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

Rajab, Anna; Kornak, Uwe; Budde, Birgit; Hoffmann, Katrin; Jaeken, Jaak; Nürnberg, Peter; Mundlos, Stefan

doi:10.1002/ajmg.a.32143

Cited by 49 publications

(51 citation statements)

References 32 publications

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“…[107] reported on 3 children from 3 unrelated consanguineous Kuwaiti families with the same disorder. In addition, one of the families reported by Rajab et al [108] as having typical gerodermia osteodysplastica was found to have the same disorder. Two more families, one of Bahraini origin and one of Qatari origin, have been identified by Reversade et al [109] .…”

Section: Spondyloepiphyseal Dysplasia Omani Typementioning

confidence: 94%

Consanguinity and Dysmorphology in Arabs

Al‐Gazali

Hamamy²

2014

Hum Hered

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Incidence rates of congenital disorders among the 350 million inhabitants of Arab countries could be influenced via the people's demographic and cultural characteristics. Arabs usually marry at a young age and have large families. They share certain core cultural values and beliefs, with the family accepted as the central structure of society. Consanguineous marriage is favored and respected in most if not all Arab communities, and intrafamilial unions currently account for 20-50% of all marriages. First-cousin unions are especially popular and constitute almost one quarter of all marriages in many Arab countries. Consequently, autosomal recessive (AR) dysmorphic syndromes constitute a considerable proportion of all birth defects among Arabs. Arab geneticists, with their persistent commitment to advancing research, have contributed to the description of a number of rare and new AR syndromes with the identification of novel genes. The collaboration with research teams in high-income countries resulted in a plethora of data on pathogenic variants and their function in causing dysmorphic syndromes. There could still be a considerable number of rare dysmorphic syndromes that prevail among Arabs which are not hitherto described and whose underlying molecular pathologies are not yet defined. Arab countries should thus strive to deploy DNA diagnostics and to build research capability around local priorities. Furthermore, a characterization of the prevailing genetic disorders in each geographic location, together with their mutations, is needed to plan for appropriate screening and testing protocols. An overview of consanguinity in Arab countries and examples of dysmorphology syndromes associated with consanguinity with their available molecular bases will be discussed.

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Section: Spondyloepiphyseal Dysplasia Omani Typementioning

confidence: 94%

Consanguinity and Dysmorphology in Arabs

Al‐Gazali

Hamamy²

2014

Hum Hered

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“…Microcephaly and late closing fontanel are characteristic features in both entities; however, these appear in the X-linked recessive form of cutis laxa 9 23 Besides the similar cellular localization of the underlying defects there are several overlapping findings like wrinkled skin and spontaneous fractures but also a significant phenotypic difference between ARCL type II and GO patients; the presence of severe osteoporosis with early spontaneous fractures, significant dwarfism, the lack of large open fontanels and the progeroid features are distinctive for gerodermia osteodysplastica. 22 There is an evolving phenotype in both syndromes, but in GO the dysmorphic features might get more prominent through the disease course in contrast to the improving phenotype in other forms of ARCL type II. Wrinkled skin has been described in patients diagnosed with William's Syndrome, and elastin mutations have been described in children with cutis laxa syndrome, without the classical features of William's Syndrome (MIM 194050).…”

Section: -11mentioning

confidence: 99%

“…The frequency of gerodermia osteodysplastica and XRCL appears to be comparable with the frequency of ADCL based on the number of reports. 10,18,22,23 It is difficult to assess the frequency of XLCL due to the phenotypic overlap with Menkes Syndrome. 9 In addition to these numbers several patients have been reported with a syndromic appearance associated with cutis laxa.…”

Section: Population Datamentioning

confidence: 99%

“…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. The histology therefore is an important, but not indispensable tool in the diagnostics.…”

Section: Histology In Autosomal Recessive Cutis Laxa Syndromesmentioning

confidence: 99%

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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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“…However, they noted that microcephaly and the late closing of the large fontanel were rare in patients with GO but were often seen in patients with ARCL2B. We agree that microcephaly is rare in GO [Hunter et al, 1978;Rajab et al, 2008]. On the other hand, the late closing of the large fontanel is not a rare sign in patients with GO and SCYL1BP1 mutations [Hunter et al, 1978;Morava et al, 2009].…”

mentioning

confidence: 90%