1/8. genotype/phenotype correlations of males affected by Simpson-Golabi-Behmel syndrome with GPC3 gene mutations: patient report and review of the literature.Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth syndrome with associated visceral and skeletal anomalies. Deletions or point mutations involving the glypican-3 (GPC3) gene at Xq26 are associated with a relatively milder form of this disorder (SGBS1). GPC3 encodes a putative extracellular proteoglycan, glypican-3, that is inferred to play an important role in growth control in embryonic mesodermal tissues in which it is selectively expressed. It appears to form a complex with insulin-like growth factor-II (IGF-II), and might thereby modulate IGF-II action. We reviewed the clinical findings of all published patients with SGBS1 with GPC3 mutations to confirm the clinical specificity for the SGBS1 phenotype. Moreover, we report on a new patient with a GPC3 deletion and IGF-II evaluation.- - - - - - - - - - ranking = 1keywords = complex (Clic here for more details about this article) |
2/8. Postmortem findings in the coffin-lowry syndrome.The coffin-lowry syndrome (CLS) is a congenital disorder that can be recognized by retarded growth and development, the characteristic appearance of the face and hands, and often by the typical deformities of the back and chest; there are many other anomalies. The history of the syndrome is reviewed, noting the x-linked semidominant pattern of inheritance, and two autopsies are presented and compared with the three autopsy reports that have been published previously. The five young patients died at ages between 18 to 28 years of advancing pneumonia, aspiration of food into the trachea, or postoperative complications. There were lesions or abnormalities in the heart, brain, lungs, liver, skeleton, kidneys, intestines, and other organs. Molecular geneticists have located the CLS gene or Rsk-2 gene at Xp22.2 and demonstrated that it works by influencing the activation of other genes. The "monopolygenic" pattern may help to explain the large number of seemingly unrelated abnormalities that make up this syndrome.- - - - - - - - - - ranking = 104953.98357979keywords = x-linked (Clic here for more details about this article) |
3/8. X-linked lissencephaly with abnormal genitalia associated with renal phosphate wasting.X-linked lissencephaly with abnormal genitalia (XLAG) is a rare disorder caused by mutations in the aristaless-related homeobox (ARX) gene. We report on the clinical data of a boy with a 1-bp deletion (790 delC) resulting in a frame shift in the ARX gene and prolonged survival until age 18 months. Similar to other patients, the boy showed postnatal microcephaly, hypothalamic dysfunction, intractable neonatal seizures, and chronic diarrhoea. In addition, he suffered from exocrine pancreatic insufficiency and renal phosphate wasting became apparent from age 5 months, both of which have not been described previously in XLAG. This allows us to speculate that the phenotype of XLAG is more complex than hitherto known and may include renal phosphate wasting which might not have been observed in other patients due to early death.- - - - - - - - - - ranking = 1keywords = complex (Clic here for more details about this article) |
4/8. Cerebral, cerebellar, and colobomatous anomalies in three related males: sex-linked inheritance in a newly recognized syndrome with features overlapping with Joubert syndrome.We present a so far unrecognized X-linked mental retardation syndrome with features overlapping with Joubert syndrome (JBS). Two brothers showed hypotonia, mental retardation, ocular abnormalities with impaired vision and colobomas and a breathing pattern compatible with JBS. neuroimaging revealed cerebellar vermis hypoplasia and ventriculomegaly. A tentative diagnosis of JBS was made, and autosomal recessive inheritance considered most likely. In a subsequent pregnancy that occurred after artificial donor insemination, ultrasound in the 22nd week revealed a Dandy-Walker malformation and hydrocephaly. At autopsy at 34 weeks of gestation, the male infant showed cerebellar vermis aplasia and abnormalities of the brainstem and cerebral cortex. He was considered to have the same disorder as his two half-brothers. This renders the pedigree highly suggestive of X-linked inheritance. The clinical symptoms of this syndrome resemble JBS. However, the absence of the molar tooth sign and the X-linked inheritance do not support JBS. We propose the name X-linked cerebral-cerebellar-coloboma syndrome to distinguish the two disorders. Differentiation of the two disorders is especially important in genetic counseling, where artificial donor insemination may be considered as a means of reducing the recurrence risk, or when female relatives of the patient are concerned.- - - - - - - - - - ranking = 419815.93431918keywords = x-linked (Clic here for more details about this article) |
5/8. incontinentia pigmenti (IP2): familiar case report with affected men. literature review.incontinentia pigmenti is a genodermatosis described by Garrod and in 1920 by Bloch, Sulzberger, Siemens y Bardach. It is an ectodermic disorder that affects skin, teeth, eyes and may also have neurological problems. The IP2 name describes the histological characteristics, the incontinence of melanin into the melanocytes cells in the epidermal basal layer and its presence in superficial dermis. IP2 is an x-linked dominant condition but genetic heterogeneity may exist. CASE REPORT: The patient was 4 yrs 5 months old when she came for the first time. In a physical exploration she presented sparse and thin hair, eyelashes and eyebrows, beaked nose, labial protrusion, the four central teeth have a conic crown and there was also a delayed eruption of other teeth, right eye strabismus, hipoacusia, language defects and a trunk, legs, feet, and face dermatosis characterized by grouped vesicles, hyperkeratotic and warty lesions and brownish-gray lesions in a lineal pattern. The patient s father had hypopigmented lesions in the posterior regions of both legs. The oral clinical and radiographic exams showed diverse anomalies. Both the patient's and the father's chromosomal studies were normal. DISCUSSION: In the present case we can see that the father has IP2 without supernumeraries X, with the antecedent that his mother had something similar. It is possible that the inheritance was autosomic dominant or it is a different mutation of NEMO (NF-kappa-B essential modulator) gene to a classical one, which was found in some affected men. It is necessary to carry out a molecular study of these patients.- - - - - - - - - - ranking = 104953.98357979keywords = x-linked (Clic here for more details about this article) |
6/8. Autoimmune retinopathy with RPE hypersensitivity and 'negative ERG' in X-linked hyper-IgM syndrome.PURPOSE: To report the clinical, electrophysiological, and immunological features of a patient with X-linked hyper-igm immunodeficiency syndrome type 1 (HIGM1) accompanied by a novel type of autoimmune retinopathy, including retinal pigment epithelium (RPE) hypersensitivity. methods: Comprehensive ophthalmological examinations, electrophysiological function testing, and inquiries into the immunological status of a 13-year-old presenting with subacute loss of vision in association with a molecularly confirmed diagnosis of HIGM1 were performed. The patient was genotyped by a PCR-based sequence tag content mapping strategy to define the genetic defect within the causative X-HIM gene TNFSF5. Since conventional allogenic bone marrow transplantation has been reported to cure HIGM1, a peripheral blood stem-cell transplantation was performed. RESULTS: (1) The patient's reduced visual acuity included prolonged dark adaptation and visual field constriction. electrophysiology revealed a 'negative ERG' indicating post-receptoral dysfunction. (2) Initial immunological examination of the patient's serum identified abnormal antibody activity with components of the photoreceptors and the inner nuclear layer. The patient later developed indications of RPE hypersensitivity. A massively reduced light-peak to dark-trough ratio of the EOG slow oscillations (L/D ratio) corresponded to impaired RPE-photoreceptor complex function. (3) Molecular genetic analyses revealed the patient to be nullizygous for the tumor necrosis factor ligand member 5 gene (TNFSF5; CD40LG). A large chromosomal deletion of approximately 27.6-32.3 kb in size was identified in Xq26. (4) The transplant with its associated immunomodulation appeared to worsen rather than improve the patient's condition. CONCLUSIONS: The fundus appearance and electrophysiological function testing revealed indications of atypical retinal degeneration. However, the clinical course and the serological findings were consistent with those of ocular autoimmunity involving both antiretinal activity and RPE hypersensitivity. In this case, peripheral stem-cell transfusion with its associated chemotherapy failed to benefit the patient's vision; indications of autoimmunity appeared to increase following this treatment.- - - - - - - - - - ranking = 1keywords = complex (Clic here for more details about this article) |
7/8. Mechanistic associations of a mild phenotype of immunodysregulation, polyendocrinopathy, enteropathy, x-linked syndrome.BACKGROUND & AIMS: The syndrome of immunodysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) is a rare disorder resulting in the expression of multiple autoimmune and allergic features. Early onset enteropathy and type 1 diabetes (T1D) are the most common clinical features. The IPEX syndrome is caused by mutations of the FOXP3 gene, which is essential for the development of regulatory T cells (Treg). We describe 2 unrelated patients with IPEX syndrome with a mild clinical phenotype and with novel FOXP3 mutations and the phenotypic and functional characterization of their Treg cells. methods: The FOXP3 gene was analyzed by sequencing amplimers from genomic dna. Treg cells were characterized by evaluating the number of CD4 CD25 T cells and their functional ability to suppress the proliferation of autologous CD4 CD25- effector T cells stimulated with anti-CD3 and anti-CD28 antibodies. RESULTS: A 7-year-old boy and a 24-year-old man presented with autoimmune enteropathy characterized by early onset persistent diarrhea not associated with T1D or other endocrinopathies. These 2 patients carry novel FOXP3 mutations that do not abrogate the function of the forkhead domain. They have normal numbers of CD4 CD25 T lymphocytes, however, these show severely defective suppressive function in vitro. CONCLUSIONS: Our 2 patients show that IPEX patients may present with early onset enteropathy and long-term survival without T1D or other endocrinopathies. This milder phenotype may be associated with FOXP3 mutations that do not abrogate the function of the forkhead domain.- - - - - - - - - - ranking = 419815.93431918keywords = x-linked (Clic here for more details about this article) |
8/8. blepharophimosis-mental retardation (BMR) syndromes: A proposed clinical classification of the so-called Ohdo syndrome, and delineation of two new BMR syndromes, one X-linked and one autosomal recessive.We report on 11 patients from 8 families with a blepharophimosis and mental retardation syndrome (BMRS) phenotype. Using current nosology, five sporadic patients have Ohdo syndrome, associated with congenital hypothyroidism in two of them (thus also compatible with a diagnosis of Young-Simpson syndrome). In two affected sibs with milder phenotype, compensated hypothyroidism was demonstrated. In another family, an affected boy was born to the unaffected sister of a previously reported patient. Finally, in the last sibship, two affected boys in addition had severe microcephaly and neurological anomalies. A definitive clinical and etiologic classification of BMRS is lacking, but closer phenotypic analysis should lead to a more useful appraisal of the BMRS phenotype. We suggest discontinuing the systematic use of the term "Ohdo syndrome" when referring to patients with BMRS. We propose a classification of BMRS into five groups: (1) del(3p) syndrome, (possibly overlooked in older reports); (2) BMRS, Ohdo type, limited to the original patients of Ohdo; (3) BMRS SBBYS (Say-Barber/Biesecker/Young-Simpson) type, with distinctive dysmorphic features and inconstant anomalies including heart defect, optic atrophy, deafness, hypoplastic teeth, cleft palate, joint limitations, and hypothyroidism. BMRS type SBBYS is probably an etiologically heterogeneous phenotype, as AD and apparently AR forms exist; (4) BMRS, MKB (Maat-Kievit-Brunner) type, with coarse, triangular face, which is probably sex-linked; (5) BMRS V (Verloes) type, a probable new type with severe microcephaly, hypsarrhythmia, adducted thumbs, cleft palate, and abnormal genitalia, which is likely autosomal recessive. Types MKB and V are newly described here.- - - - - - - - - - ranking = 104953.98357979keywords = x-linked (Clic here for more details about this article) |