Expanding the Spectrum of Neurological Manifestations in Cutis Laxa, Autosomal Recessive, Type IIIA.

Cutis laxa is a heterogeneous group of diseases, characterized by abundant and wrinkled skin and a variable degree of intellectual disability. Cutis laxa, autosomal recessive, type IIIA and autosomal dominant 3 syndromes are caused by autosomal recessive or de novo pathogenic variants in ALDH18A1. Autosomal recessive variants are known to lead to the most severe neurological phenotype, and very few patients have been described.We describe a 13-month-old patient with cutis laxa, autosomal recessive, type IIIA, with an extremely severe phenotype, including novel neurological findings. This description enlarges the neurological spectrum associated to cutis laxa, autosomal recessive, type IIIA, and provides an additional description of this syndrome.

Cutis Laxa.

Cutis laxa is an inherited or acquired disease characterized by redundant, sagging and inelastic skin. In inherited cutis laxa an abnormal synthesis of extracellular matrix proteins occurs due to genetic defects coding for diverse extracellular matrix components. Recently, different inborn errors of metabolism have been found to be associated with cutis laxa as well. In some of these metabolic conditions the pathomechanism of cutis laxa remains unknown. Cutis laxa can be inherited in an autosomal dominant, autosomal recessive and X-linked recessive inheritance pattern. Besides the skin abnormalities, in most inherited forms multiple organ systems are involved, leading to a severe, in some forms even lethal, multisystem disorder. To date no effective treatment is available for cutis laxa. This chapter focuses on inherited forms of cutis laxa, offering a practical guideline for clinicians, biochemist and geneticist to diagnose and differentiate between the different forms of cutis laxa, and providing a concise theoretical reference.

Autosomal recessive cutis laxa syndrome revisited.

The clinical spectrum of the autosomal recessive cutis laxa syndromes is highly heterogeneous with respect to organ involvement and severity. One of the major diagnostic criteria is to detect abnormal elastin fibers. In several other clinically similar autosomal recessive syndromes, however, the classic histological anomalies are absent, and the definite diagnosis remains uncertain. In cutis laxa patients mutations have been demonstrated in elastin or fibulin genes, but in the majority of patients the underlying genetic etiology remains unknown. Recently, we found mutations in the ATP6V0A2 gene in families with autosomal recessive cutis laxa. This genetic defect is associated with abnormal glycosylation leading to a distinct combined disorder of the biosynthesis of N- and O-linked glycans. Interestingly, similar mutations have been found in patients with wrinkly skin syndrome, without the presence of severe skin symptoms of elastin deficiency. These findings suggest that the cutis laxa and wrinkly skin syndromes are phenotypic variants of the same disorder. Interestingly many phenotypically similar patients carry no mutations in the ATP6V0A2 gene. The variable presence of protein glycosylation abnormalities in the diverse clinical forms of the wrinkled skin-cutis laxa syndrome spectrum necessitates revisiting the diagnostic criteria to be able to offer adequate prognosis assessment and counseling. This paper aims at describing the spectrum of clinical features of the various forms of autosomal recessive cutis laxa syndromes. Based on the recently unraveled novel genetic entity we also review the genetic aspects in cutis laxa syndromes including genotype-phenotype correlations and suggest a practical diagnostic approach.

Type II autosomal recessive cutis laxa: report of another patient and molecular studies concerning three candidate genes.

Cutis laxa is a rare disorder of connective tissue in which the skin sags excessively, giving the individual an aged appearance. In the present study we analyzed three unrelated families with type II autosomal recessive cutis laxa for mutations in three genes implicated in other forms of cutis laxa; LOX, FBLN4, and FBLN5 genes. Two individuals have been previously reported, and the third case is described in detail. No causative mutations were identified.

Cutis laxa of the autosomal recessive type in a consanguineous family.

Cutis laxa comprises a group of uncommon disorders of elastin fibers first described by Graf in the early 19th century. The main characteristic is a redundant, loose skin with deep wrinkling or sagging combined with a variable systemic involvement. Histopathologic examination presents various abnormalities of the elastin fibers. We distinguish congenital as well as acquired forms of generalized or localized cutis laxa. The mode of inheritance shows great heterogeneity: autosomal dominant, autosomal recessive and X-linked recessive inheritance have all been described. We present a severe case of autosomal recessive type 1 cutis laxa in a female patient, born in a large, consanguineous Turkish family, where three other family members had already died of the disease. A missense mutation of fibulin-5 was identified in this patient.

Elastólise cutânea generalizada adquirida pós-inflamatória: relato de cinco casos / Generalized acquired post-inflammatory cultaneous elastolysis: report of five cases

Relato de cinco casos de elastólise cutânea generalizada adquirida pós-inflamatória, observados no período de 1981 a 1993: quatro, do sexo feminino e um do masculino, sendo dois negros e três pardos. O início da doença ocorreu entre os dois e oito anos de idade. Os pacientes apresentaram quadros dermatológicos diversos na fase aguda inflamatória que precedeu à cútis laxa e ao pseudo envelhecimento cutâneo definitivo: dois, prurido agudo infantil, o terceiro, urticária, o quarto, dermatite atópica, e o quinto, queimadura térmica. Uma revisäo da literatura é feita e se estabelece uma comparaçäo desses casos com os outros 16 já descritos, discutindo-se aspecto clínicos, etiopatogênicos e terapêuticos

The differential symptomatology of errors of collagen metabolism: a tentative classification.

We address the confusion in the current classification of inherited disorders of collagen and the excessive extension of the concept of the Ehlers-Danlos "syndrome" that tends to cover many facts and conditions frequently without strong clinical connection. We propose to subdivide the collagen disorders into four main classes depending on whether skin, joints, bone, or blood vessels are mainly involved. The class with mainly skin involvement includes the different forms of cutis laxa, Ehlers-Danlos syndrome types I and II (autosomal dominant), types V and IX (X-linked recessive), type VI (autosomal recessive), and type VIII (autosomal dominant). The group with mainly articular involvement includes Larsen and related syndromes and other types with a more benign course. The conditions with mainly skeletal involvement include the different forms of osteogenesis imperfecta. The class with mainly blood vessel involvement includes disorders of type III collagen and the Marfan syndrome. This tentative classification proposes a logical clinical framework that will allow easier integration of molecular biology data.