Diagnostic dilemma's: The congenital disorders of glycosylation are clinical chameleons

Coman, David

doi:10.1038/sj.ejhg.5201962

Cited by 9 publications

(4 citation statements)

References 15 publications

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“…It is rather intriguing that many children with ARCL II present with glycosylation anomalies, and others with the same phenotype do not show any metabolic alteration, supporting genetic heterogeneity in AR cutis laxa syndrome. 53 The phenotypic variability regarding growth and development in different patients could be the consequence of consanguinity. However, these findings underline even more the usefulness of glycosylation studies in the diagnosis of ARCL II.…”

Section: Discussionmentioning

confidence: 99%

Autosomal recessive cutis laxa syndrome revisited

et al. 2009

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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.

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Section: Discussionmentioning

confidence: 99%

Autosomal recessive cutis laxa syndrome revisited

et al. 2009

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“…43,44 Ehlers-Danlos syndrome, progeroid type Ehlers-Danlos syndrome, progeroid type is a congenital disorder of glycosylation, such as type II AR cutis laxa. 45 As its name suggests, this type of EDS may be characterized by a distinctive progeroid facies as well as facial skin wrinkling, fine curly hair, scanty eyebrows and eyelashes, and downslanting palpebral fissures. Developmental delay and skeletal abnormalities are also typical.…”

Section: Ehlers-danlos Syndrome Kyphoscoliotic Type (Eds Type Vi)mentioning

confidence: 99%

Hereditary disorders of connective tissue: A guide to the emerging differential diagnosis

Murphy-Ryan

Psychogios

Lindor

2010

Genetics in Medicine

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Purpose: To create a practical desk reference for clinicians focused on the differential diagnosis of individuals presenting with features that suggest an inherited disorder of connective tissue. Methods: We searched the medical literature for distinct clinical entities that shared clinical features with Marfan syndrome and other classical inherited disorders of connective tissue. Results: Thirty-six distinct heritable disorders of connective tissue were identified that have overlapping features. These disorders were organized into two matrices according to clinical characteristics and according to causative genes. Conclusions: A broad differential diagnosis is emerging for individuals presenting with features suggestive of altered connective tissue. Recent advances in molecular genetics have aided in the delineation of these disorders. Genet Med 2010:12(6):344 -354.

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“…Consequently, there is a continuing debate [4] about another change of the CDG classification 10 years after the first change in 1999 [82]. This is reasonable, as the chronological notation of CDG does not follow a biochemical or clinical logic, and is increasingly confusing, especially concerning CDG type II, tissue-specific CDG, O-glycosylation disorders and combined N-and O-glycosylation disorders [83]. One proposal for a new classification was made recently by Jaeken et al, who discussed naming any glycosylation disorder by the term CDG and adding the name of the enzyme and/or gene [4].…”

Section: Expert Opinionmentioning

confidence: 99%