Figure 1 - uploaded by Kamel Ajlouni
Content may be subject to copyright.
Source publication
Prior to excision methylene blue dye was injected into the cyst revealing a large stained area. This was then dissected revealing a fine tract that passed into fascia at the level of the head of the fibula. This tract was ligated and cut. Histology revealed what looked like a thick walled cyst with flattened cells lining it. These lining cells are...
Contexts in source publication
Context 1
... report a 2-year-old girl with wrinkly skin syndrome (WSS). At birth, she was noted to have a large head with a large anterior fontanelle and facial dysmorphism with no raised intracranial pressure ( Fig. 1e). At the age of 1 year, she manifested developmental delay with a length of 68 cm (2nd centile), weight 6 kg (< 0.4th centile) and head circumference of 48 cm. By the age of 2 years, she manifested the typical features of the syndrome which included skin wrinkling on the dorsa of the hands, feet and anterior abdominal wall, prominent ...
Context 2
... age of 1 year, she manifested developmental delay with a length of 68 cm (2nd centile), weight 6 kg (< 0.4th centile) and head circumference of 48 cm. By the age of 2 years, she manifested the typical features of the syndrome which included skin wrinkling on the dorsa of the hands, feet and anterior abdominal wall, prominent veins on the chest (Fig. 1a-c), and hyperextensibility of small joints of the hands and feet. She had a triangular senile-looking face with hypotelorism, a prominent bulbous nose, large protruding ears and brachycephaly ( Fig. 1d) three affected siblings born to consanguineous Iraqi-Jewish parents. In the last 30 years, 14 additional cases were reported, mostly from ...
Context 3
... features of the syndrome which included skin wrinkling on the dorsa of the hands, feet and anterior abdominal wall, prominent veins on the chest (Fig. 1a-c), and hyperextensibility of small joints of the hands and feet. She had a triangular senile-looking face with hypotelorism, a prominent bulbous nose, large protruding ears and brachycephaly ( Fig. 1d) three affected siblings born to consanguineous Iraqi-Jewish parents. In the last 30 years, 14 additional cases were reported, mostly from the Middle East. 2-4 A chromosomal anomaly was detected in only one family where the affected mother and her two affected children showed a del(2q). 3 The clinical features of two other syndromes, ...
Citations
... ARCL type II has features overlapping with wrinkly skin syndrome; as a result, they are regarded as one disorder with a variable spectrum of severity by some authors. [4] Because of the many phenotypic similarities in Geroderma osteodysplastica and wrinkly skin syndrome, it has been proposed that these two conditions represent the same disorder. [5] Morava et al. reported phenotypic features of 10 children with ARCL II who had associated glycosylation defects. ...
Autosomal recessive cutis laxa type-II (ARCLII) is a spectrum of clinical disorders with prenatal and postnatal growth retardation, cutis laxa, dysmorphism, and skeletal abnormalities. We report the case of a 14-month-old boy with developmental delay, hypotonia, dysmorphism, and loose skin. A novel homozygous variant was observed in ATP6VOA2 gene. Clinical spectrum of ARCLII is highly heterogeneous and molecular analysis should be done to confirm the diagnosis.
... ARCL2B is characterized by intra-uterine growth retardation, cutis laxa, wrinkling of skin, particularly of dorsum of hands and feet, visible veins on the chest, congenital hip dislocation, hyperextensible joints, and adducted thumbs. Phenotypic facial features include a broad and prominent forehead, aged appearance, triangular face, and thin nose[11][12][13][14]. Neurological findings observed in this condition are hypotonia, developmental delay, intellectual disability, and dysgenesis or agenesis of the corpus callosum[11]. ...
Cutis laxa is a heterogeneous condition characterized by redundant, sagging, inelastic, and wrinkled skin. The inherited forms of this disease are rare and can have autosomal dominant, autosomal recessive, or X-linked inheritance. Three of the autosomal recessive cutis laxa syndromes, namely cutis laxa IIA (ARCL2A), cutis laxa IIB (ARCL2B), and geroderma osteodysplastica (GO), have very similar clinical features, complicating accurate diagnosis. Individuals with these conditions often present with cutis laxa, progeroid features, and hyperextensible joints. These conditions also share additional features, such as short stature, hypotonia, and congenital hip dislocation, but the severity and frequency of these findings are variable in each of these cutis laxa syndromes. The characteristic features for ARCL2A are abnormal isoelectric focusing and facial features, including downslanting palpebral fissures and a long philtrum. Rather, the clinical phenotype of ARCL2B includes severe wrinkling of the dorsum of the hands and feet, wormian bones, athetoid movements, lipodystrophy, cataract and corneal clouding, a thin triangular face, and a pinched nose. Normal cognition and osteopenia leading to pathological fractures, maxillary hypoplasia, and oblique furrowing from the outer canthus to the lateral border of the supraorbital ridge are discriminative features for GO. Here we present 10 Iranian patients who were initially diagnosed clinically using the respective features of each cutis laxa syndrome. Each patient’s clinical diagnosis was then confirmed with molecular investigation of the responsible gene. Review of the clinical features from the cases reported from the literature also supports our conclusions.
... Therefore, we compared the clinical findings of the patients reported here with those described by Newman et al. [2008], nine patients with GORAB gene mutation had been identified by Hennies et al. [2008]; four of those patients (Family B) had been reported by Rajab et al. [2008], four of Family V have been reported by Hunter et al. [1978], one in Picco et al. [1993] and by Al-Dosari and Alkuraya [2009]. The comparison also included the patients with PYCR1 mutation, reported by Guernsey et al. [2009] and Reversade et al. [2009]; three of those patients (Family A) had been reported by Rajab et al. [2008], three in Kunze et al. [1985], four in Al-Gazali et al. [2001], three in Nanda et al. [2008], one in Hamamy et al. [2005], one in Sommer [2007], one in Guerra et al. [2004] in Table I. Overall, the clinical similarities of disorders caused by mutations in GORAB and PYCR1 are striking. ...
Geroderma osteodysplasticum is a rare autosomal recessive disorder characterized by wrinkled skin on the dorsum of the hands and feet, osteopenia, prognathism, and an elongated and lax face. The mutated gene was identified as GORAB (SCYL1BP1). As well, the PYCR1 gene also was shown to be mutated in a similar disease, designated cutis laxa, autosomal recessive, type IIB (ARCL2B) or cutis laxa with progeroid features. We describe here the clinical findings in four affected individuals in a family with geroderma osteodysplasticum with mental retardation and a homozygous mutation in PYCR1. Although the disease resulting from recessive mutations in that gene has been recently designated ARCL2B, some clinical features, such as prognathism, elongated and lax face, osteopenia and limitation of skin wrinkling to the dorsum of hands and feet, in the patients reported here as well as in others reported with PYCR1 mutations, are generally more common in geroderma osteodysplasticum resulting from recessive GORAB mutations. While the patients with GORAB mutations have severe osteopenia, the patients with PYCR1 mutations have severe mental retardation. In conclusion, the phenotype caused by PYCR1 mutations corresponds to geroderma osteodysplasticum rather than ARCL2B.
... In many subjects, agenesis of the corpus callosum was evident. Although most affected individuals were classified as having gerodermia osteodysplastica or WSS, more severely affected individuals also showed childhood cataracts or dystonic movements and were therefore diagnosed as having DBS 1,3,[5][6][7][8][9] . ...
... Furthermore, fibroblasts from the subjects described here did not show the proliferation defect described upon P5CS deficiency 16 . The phenotype of PYCR1-related disease overlaps with other forms of cutis laxa, mirrored by the fact that affected individuals from this cohort have been previously described under the diagnoses WSS, gerodermia osteodysplastica or DBS 1,3,[5][6][7][8][9] . Whereas gerodermia osteodysplastica caused by mutations in GORAB (formerly known as SCYL1BP1) does not lead to intellectual impairment, ARCL2 often includes mild or moderate mental retardation and brain anomalies 2,17,18 . ...
Autosomal recessive cutis laxa (ARCL) describes a group of syndromal disorders that are often associated with a progeroid appearance, lax and wrinkled skin, osteopenia and mental retardation. Homozygosity mapping in several kindreds with ARCL identified a candidate region on chromosome 17q25. By high-throughput sequencing of the entire candidate region, we detected disease-causing mutations in the gene PYCR1. We found that the gene product, an enzyme involved in proline metabolism, localizes to mitochondria. Altered mitochondrial morphology, membrane potential and increased apoptosis rate upon oxidative stress were evident in fibroblasts from affected individuals. Knockdown of the orthologous genes in Xenopus and zebrafish led to epidermal hypoplasia and blistering that was accompanied by a massive increase of apoptosis. Our findings link mutations in PYCR1 to altered mitochondrial function and progeroid changes in connective tissues.
... Wrinkly skin syndrome (WSS; OMIM 278250) is another rare autosomal recessive condition that is characterized by congenital wrinkly skin, prominent venous texture, intrauterine growth retardation, developmental delay, an aged appearance, and various craniofacial and musculoskeletal abnormalities. Since first being described in 1973, around 22 patients have subsequently been reported in the literature (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). The occurrences of GO and WSS have been described in different races, but most of the reports are from the countries of the Middle East (8,10,11,14,16,23) and this is linked to the high incidence of consanguineous marriages in this region. ...
... Wrinkly skin syndrome (WSS; OMIM 278250) is another rare autosomal recessive condition that is characterized by congenital wrinkly skin, prominent venous texture, intrauterine growth retardation, developmental delay, an aged appearance, and various craniofacial and musculoskeletal abnormalities. Since first being described in 1973, around 22 patients have subsequently been reported in the literature (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). The occurrences of GO and WSS have been described in different races, but most of the reports are from the countries of the Middle East (8,10,11,14,16,23) and this is linked to the high incidence of consanguineous marriages in this region. ...
... Gazit et al (14) coined the term WSS to describe congenital wrinkly skin, more prominent on the dorsae of the hands, the feet, and abdomen, prenatal and postnatal growth retardation hypermobility of joints, increased numbers of creases on palms and soles, and a prominent venous pattern. Subsequently, many patients with additional features were described (13)(14)(15)(16)(17)(18)(19)(20)(21)(22). Al-Gazali et al (11) reported five patients who had overlapping features of GO and WSS. ...
Gerodermia osteodysplastica and wrinkly skin syndrome are rare autosomal recessive disorders. Due to the many phenotypic similarities in these two conditions, it has been proposed that they represent the same disorder. Both conditions are well delineated in the genetic literature, but despite skin involvement being a striking feature, they are rarely reported in dermatology journals. In this report, we describe three Arab children from two consanguineous families who exhibit overlapping features of gerodermia osteodysplastica and wrinkly skin syndrome. All the patients had dysmorphic facial features, wrinkled skin more marked on the hands and feet, hyperextensible joints, intrauterine growth retardation, developmental delay, congenital dislocation of hips, and osteoporosis. Our observations also support the contention that gerodermia osteodysplastica and wrinkly skin syndrome have the same clinical spectrum; however, this needs to be confirmed at the molecular level.
... The high consanguinity rate and the large family size in Jordan have contributed to the description of a number of rare [29] and new autosomal recessive conditions with mapping of novel loci ( table 4 ). ...
The population in Jordan mounted from half a million in 1952 to 5.3 millions in 2004 and is composed of a variety of ethnic groups, the majority being Arabs. Couples nowadays tend to have fewer children, with the total fertility rate falling from 7.4 in 1976 to 3.7 in 2004. Consanguineous marriages are traditionally favored, with the preferred marriage partner being the offspring of the father's brother. First-cousin marriages declined from 28.5% for marriages contracted between 1950 and 1979 to 19.5% for marriages contracted after 1980. In the overall population, carrier rates for beta-thalassemia, alpha-thalassemia and sickle cell anemia are in the range of 2-4%, 3.2-12% of males have glucose-6-phosphate dehydrogenase deficiency, and the prevalences for familial Mediterranean fever and cystic fibrosis were estimated at around 0.04% each. A mandatory premarital screening program for beta-thalassemia carriers commenced in June 2004. The high consanguinity rate and the large family size in Jordan have contributed to the description of a number of rare and new autosomal recessive conditions. Genetic services in Jordan are still scarce and do not cover all the country due to the major impediments of a paucity of resources and trained health professionals in the area of medical genetics. The demographic data suggest that the health system in Jordan is capable of introducing some basic community genetic services into the primary health care program through comprehensive and cost-effective programs.
The study of high axial myopia in the setting of antecedent, concurrent or subsequent ocular disorders, systemic diseases, hereditary syndromes, and systemic drug use may contribute to our understanding of the pathogenesis of myopia and even set the occasion for the development of treatment. Although early recognition of mild myopic changes that commonly arise with certain ocular and systemic factors may limit the burden of vision loss with simple refractive correction, the recognition of high and pathologic axial myopia is important since there is a risk of permanent vision loss from vision-threatening sequelae. Therefore, the study of cases of high axial myopia, and specifically those cases in which there may be a causal relationship, is of particular interest. Additionally, recognition of the tendency of some syndromes to be associated with high myopia heightens the clinical suspicion for detection of severe refractive errors in patients who maybe preverbal or unable to effectively communicate. Clinical studies and basic scientific discoveries oftentimes mirror and motivate each other. In this chapter, we detail clinical observations and studies that have been proven, or may in the future prove themselves, relevant to current thoughts on emmetropization and animal models of myopia discussed more thoroughly elsewhere in this book.
The study of high axial myopia in the setting of antecedent, concurrent, or subsequent ocular disorders, systemic diseases, hereditary syndromes, and systemic drug use may contribute to our understanding of the pathogenesis of myopia and even set the occasion for the development of treatment. Although early recognition of mild myopic changes that commonly arise with certain ocular and systemic factors may limit the burden of vision loss with simple refractive correction, the recognition of high and pathologic axial myopia is important since there is a risk of permanent vision loss from vision-threatening sequelae. Therefore, the study of cases of high axial myopia, and specifically those cases in which there may be a causal relationship, is of particular interest. Additionally, recognition of the tendency of some syndromes to be associated with high myopia heightens the clinical suspicion for detection of severe refractive errors in patients who may be preverbal or unable to effectively communicate. Clinical studies and basic scientific discoveries oftentimes mirror and motivate each other. In this chapter, we detail clinical observations and studies that have proven or may in the future prove themselves relevant to current thoughts on emmetropization and animal models of myopia discussed more thoroughly elsewhere in this book.
