Dwarfism, Oligophrenia, and Elastictissue Hypoplasia: A New Syndrome?

Barsy, A.M. De; Moens, Ellen; Dierckx, L

doi:10.1016/s0140-6736(67)90093-1

Cited by 24 publications

(32 citation statements)

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“…We could exclude Ehlers-Danlos syndrome as there was no evidence of easy skin bruising and abnormal healing. We did not observe dwarfism, oligophrenia or corneal degeneration as described for De Barsy syndrome (OMIM 219150) [de Barsy et al, 1968]. Although both, GO and WSS, are characterized by excessive wrinkling of the skin, the degree and the extent of the wrinkling is different, as previously pointed out by Hunter et al, [1978] and Casamassima et al, [1987].…”

Section: Discussionsupporting

confidence: 72%

Geroderma osteodysplasticum hereditaria and wrinkly skin syndrome in 22 patients from Oman

Rajab

Kornak

Budde

et al. 2008

American J of Med Genetics Pt A

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Excessive skin wrinkling and cutis laxa are seen in many genetic conditions and overlapping features can make a clinical diagnosis difficult. Here we report on 22 Omani patients from 11 consanguineous families with the diagnosis of wrinkly skin syndrome (WSS, OMIM 278250) or geroderma osteodysplasticum hereditaria (GO, OMIM 231070). The WSS phenotype evolves during early childhood and includes a generalized and excessive skin wrinkling, dental problems, herniae, foot deformities, hip dislocations, growth retardation, and a large anterior fontanelle. The facial gestalt is characterized by a broad nasal bridge, hypertelorism, and downslanting palpebral fissures. We were unable to differentiate between WSS and cutis laxa with growth and developmental delay (CLGDD, OMIM 219200) suggesting that both can be considered as one entity. Distinct hallmarks of GO were skin wrinkling limited to the dorsum of hands and feet and to the abdomen, normal fontanelles, maxillary hypoplasia, bowed long bones, and osteopenia with frequent fractures. In contrast to the attenuation of the skin phenotype with age in WSS, adult patients with GO appeared prematurely aged. A serum sialotransferrin type 2 pattern was found in all four WSS patients tested. Apolipoprotein CIII (a marker for O-glycosylation) was normal suggesting that WSS is frequently associated with a N-protein glycosylation defect, probably at the level of processing (CDG-II). All four investigated GO patients showed normal sialotransferrin patterns. The known loci for cutis laxa and WSS on 2q31, 5q23-q31, 7q11, 11q13, and 14q32 were excluded. We suggest that WSS and GO are distinct entities with overlapping features.

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Section: Discussionsupporting

confidence: 72%

Geroderma osteodysplasticum hereditaria and wrinkly skin syndrome in 22 patients from Oman

Rajab

Kornak

Budde

et al. 2008

American J of Med Genetics Pt A

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“…Several patients with the classic clinical phenotype of De Barsy Syndrome have been reported with normal skin biopsy, but in others reduced density of elastic fibers or abnormal elastin fiber synthesis were observed. 2,20,38 The presence or absence of generalized elastin fiber anomalies by histology are not part of the diagnostic criteria in patients with gerodermia osteodysplastica. 22 Even more surprising in autosomal dominant forms, in the presence of an ELN mutation, some individuals could present with mild abnormalities, such as decreased amount of elastic fibers seen by electron microscopy or without histologic alterations.…”

Section: Histology In Autosomal Recessive Cutis Laxa Syndromesmentioning

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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“…These patients show thin and translucent skin, visibility of the veins and a specific facial gestalt with triangular face and prognathism resulting in a progeroid appearance. Additionally, affected individuals show skeletal and ophthalmological abnormalities, intrauterine growth retardation and in the majority of cases considerable intellectual disability [9,10]. ARCL patients with de Barsy-like symptoms may harbor mutations in either PYCR1 (pyrollin-5-carboxylate reductase 1) (ARCLIIB; OMIM 612940) or ALDH18A1 (P5CS) (pyrrolin-5-carboxylate synthase 1) (ARCLIIIA; OMIM 219150).…”

Section: Introductionmentioning

confidence: 99%

Severe congenital cutis laxa with cardiovascular manifestations due to homozygous deletions in ALDH18A1

Fischer

Callewaert

Schröter

et al. 2014

Molecular Genetics and Metabolism

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Autosomal recessive cutis laxa (ARCL) type 2 constitutes a heterogeneous group of diseases mainly characterized by lax and wrinkled skin, skeletal anomalies, and a variable degree of intellectual disability. ALDH18A1-related ARCL is the most severe form within this disease spectrum. Here we report on the clinical and molecular findings of two affected individuals from two unrelated families. The patients presented with typical features of de Barsy syndrome and an overall progeroid appearance. However, the phenotype was highly variable including cardiovascular involvement in the more severe case. Investigation of a skin biopsy of one patient revealed not only the typical alterations of elastic fibers, but also an altered structure of mitochondria in cutaneous fibroblasts. Using conventional sequencing and copy number analysis we identified a frameshift deletion of one nucleotide and a microdeletion affecting the ALDH18A1 gene, respectively, in a homozygous state in both patients. Expression analysis in dermal fibroblasts from the patient carrying the microdeletion showed an almost complete absence of the ALDH18A1 mRNA resulting in an absence of the ALDH18A1 protein. So far, only 13 affected individuals from seven unrelated families suffering from ALDH18A1-related cutis laxa have been described in literature. Our findings provide new insights into the clinical spectrum and show that beside point mutations microdeletions are a possible cause of ALDH18A1-ARCL.

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Dwarfism, Oligophrenia, and Elastictissue Hypoplasia: A New Syndrome?

Cited by 24 publications

References 1 publication

Geroderma osteodysplasticum hereditaria and wrinkly skin syndrome in 22 patients from Oman

Geroderma osteodysplasticum hereditaria and wrinkly skin syndrome in 22 patients from Oman

Autosomal recessive cutis laxa syndrome revisited

Severe congenital cutis laxa with cardiovascular manifestations due to homozygous deletions in ALDH18A1

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