in aged-phenotype skin. Read More

Facial Plast Surg 2021 Apr 31;37(2):194-197. Epub 2021 Jan 31.

Department of Otolaryngology, Head and Neck Surgery, Northwestern Medical Group, Chicago, Illinois.

Upper eyelid surgery is a common procedure performed by a variety of subspecialists including facial plastic surgeons, oculoplastic surgeons, general otolaryngologists, and plastic surgeons. Traditionally, a skin incision is marked in the preoperative setting to allow for an excision that eliminates upper eyelid hooding while preventing lagophthalmos. Many different methodologies have been proposed to maximize results and minimize complications. Read More

Orphanet J Rare Dis 2021 01 28;16(1):51. Epub 2021 Jan 28.

Department of Medical Genetics, Tabriz University of Medical Sciences, Tabriz, Iran.

Background: FBLN5-related cutis laxa (CL) is a rare disorder that involves elastic fiber-enriched tissues and is characterized by lax skin and variable systemic involvement such as pulmonary emphysema, arterial involvement, inguinal hernias, hollow viscus diverticula and pyloric stenosis. This type of CL follows mostly autosomal recessive (AR) and less commonly autosomal dominant patterns of inheritance.

Results: In this study, we detected a novel homozygous missense variant in exon 6 of FBLN5 gene (c. Read More

Int J Mol Sci 2021 Jan 22;22(3). Epub 2021 Jan 22.

Eye Hospital, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.

Gelsolin amyloidosis typically presents with corneal lattice dystrophy and is most frequently associated with pathogenic variant p.Asp214Asn. Here we report clinical and histopathological features of gelsolin amyloidosis associated with a novel variant p. Read More

Klin Monbl Augenheilkd 2021 Jan 14;238(1):33-40. Epub 2021 Jan 14.

Augenklinik, Klinikum der Universität München, Deutschland.

Patients with Graves' orbitopathy often develop eyelid changes. These may be the result of a volume effect or a malposition. Both dermatochalasis with fat tissue increase and eyelid retraction may lead to functional or aesthetic impairment. Read More

J Transl Autoimmun 2021 20;4:100077. Epub 2020 Dec 20.

Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, CA, USA.

Ehlers-Danlos Syndrome (EDS) is a family of multisystemic hereditary connective tissue disorders now comprised of 13 recognized subtypes, classical, classical-like, cardiac-valvular, vascular, hypermobile, arthrochlasia, dermosparaxis, kyphoscoliotic, brittle cornea syndrome, spondylodysplastic, musculocontractural, myopathic, and periodontal, as designated by the most recent 2017 International classification system. Clinical presentation of this disease can range from mild manifestations including skin hyperextensibility and joint hypermobility, to more severe complications such as vascular and organ rupture. While there may be accompanying inflammation in some of the subtypes of EDS, the pathogenic mechanisms have not been clearly defined. Read More

Turk J Ophthalmol 2020 12;50(6):356-361

Ege University Faculty of Medicine, Department of Chest Diseases, İzmir, Turkey.

Objectives: To evaluate periorbital tissue alterations including eyelid laxity and eyelash ptosis in patients with obstructive sleep apnea syndrome (OSAS).

Materials And Methods: Based on polysomnography, 96 eyes of 48 patients with moderate/severe OSAS (Group 1) and 44 eyes of 22 patients with simple snoring (Group 2) were enrolled. Comprehensive eye examination along with eyelid laxity measurements including vertical and anterior distraction, presence of dermatochalasis, interpalpebral distance, and levator function were assessed. Read More

Am J Med Genet A 2021 03 27;185(3):955-965. Epub 2020 Dec 27.

Division of Medical Genetics, Fondazione IRCCS-Casa Sollievo della Sofferenza, Foggia, Italy.

ATP6V0A2-related cutis laxa, also known as autosomal recessive cutis laxa type 2A (ARCL2A), is a subtype of hereditary cutis laxa originally characterized by skin, skeletal, and neurological involvement, and a combined defect of N-glycosylation and O-glycosylation. The associated clinical spectrum subsequently expanded to a less severe phenotype dominated by cutaneous involvement. At the moment, ARCL2A was described in a few case reports and series only. Read More

Appl Clin Genet 2020 17;13:233-240. Epub 2020 Dec 17.

Laboratorio de Biología Molecular y Pruebas Diagnósticas de Alta Complejidad, Fundación Cardioinfantil-Instituto de Cardiología, Bogotá, Colombia.

The gene encodes elastin, a fundamental protein of the extracellular matrix that confers elasticity to different tissues including blood vessels. The formation of elastin fibers is a complex process involving monomer coacervation and subsequent crosslinking. Mutations in exons 1-29 of the gene have been linked to supravalvular aortic stenosis (SVAS) whereas mutations in exons 30-33 are associated with autosomal dominant cutis laxa (ADCL). Read More

Clin Ter 2021 Jan-Feb;171(1):e4-e7

Department of Orthopaedic and Traumatology, Policlinico Umberto I Hospital-Sapienza University of Rome.

De Barsy syndrome is an autosomal recessive condition characterized by an progeroid appearance with distinctive facial features and cutis laxa. Ophthalmological, orthopedic, and neurological anomalies are generally also present. This syndrome is rare and the complex therapeutic management, from a surgical but also rehabilitative point of view, has not been recognized. Read More

J Inherit Metab Dis 2020 Dec 15. Epub 2020 Dec 15.

Institut für Medizinische Genetik und Humangenetik, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

Several inborn errors of metabolism show cutis laxa as a highly recognizable feature. One group of these metabolic cutis laxa conditions is autosomal recessive cutis laxa type 2 caused by defects in v-ATPase components or the mitochondrial proline cycle. Besides cutis laxa, muscular hypotonia and cardiac abnormalities are hallmarks of autosomal recessive cutis laxa type 2D (ARCL2D) due to pathogenic variants in ATP6V1A encoding subunit A of the v-ATPase. Read More