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

[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 beta-fibrinogen-455 G/A 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 beta-Fibrinogen-455 G/A 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 allele frequency of mutant FGB-455 G/A [0.22] 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 FGB-455 G/A 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

[Berardinelli-seip congenital lipodystrophy: report of a case and review of literature]

Berardinelli-Seip congenital lipodystrophy [BSCL] is a rare genetic disorder which is usually diagnosed at birth or soon thereafter, with lipoatrophy affecting the face, trunk and the limbs. Because of the absence of functional adipocytes, lipid is stored in other tissues, including muscles and liver. Affecting individuals develop insulin resistance and about 35% of individuals develop diabetes mellitus. Hepatomegaly secondary to hepatic steatosis occurs in virtually all individuals. Hypertrophic cardiomyopathy is reported in 20-25% of affected individuals and is a significant cause of mortality. We are reporting a 2.5 year old girl with mild mental retardation, tall stature, hirsutism, lipodystrophy, and hepatomegaly. We believe that our patient suffer from Berardinelli-Seip congenital lipodystrophy

[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

[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

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

[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

[Cardiofaciocutaneous syndrome: case report and review of literature]

Cardiofaciocutaneous [CFC] syndrome is a rare genetic disorder. It characterized by a distinctive facial appearance, cardiac and cutaneous abnormalities and mental retardation. The heart defects include pulmonic stenosis, septal defect, hypertrophic cardiomyopathy and rhythm disturbances. Ectodermal abnormalities include sparse, friable and curly hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. We are reporting a 5-year-old boy with mental retardation, bitemporal narrowing, down slanting palpebral fissure, depressed nasal bridge, coarse face, sparse and brittle hair, high frontal hairline, hypohidrotic and dry skin, atopic dermatitis. We believe that our patient is a case of cardiofaciocutaneous syndrome

[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

[ 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

[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

[Dyggve-Melchior-Clausen disease case report and review of literatures]

Dyggve-Melchior-Clausen [DMC] disease is a rare autosomal recessive spondyloepimetaphyseal dysplasia. The main features are short trunk dwarfism, short limbs, and mental retardation. Radiographs show characteristic abnormalities of the spine, epiphyses and metaphyses. Mutation in DMC gene has been found. A 15 year old boy referred to our genetic center with short trunk dwarfism, short limbs, characteristic radiographic findings and mental retardation. His parents are first cousin. He has three affected uncle with same features. We believe our patient is a new xase of Dyggve-Melchrior-Clausen disease

[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

[Seventeen years experience in precise diagnosis and prenatal diagnosis of mucopolysaccharidoses [MPS]]

Upon a scientific collaboration, families having affected offspring suspected for MPS disease were enzymaticaly analyzed. In 82 families the deficit enzymes were detected. Seventy prenatal diagnosis for parous at risk were performed, revealing 53 unaffected and 17 affected fetuses. All families with affected fetuses opted for pregnancy termination. The prenatal result of unaffected newborns confirmed the prenatal diagnosis findings. The summary of clinical findings and epidemiological distribution of MPS disorders and PND results are presented in this short report

Freeman-Sheldon syndrome: report of 6 cases

Freeman-Sheldon syndrome is a morphologically well-defined syndrome that results in a dysmorphic status combining bone anomalies and joint contractures with characteristic facies. FSS [Freeman-Sheldon Syndrome] is also known as craniocarpotarsal dysplasia [or dystrophy], distal arthrogryposis type IIA [DAIIA], whistling face syndrome, and whistling face-windmill vane hand syndrome. The syndrome is an autosomal dominant trait and characterized by flattened, mask-like facies, microstomia, protruding lips [as in whistling], deep-set eyes with hypertelorism, and camptodactyly with ulnar deviation of the fingers and talipes equinovarus. We are reporting 6 cases with this syndrome that were referred to our genetic center from 2000 to 2006 for cytogenetic study and clinical genetic counseling

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