[Cockayne syndrome: report of a case]

Cockayne Syndrome is a rare autosomal recessive disorder characterized by profound postnatal growth deficiency with loss of adipose tissue, microcephaly, mental retardation, unsteady gait and peripheral neuropathy. We are reporting a 6-year-old girl with severe growth and developmental delay, microcephaly, mental retardation, sunken eyes and photosensitive dermatitis. Her diagnosis confirmed by a defect in DNA repair in fibroblast followed exposure to ultraviolet light

[Larsen syndrome: report of a case]

Larsen syndrome is a rare disease with autosomal dominant inheritance, although both autosomal dominant and recessive inheritance has been reported. It is characterized by multiple joint dislocation, peculiar face, and vertebral anomalies. We are reporting a one-year-old boy with hips and knees dislocation, talipes equinovarus, hypertelorism, depressed nasal bridge, prominent forehead. We believe that our patient is a new case of Larsen syndrome

[Study of Prothrombin G20210A polymorphism as a genetic risk factor for cardiovascular disease in the Iranian population]

Two hundred and eight asymptomatic individuals from different origins of Iran were included in this study in order to assess the distribution of the Prothrombin G20210A polymorphism responding for cardiovascular disease [CVD] in the general Iranian population using a novel technique reverse hybridization Strip Assay for the rapid and simultaneous detection. The test is based on multiplex PCR and hybridization to a teststrip presenting a parallel array of allele-specific oligonucleotide probes for each mutation. The allele frequencies of mutant Prothrombin G20210A [0.005] in our cohort were below previously published figures on the population of Tehran [1.5]. Here we describe the distribution of mutant allele Prothrombin G20210A in different ethnicities of Iranian population and compare the results to previously reported data. Our data represent the most comprehensive study to date with respect to thrombophilic gene polymorphism in Iran

[Williams syndrome: report of a case]

Williams syndrome is one of mental retardation reasons. Most cases are sporadic but parent to child transmission has been reported. Patients have peculiar face, namely "elfin facies", with periorbital fullness, epicanthal folds, depressed nasal bridge, anteverted nares, and full lips. Cardiac malformation are supravalvular aortic stenosis, pulmonic valvular stenosis, ventricular and arterial septal defect. IQ is ranged from 40 to 80. Deletion within chromosome 7q11.23 is the reason in both sporadic and inherited cases. We are reporting a 3-year old boy, with mental retardation, periorbital fullness, full lips and cardiac malformation. In FISH studies, deletion of short arm of chromosome 7, confirmed the diagnosis of Williams syndrome

[Townes-brocks syndrome: report of a first case]

Townes-Brocks syndrome [TBS] is characterized by imperforated anus [82%], dysplastic ears [88%] [over-folded superior helices and preauricular tags] and frequently associated with sensorineural and/or conductive hearing impairment [65%], and thumb malformations [89%] [triphalangeal thumbs, duplication of the thumb, preaxial polydactyly and rarely hypoplasia of the thumb]. Renal impairment [27%], including end-stage renal disease [ESRD] [42%], may occur with or without structural abnormalities [mild malrotation, ectopia, horseshoe kidney, renal hypoplasia, polycystic kidneys, vesicoutereral reflux]. Congenital heart disease occurs in 25%, genitourinary malformations [36%]. Mental retardation occurs in approximately 10% of cases. It is autosomal dominant disease with variability in the severity of expression. We are reporting a 8-year-old girl with dysplastic ears, deafness, dysplastic thumbs, small kidneys, history of repaired imperforated anus, and rectovaginal fistula. She is also diagnosed with congenital adrenal hyperplasia. We believe our patient is the first case of Townes-Brocks syndrome with congenital adrenal hyperplasia

Deletions in the survival motor neuron gene in Iranian patients with spinal muscular atrophy

<p><b>INTRODUCTION</b>Spinal muscular atrophy (SMA) is a common neuromuscular disorder with progressive paralysis caused by the loss of alpha-motor neurons in the spinal cord. The survival motor neuron (SMN) protein is encoded by 2 genes, SMN1 and SMN2. The most frequent mutation is the biallelic deletion of exon 7 of the SMN1 gene. In SMA, SMN2 cannot compensate for the loss of SMN1, due to the exclusion of exon 7. The aim of our study was to estimate the frequency of the common SMN1 exon 7 deletion in patients referred to our centre for carrier detection and prenatal diagnosis.</p><p><b>MATERIALS AND METHODS</b>We performed the detection of exon 7 deletion of the SMN1 gene for the affected patients and fetuses suspected to have SMA.</p><p><b>RESULTS</b>Of 243 families, 195 were classified as SMA type I, 30 as type II, and 18 as type III according to their family histories. The analysis of exon 7 deletion among living affected children showed that 94% of the patients with SMA type I, 95% with type II families and 100% with type III had homozygous deletions. Of the prenatal diagnoses, 21 (22.8%) of the 92 fetuses were found to be affected and these pregnancies were terminated.</p><p><b>CONCLUSIONS</b>The homozygosity frequency for the deletion of SMN1 exon 7 for all 3 types was (94%), similar to those of Western Europe, China, Japan and Kuwait.</p>

[Coffin Lowry syndrome: a case report and review of the literatures]

Coffin Lowly Syndrome is a rare form of X-linked dominant mental retardation. Male affected patients show profound mental retardation. However, intellect ranges from normal to profoundly retarded in heterozygous females. The facial appearance is characterized by coarse face, hypertelorism, down slanting palpebral fissures, hyperplastic supraorbital ridges, broad nose with anteverted nares, prominent ears, and everted lower lips. In this article, we report a 1 5-year-old male with severe mental retardation, short stature, microcephaly, kyphoscoliosis, and characteristic feature

[Seckel syndrome report of a case and review of literature]

Seckel syndrome is a rare autosomal recessive disorder with a typical "bird-headed" appearance. It characterized by proportionate dwarfism, mental retardation, microcephaly, and growth retardation. In this article we introduce a 7-year-old girl with short stature, microcephaly and mental retardation. She had a characteristic face with receding forehead, prominent nose, micrognathia, low set ears, down slanting palpebral fissure.We believed, she suffers from Seckel Syndrome or bird-headed dwarfism syndrome

[Ellis-van creveld syndrome, with bilateral sensory-neural hearing loss: report of a case and literature review]

Ellis-van Creveld syndrome is a constellation of chondral, ectodermal and cardiac defects. It is a rare autosomal recessive syndrome with variable expression. This syndrome is also known as chondroectodermal dysplasia and mesoectodermal dysplasia. The main features are short stature, short ribs, polydactyly, dysplastic fingernails and teeth, accompanied by heart defects. We are reporting a 2-year-old girl referred to our genetics center with dwarfism, mesomelic short limbs, narrow thorax, funnel chest, short ribs, oligodontia, oral frenula, postaxial polydactyly of fingers and deafness. Her clinical findings are compatible with Ellis-van Creveld syndrome

[Asphyxiating thoracic dystrophy or Jeune syndrom report of a case and review of literature]

In this article we introduce a 3-year-old girl with marked narrowing of thoracic cage. Her parents were healthy and non-related. Her face was normal and she had normal IQ score. Her height was below 3[rd] perecentile. There was obvious lateral displacement of nipples and slightly short upper limbs. We believe, she suffer from asphyxiating thoracic cage dystrophy or Juen syndrome with autosomal recessive inheritance

[Survival motor neuron gene deletions among Iranian patients with spinal muscular atrophy]

Spinal muscular atrophy [SMA] is a common neuromuscular disorder with progressive paralysis caused by the loss of alpha-motor neuron in the spinal cord. SMN is encoded by two genes, SMN1 and SMN2, which essentially differ by a single nucleotide in exon 7. The most frequent mutation is biallelic deletion of exon 7 of the SMN1 gene. A small percentage of SMA patients present compound heterozygosity with a point mutation on one allele and deletion on the other. In the remaining cases, the disease is unlikely to be related to SMN1 defects. In spinal muscular atrophy [SMA], SMN2 is not able to compensate for the loss of SMN1 due to exclusion of exon 7. The aim of our study was to estimate the frequency of the common exon 7 SMN1 deletion in the families who referred to our center for carrier detection and prenatal diagnosis. Between March 1999 and March 2006, one hundred sixty seven families with history of at least one affected member were referred to us. We performed detection of deletion exon 7 SMN1 for the patients and carrier detection for their parents, prenatal diagnosis in subsequent pregnancies to couples who previously had an affected child became possible [63 prenatal diagnosis]. From 167 families, 139 categorized in type I of the disease, 21 in type II, and 7 in type III. Carrier detection for the parents indicated that in 96 families with history of affected member with type I SMA both parents carried the deletion in exon 7 and in 20 families, one of the parents was carrier. These rates were 16 to 1 for SMA type II, and 3 to 2 for type III SMA. Sixty-four children affected with SMA were studied, 58 of them were found to be homozygous for the loss of exon 7 of the SMN1 gene, except two patients who were heterozygote for exon 7 deletion [frequency of homozygocity: 90.7%]. Eleven of sixty-three [17.5%] fetal samples were found to be affected and these pregnancies were terminated. The molecular analysis of the biallelic exon 7 of the SMN1 deletion is a standard and reliable test in cases of SMA

Peroxisomal disorders: our experiments and physician guide

Peroxisomes are responsible for a number of very important metabolic reactions, including synthesis of glycerol ethers, shortening very long chain fatty acids [VLCFAs; C24:O and C26:O], and oxidation of the side chain of cholesterol needed for bile acid production. Peroxisomal biogenesis disorders [PBDs] are genetically and phenotypically related disorders that involve enzymatic activities of peroxisomes. They are rare mostly autosomal recessive diseases characterized by multi-systemic structural and functional abnormalities. A number of biochemical abnormalities have been described in PBD patients including decreased levels of plasmalogens, and increased levels of VLCFAs and cholestanoic acid derivatives. More than 25 different entities have been diagnosed and reported in the last two decades. The most severe condition is the Zellweger syndrome, a condition due to the absence of functional peroxisomes. Affected patients are severely ill, and show multiple congenital anomalies and neurological aberrations. Chondrodysplasia punctata is another example; they are genetically heterogeneous group of dysplasias having stippling of the epiphyses in infancy as a common feature. Peroxisomal abnormalities only found in the rhizomelic type I. There are specific biochemical tests for evaluating peroxisomal functions. The diagnoses on suspected cases can now be confirmed precisely by detailed biochemical evaluation and molecular analysis in some metabolic centers. Accumulation of certain VLCFAs [C24:0, and C26:0]; deficiency of plasmalogens, and elevation of phytanic acid are some of them. Herein we report 10 Iranian families with 15 affected cases of Zellweger syndrome and rhizomelic type I chondrodysplasia punctata [RCDP I]

Overview of lipid storage diseases and 16 years experience of biochemical analysis and prenatal diagnosis in Iran

Lipid storage diseases are a group of metabolic disorders characterized by an enzyme defect leading to progressive accumulation of heterogeneous undigested lipid substance in the lysosomal organelles, causing variety of diseases according to defective gene and accumulated lipid in the different organ1 s cells.This study was based on enzymatic assays were performed for 409 affected members of two hundred and thirty-three families whom we had screened for metabolic disorders from August 1990 to November 2006. For ruling in/out of the suspected disorder, assay of urine, blood and skin fibroblasts were performed in Erasmus University. The necessary samples were taken according to the established protocols. Among the received 409 samples, 158 samples were suspected to have some forms of lipid storage diseases, 48 did not have the suspected enzyme defect and no diagnosis was established. In 84 cases, a diagnosis was reached with the first enzyme assay. In the remaining 25 cases, the first diagnosis which was metachromatic leukodystrophy in the majority of cases was negative and the second enzyme assay for another disorder after further workup proved to be positive and diagnostic. After enzyme assay 114 individuals were shown to have some lipid storage disorder.The highest number of cases studied is the Neimann-Pick cases with 22 members from 14 families, followed by 17 members from 16 families with Metachromatic leukodystrophy, 14 cases from 11 families referred for Gaucher and 10 families with 10 affected members with Tay Sachs. In our experience, emphasis on clinical workup prior to testing can cut down unnecessary expenses, time and effort