Ehlers-Danlos syndrome type VI in a 17-year-old Iranian boy with severe muscular weakness - a diagnostic challenge?

The Ehlers-Danlos syndrome type VI [EDSVI] is an autosomal recessive connective tissue disease which is characterized by severe hypotonia at birth, progressive kyphoscoliosis, skin hyperelasticity and fragility, joint hypermobility and [sub-]luxations, microcornea, rupture of arteries and the eye globe, and osteopenia. The enzyme collagen lysyl hydroxylase [LH1] is deficient in these patients due to mutations in the PLOD1 gene. We report a 17-year-old boy, born to related parents, with severe kyphoscoliosis, scar formation, joint hypermobility and multiple dislocations, muscular weakness, rupture of an ocular globe, and a history of severe infantile hypotonia. EDS VI was suspected clinically and confirmed by an elevated ratio of urinary total lysyl pyridinoline to hydroxylysyl pyridinoline, abnormal electrophoretic mobility of the alpha-collagen chains, and mutation analysis. Because of the high rate of consanguineous marriages in Iran and, as a consequence thereof, an increased rate of autosomal recessive disorders, we urge physicians to consider EDS VI in the differential diagnosis of severe infantile hypotonia and muscular weakness, a disorder which can easily be confirmed by the analysis of urinary pyridinolines that is highly specific, sensitive, robust, fast, non-invasive, and inexpensive

[Study of factor V Leiden 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 Factor V Leiden 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. The prevalences of mutant Factor V Leiden [1.2%] in our cohort was below previously published figures on the population of Tehran [2.7%]. Here we describe the distribution of mutant allele FV Leiden 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

[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 ACE Ins/Del 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 ACE Ins/Del 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 test strip presenting a parallel array of allele-specific oligonucleotide probes. The allele frequencies of mutant ACE D/I polymorphism [0.62] was remarkably high. Mutant ACE D/I polymorphism in Iran occurred as high as East Mediterranean populations, and exceeded the lower frequencies known from Europe, India and most of Asia. Here we describe the distribution of mutant allele ACE D/I polymorphism in different ethnicities of Iranian population. Our data represent the only comprehensive study to date with respect to ACE D/I gene polymorphism in Iran

[Study of MTHFR A1298C 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 MTHFR A1298C 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 prevalence of mutant MTHFR A1298C in our study population [0.42], was remarkably high. Mutant MTHFR A1298C in Iran occurred less frequently than among Europeans, but exceeded the much lower frequencies known from India and most of Asia. Here we describe the distribution of mutant allele MTHFR A1298C in different ethnicities of Iranian population and compare the results to previously reported data. Our data represent the only comprehensive study to date with respect to thrombophilic gene polymorphism in Iran

[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

[Study of PAI-1 4G/5G 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 PAI-1 4G/5G 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 test strip presenting a parallel array of allele-specific oligonucleotide probes. The allele frequency of mutant PAI-1 4G/5G [0.45] is comparable to that of Europeans, but exceeded the much lower frequencies known from the most of Asia. Here we describe the distribution of mutant allele PAI-1 4G/5G in different ethnicities of Iranian population. Our data represent the only 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

Distal renal tubular acidosis and its relationship with hearing loss in children: preliminary report

In autosomal recessive distal renal tubular acidosis [DRTA], a substantial fraction of the patients have progressive bilateral sensorineural hearing loss. This coexistence is due to the mutations of a gene expressed both in the kidney and in the cochlea. The aim of this study was to assess the correlation between hearing loss and DRTA. In this study, 51 children diagnosed with renal tubular acidosis were evaluated. Diagnosis of DRTA was based on clinical manifestations and detection of normal anion gap metabolic acidosis, urine pH higher than 5.5, and positive urinary anion gap. Audiometry was performed in children with DRTA and sequencing of the ATP6V1B1 gene was done for those with sensorineural hearing loss. Twenty-seven patients [52.9%] had DRTA, of whom 51.9% were younger than 1 year old, 55.6% were boys, and 44.4% were girls. Eleven patients [40.7%] had bilateral sensorineural hearing loss, consisting of 5 of 15 boys [33.3%] and 6 of 12 girls [50.0%]. There was no correlation between hearing loss and gender. Three patients with hearing loss had mutation in the ATP6V1B1 gene [11.1% of patients with DRTA and 27.3% of patients with DRTA and hearing loss]. This study indicated that a significant percentage of the children with DRTA had sensorineural hearing loss and mutation in ATP6V1B1 gene. It is recommended to investigate hearing impairment in all children with DRTA

Restrictive dermopathy. Molecular diagnosis of restrictive dermopathy in a stillborn fetus from a consanguineous Iranian family

Restrictive dermopathy RD, is an autosomal recessive lethal human genetic disorder. It is characterized by intrauterine growth retardation, tight and rigid skin with erosions, multiple joint contractures, lung hypoplasia, prominent superficial vasculature, and epidermal hyperkeratosis. In the present report, we describe the first case of restrictive dermopathy in a stillborn fetus of Iranian origin, confirmed by molecular genetic diagnosis. In the index case G-30159, a homozygous one base insertion in ZMPSTE24 exon 9 c.1085-1086insT was identified.We believe that by increasing awareness of this disease in clinicians, gynecologists, and pathologists, we may be able to help families who have had suspected cases of restrictive dermopathy be diagnosed, and offer molecular testing in carriers, and prenatal diagnosis to prevent the occurrence of further affected cases

case of megalencephalic leukoencephalopathy with subcortical cysts in an iranian consanguineous family

Megalencephalic leukoencephalopathy with subcortical cysts [MLC] is an autosomal recessive disorder characterized by macrocephaly, and slowly progressive clinical course marked by ataxia, spasticity and mental decline. MLC is caused by mutations in the gene MLC1 which encodes a novel protein, MLC1. A 4-year-old girl with macrocephaly, spasticity, ataxia and abnormal cerebral white matter and subcortical cysts in brain MRI diagnosed with MLC. This is the first report of MLC in an Iranian family. MLC1 should be considered in children with macrocephaly and slowly progressive psychomotor decline. This disease can be prenatally diagnosed and genetic counseling offered for future pregnancies

[ review on prenatal screening and diagnosis]

With significant improve in health-care and treatment of infectious diseases, genetic disorders have created a new era of notification. Changes in social attitude towards family life and tendency of parents for limited number of children, sense of responsibility of parents for mental and physical healthiness of children along with their education, needed a new strategy. Since most genetic disorders did not have definitive treatments, physicians tried to prevent these disorders and their disabilities. Early diagnosis of these diseases started in 1934, and first prenatal diagnosis [amniocentesis] was reported in 1967. Rapid progress in cytogenetic and molecular genetic, necessitates each major medical center to have a "prenatal diagnosis department". The first amniocentesis in Iran was done in 1988 with a delay of 20 years. Different problems including no permission for abortion, lack of public knowledge especially authorities and physicians about provided services, and financial limitations of families to afford the expenses of laboratory tests, all were major obstacles to use this technology. Gradually, most of these problems have been solved, and nowadays many centers throughout the country provide these services. In this article, a short list of 15,600 prenatal diagnoses [amniocentesis, chorionic villus sampling, etc] including 13,225 chromosomal abnormalities, 1786 hemoglobinopathies, 283 myopathies, 197 metabolic disorders, 171 triple nucleotide repeats, 32 rare diseases, and eight dermatologic diseases are presented. From 6,473 performed amniocenteses [from 21 February 2007 to 11 April 2009] for evaluation of chromosomal abnormalities, 230 [3.6%] chromosomal abnormalities and 12 [0.2%] unsuccessful responses were documented. In other cases, except for a very few ones who ended in spontaneous abortion, pregnant women continued their pregnancy. Samplings of the amniotic fluid and the placenta were derived by experienced specialties with a very few complications [0.2%], and misdiagnosis was nearly zero

[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

[Pierson syndrome congenital nephritic syndrome with ocular abnormalities: report of an Iranian affected family]

Pierson syndrome is an autosomal recessive disease characterized by congenital nephrotic syndrome, eye and variable neurological abnormalities. Recently mutations in LAMB2 gene were identified as the molecular cause of Pierson syndrome. In this article, we report on an Iranian family with three offspring affected with Pierson syndrome, in which two were molecularly investigated and a novel homozygous mutation in LAMB2 was identified. We believe that Pierson syndrome should be considered in all infants with congenital nephrotic syndrome, particularly-but not exclusively-if it is associated with ocular anomalies. We recommend molecular investigation of the LAMB2 gene for all infants with congenital nephrotic syndrome who are negative for mutations in the NPHS1 gene defining the congenital nephrotic syndrome, Finnish type

[Pfeiffer syndrome: report of a case]

Pfeiffer syndrome is one of craniosynostoses syndromes with autosomal dominant inheritance. Clinical findings are craniosynostoses of coronal sutures with ocular hypertelorism, shallow orbits, proptosis, parrot noese, Broad thumbs and big toes and conductive hearing loss. FGFR2 and rarely FGFR1 are the causing genes.In this article, we are reporting a 2 years old boy with abnormal skull, hypertelorism, proptosis, broad thumbs and toes. He is the only child of normal and unrelated parents. The diagnosis based on clinical findings and confirmed by molecular genetic study

[Chromosomal abnormality and genetics factors in recurrent pregnancy loss]

Pregnancy loss is a common problem in reproductive-aged women. Although most cases of pregnancy loss are sporadic, some couples experience recurrent pregnancy loss. A variety of possible etiologies have been described for recurrent pregnancy loss. In most cases, the cause is not apparent and often requires intensive and expensive clinical and laboratory investigations, despite which there is still a limited understanding of it. This review focuses on the genetic abnormalities that may contribute to this clinical problem and delineates strategies for genetic evaluation and clinical management in subsequent pregnancies

[Craniosynostosis in a patient with 2q37.3 del 5q34dup: association of extra copy of MSX2 with craniosynostosis]

We report a 1-year-old boy with craniosynostosis, microcephaly, developmental delay and dysmorphic features. His karyotype was 46,XX,add2q. Chromosomal study of parents was normal. The imbalance on chromosome 2 in the patient was further defined using comparative genomic hybridization [CGH], which revealed a loss of material from 2q37.3-qter and a gain of 5q34-qter. Florescent in situ hybridization [FISH] studies using subtelomeric 2q and 5q were used to confirm 2q deletion and 5q duplication. It demonstrated 3 signals for 5q terminal and 1 signal for 2q terminal. FISH studies of parents were normal. Recently it has been proposed that an extra copy of the MSX2 gene that is mapped to 5q35.2 causes premature synostosis of the sutures via the MSX2-mediated pathway of calvarial osteogenic differentiation. Our case gives further support of the role of extra copy of MSX2 gene leading to craniosynostosis

[ new case of acro-cardio-facial syndrome: further evidence for clinical variability]

We are reporting a 25 year old man with minor facial and genital anomalies and bilateral ectrodactyly. His parents are first cousins and are both healthy. Facial manifestations included hypertelorism, short down-slanted palpebral fissures, small low-set ears and high forehead. Genital anomalies were undescended right testicle, micropenis and hypospadias. There were four fingers in both hands with a feature of cleft deformity and bone hypoplasia. His sister died four days after birth with severe limb defects and imperforate anus

[Aspects of Greig cephalopolysyndactyly syndrome in a patient with 7pl3pl5 deletion]

A 1-month-old infant with some aspects of Greig cephalopolysyndactyly syndrome [GCPS] and additional features is described. High-resolution chromosomal analysis showed a de novo interstitial deletion of chromosome 7p with breakpoints located at p13 and p15. Our case has some additional features of GCP syndrome, such a cleft palate, narrow auditory canal, umbilical hernia, inguinal hernia, hirsutism, sacral dimple and small skin tag above natal cleft. Frontal bossing, macrocephaly, and high forehead, features associated with GCP was absent in our patient. Hirsutism has been previously reported in only 5 patients with 5p13 deletion. Based on those cases, it has been suggested that the responsible gene might be located in that region. Our patient gives further evidence of this hypothesis