We present the first report of ovarian dysgerminoma in Cowden syndrome, presenting in a 7-year-old girl. In her second decade, a hamartomatous soft tissue extremity mass and diffuse gastrointestinal hamartomatous polyposis with pathologic features suggestive of either juvenile, Peutz-Jeghers, or Cowden polyps were identified, along with diffuse esophageal glycogenic acanthosis ...

Hydrolethalus syndrome is a lethal malformation syndrome with a severe brain malformation, most often hydrocephaly and absent midline structures. Other frequent findings are micrognathia, polydactyly, and defective lobation of the lungs. Hydrolethalus syndrome is inherited in an autosomal recessive manner and is caused by a missense mutation in the HYLS1 ...

Copper is a cofactor for many cellular enzymes and transporters. It can be loaded onto secreted and endomembrane cuproproteins by translocation from the cytosol into membrane-bound organelles by ATP7A or ATP7B transporters, the genes for which are mutated in the copper imbalance syndromes Menkes disease and Wilson disease, respectively. Endomembrane ...

The Waardenburg syndromes (WS) account for approximately 2% of congenital sensorineural deafness. This heterogeneous group of diseases currently can be categorized into four major subtypes (WS types 1-4) on the basis of characteristic clinical features. Multiple genes have been implicated in WS, and mutations in some genes can cause more ...

We report on an infant boy with congenital hydrocephalus due to L1 syndrome and polyuria due to diabetes insipidus. We initially believed his excessive urine loss was from central diabetes insipidus and that the cerebral malformation caused a secondary insufficient pituitary vasopressin release. However, he failed to respond to treatment ...

BACKGROUND: The cerebro-oculo-facio-skeletal syndrome (COFS syndrome) is an autosomal recessive disorder which was initially described in a specific aboriginal population from Manitoba. In recent years, COFS syndrome has been linked in this original population to a defective DNA repair pathway and to a homozygous mutation in the major gene underlying ...

This paper describes the manifestation in a child of a new syndrome characterized by unusual, severe, persistent hyponatremia associated with hyposmolarity, euvolemia, inappropriately concentrated urine and elevated natriuresis. This is the fourth case of this syndrome reported to date, and the first to be reported in a neonate. The clinical ...

Reported here is a 2-year-old girl who was diagnosed to have thiamine-responsive megaloblastic anemia during evaluations for her bilateral neurosensorial deafness. Besides reporting a new mutation on the gene SLC19A2 for the first time in the literature, we highlight the recognition of this syndrome--when megaloblastic anemia and diabetes mellitus coexists--and ...

Keratitis ichthyosis deafness syndrome is a rare congenital ectodermal disorder. It appears to be genetically heterogeneous and may be caused by mutations in the connexin 26 (Cx26) gene (GJB2) or in the connexin 30 gene. It is characterized by the association of ichthyosis-like skin lesions, hearing loss, and vascularizing keratitis. ...

Myeloproliferative diseases represent a major risk factor for Budd-Chiari syndrome. In 32 patients with Budd-Chiari syndrome, the JAK2 V617F mutation was detected, in heterozygous state, in 11 individuals (34.4%; 95% confidence interval: 18.6-53.2). Eight patients with (72.7%; 95% confidence interval: 39.0-94.0) and six without (28.6%; 95% confidence interval: 11.3-52.2) the ...

Dyskeratosis congenita (DC) is a rare syndrome, characterized by cutaneous abnormalities and premature death caused by bone marrow failure. In this issue of Genes & Development, Hockemeyer and colleagues (pp. 1773-1785) report a new mouse model that reconstitutes key features of DC. Disease phenotypes are generated by a POT1b deletion ...

Over the past ten years, several studies demonstrated the connections between cilia, basal bodies and human diseases with a wide phenotypic spectrum, including randomization of body symmetry, obesity, cystic kidney diseases and retinal degeneration. Alstr?m syndrome (OMIM 203800) first described in 1959, is a rare autosomal recessive disorder caused by ...

PURPOSE: Papillorenal syndrome is an autosomal dominant entity due to PAX2 gene mutation, involving optic nerve and renal malformations. METHODS: The authors report a 19-year-old man with bilateral macular detachment associated with optic nerve pit in one eye and morning glory syndrome in the other eye. The patient underwent three-port ...

Werner syndrome is a syndrome which accelerates the normal aging process of an individual. The Syndrome is caused by mutations in the WRN gene. The precise link between this mutated gene and the phenotype is still unclear but much science has been done. By making this report I got an ...

The Werner syndrome protein (WRN) is mutated in Werner syndrome (WS) and plays a role in telomere maintenance, DNA repair and transcription. WS represents a premature aging syndrome with severe growth retardation. Here we show that WRN is critically required to mediate the stimulatory effect of vascular endothelial growth factor ...

Male infertility is one possible consequence of a group of disorders arising from dysfunction of cilia. Ciliopathies include primary ciliary dyskinesia, polycystic kidney disease, Usher syndrome, nephronophthisis, Bardet-Biedl syndrome, Alstrom syndrome, and Meckel-Gruber syndrome as well as some forms of retinal degenerations. Mutations in the retinitis pigmentosa GTPase regulator gene ...

Mitochondrial disorders, in particular respiratory chain diseases (RCDs), present either as single organ problem or as multi-system disease. One of the most frequently affected organs in RCDs, in addition to the skeletal muscle, is the central nervous system (CNS). CNS manifestations of RCDs include epilepsy, stroke-like episodes, migraine-like headache, ataxia, ...

Omenn syndrome is a form of severe combined immunodeficiency associated with erythrodermia, hepatosplenomegaly, lymphadenopathy, and alopecia. Inherited hypomorphic mutations in the recombination activating genes 1 and 2 (RAG1 and RAG2) and in ARTEMIS genes and more recently defects in IL7RA, and RMRP genes have been described to be responsible of ...

Rett syndrome is a severe neurodevelopmental disease caused by mutations in the X-linked gene encoding for the methyl-CpG-binding protein MeCP2. Here, we report the identification of FOXG1-truncating mutations in two patients affected by the congenital variant of Rett syndrome. FOXG1 encodes a brain-specific transcriptional repressor that is essential for early ...

The triple A syndrome is a rare autosomal recessive disease that is characterised by the triad of adrenocorticotropin (ACTH)-resistant adrenal insufficiency, achalasia and alacrima. In most patients, neurological and dermatological abnormalities are associated features. We report on the first Bosnian patient with triple A syndrome. Endocrine investigation confirmed primary adrenal ...

We report the identification of a novel mutation at a highly conserved residue within the N-terminal region of spermine synthase (SMS) in a second family with Snyder-Robinson X-linked mental retardation syndrome (OMIM 309583). This missense mutation, p.G56S, greatly reduces SMS activity and leads to severe epilepsy and cognitive impairment. Our ...

Gitelman's syndrome is an autosomal recessive disorder caused by various mutations of the thiazide- sensitive sodium chloride cotransporter gene. Hypokalaemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria are major clinical features of the syndrome. The onset of the disease is in early adulthood with a mild muscle weakness complaint or incidentally diagnosed ...

Knobloch syndrome (KNO) is a rare autosomal recessive condition caused by pathogenic mutations in the COL18A1 gene. It is characterized by high myopia, vitreoretinal degeneration, retinal detachment and midline encephalocoele or midline occipital bone defect. We report a case of KNO confirmed by direct sequence analysis of the COL18A1 gene ...

Although Noonan syndrome (NS) is occasionally associated with embryonal solid tumors, there has been no report of hepatoblastoma in NS. We identified hepatoblastoma spreading into bilateral hepatic lobes in a 1-month-old NS patient with a heterozygous PTPN11 mutation (Asn308Asp). This finding suggests the potential relevance of constitutively activated RAS/MAPK signaling ...

Gilbert's syndrome is characterized by mild unconjugated nonhemolytic hyperbilirubinemia, which does not lead to hepatic inflammation, fibrosis, chronic liver disease or liver failure. Almost 100 years after its clinical description, it was linked to a genetic variant of the human bilirubin UDP-glucuronosyltransferase (UGT1A1), UGT1A1 (*)28, found in approximately 40% of ...

HPT-JT syndrome is a rare disease characterized by parathyroid tumours (with a high percentage of carcinomas), jaw and kidney tumours. In this thesis, the clinical and genetic features of the HPT-JT syndrome and the relationship between the HRPT2 gene and parathyroid tumours were investigated. We report the identification of the ...

BACKGROUND: We undertook a genome wide single nucleotide polymorphism analysis of a spectrum of patients with myelodysplastic syndrome del(5q) in order to investigate whether additional genomic abnormalities occur. Single nucleotide polymorphism array analysis has been shown to detect not only gene deletions but also regions of uniparental disomy that can ...

MtDNA instability is associated with a wide spectrum of clinical presentations, from dominant or recessive progressive external ophthalmoplegia (PEO) to juvenile-onset spino-cerebellar ataxia and epilepsy (SCAE) or infantile Alpers-Huttenlocher syndrome. We present here the clinical and molecular features of a patient with a clinical presentation characterized initially by PEO with ...

More than 11 genetic causes of severe combined immunodeficiency (SCID) have been identified, affecting development and/or function of T lymphocytes, and sometimes B lymphocytes and natural killer (NK) cells. Deletion of 22q11.2 is associated with immunodeficiency, although less than 1% of cases are associated with T-B + NK + SCID ...

POEMS syndrome is a rare plasma cell disorder characterized by peripheral neuropathy, monoclonal gammopathy, and high levels of serum vascular endothelial growth factor, the pathogenesis of which remains unclear. A unique feature of this syndrome is that the proliferating monoclonal plasma cells are essentially lambda-restricted. Here we determined complete nucleotide ...

We report a family in which two siblings presented with an apparent dysmorphic syndrome, including hypotelorism, blepharophimosis, slight ptosis, epicanthal folds, microstomia and dysmorphic ears. One sibling had a cleft palate. Initially, blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES) was suspected; however, mutation of the FOXL2 gene was not detected. ...

Angelman syndrome is a neurodevelopmental disorder characterized by mental retardation, absence of speech, seizures, abnormal electroencephalography (EEG), and happy disposition. The syndrome results from lack of function of the maternal copy of the UBE3A gene on the imprinted Prader-Willi/Angelman syndrome critical region; it is caused by large deletions, paternal uniparental ...

We describe nine previously unreported individuals from six families who have homozygous mutations of HOXA1 and either the Bosley-Salih-Alorainy syndrome (BSAS) or the Athabascan brainstem dysgenesis syndrome (ABDS). Congenital heart disease was present in four BSAS patients, two of whom had neither deafness nor horizontal gaze restriction, thus raising the ...

Abnormal nuclear megakaryocytic staining for phospho-STAT5 (pSTAT5) correlates with JAK2 V617F mutational status in non-chronic myelogenous leukemia chronic myeloproliferative disorders. However, a proportion of wild-type JAK2 non-chronic myelogenous leukemia chronic myeloproliferative disorders cases also demonstrate this abnormal pSTAT5 expression pattern. We report a patient with a JAK2 V617F-negative myeloproliferative/myelodysplastic syndrome ...

Netherton syndrome is a rare genodermatosis characterized by ichthyosiform scaling, hair shaft abnormalities, and atopic features. Affected infants typically have delayed growth and development, immune abnormalities with recurrent infections, and intermittent aminoaciduria. We report a 23-day-old girl who presented with severe primary pulmonary hypertension, exfoliative erythroderma, and trichorrhexis invaginata. Genetic ...

Fraser syndrome (MIM 219000) is a rare genetic disorder with major features including cryptophthalmos, syndactyly, and genital anomalies. We report 2 independently autopsied children of the same nonconsanguineous parents. The siblings exhibit similar clinical features, all of which are consistent with a diagnosis of Fraser syndrome. The gross and microscopic ...

Hereditary thrombotic thrombocytopenic purpura (TTP) is a rare disorder characterized by occlusive microvascular thrombosis, consumptive thrombocytopenia, and microangiopathic hemolytic anemia. Homozygous or compound heterozygous mutations in the ADAMTS13 gene result in a congenital severe ADAMTS13 deficiency and subsequent accumulation of ultra-large von Willebrand factor multimers, which tend to form platelet ...

Mowat-Wilson syndrome (MWS) is an autosomal dominant developmental disorder with mental retardation and variable multiple congenital abnormalities due to mutations of the ZEB2 (ZFHX1B) gene at 2q22. MWS was first described in 1998 and the causative gene was delineated in 2001. Since then, 115 different mutations of ZEB2 have been ...

BACKGROUND: A 9-month-old boy with Proteus syndrome and a de novo germline mutation in the tumor suppressor PTEN was referred to a specialist centre for management. Over the first years of life, the patient developed life-threatening respiratory dysfunction and malnutrition because of progressive growth of hamartomas affecting the chest, mediastinum, ...

Noonan syndrome is an autosomal dominant disorder with an estimated incidence of 1 in 1,000 to 1 in 2,500 live births. It is characterized by postnatal-onset short stature, characteristic facial changes, webbed neck, pectus carinatum, or excavatum, congenital heart defects, and bleeding abnormalities. Gain-of-function mutations in the PTPN11, KRAS, SOS1, ...

Griscelli syndrome is a rare autosomal recessive disorder. It is characterized by pigment dilution and variable immune deficiency leading to increased susceptibility to certain infections and a tendency to develop a life-threatening hemophagocytic syndrome known as the accelerated phase. Griscelli syndrome is now classified into 3 types based on the ...

Neonatal Marfan syndrome is a severe form of the syndrome mostly caused by de-novo mutations in the fibrillin-1 gene. We report a newborn with neonatal Marfan syndrome and functional pulmonary atresia who died from congestive heart failure on postnatal day 22 despite treatment. He had a mutation in exon 29 ...

Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer, is the most common form of hereditary colorectal cancer. It is characterized by early onset of colorectal cancer and other extracolonic-associated malignancies. This disorder is inherited in an autosomal dominant pattern and is due to a mutation in one of the ...

Cardiac sodium channel dysfunction caused by mutations in the SCN5A gene is associated with a number of relatively uncommon arrhythmia syndromes, including long-QT syndrome type 3 (LQT3), Brugada syndrome, conduction disease, sinus node dysfunction, and atrial standstill, which potentially lead to fatal arrhythmias in relatively young individuals. Although these various ...

Allan-Herndon-Dudley Syndrome (AHDS) is a rare X-linked disorder caused by mutation in the gene encoding the monocarboxylate transporter-8. Abnormal transport function is reflected by elevated free T3 and decreased free T4 levels along with clinical features characterized by neurological abnormalities including global developmental delay, central hypotonia, rotatory nystagmus, impaired hearing, ...

We report on a new family with Teunissen-Cremers syndrome. The proband presented with congenital conductive hearing loss due to stapes ankylosis and incus short process fixation with skeletal anomalies including symphalangism, broad thumbs and broad first toes, syndactyly, brachydactyly, contractures of the elbows and knees, hyperopia and lens opacities. This ...

Costello syndrome is a rare congenital disorder typically characterized by severe failure-to-thrive, cardiac abnormalities including tachyarrhythmia and hypertrophic cardiomyopathy, distinctive facial features, a predisposition to papillomata and malignant tumors, neurologic abnormalities, developmental delay, and mental retardation. Its underlying cause is de novo germline mutations in the oncogene HRAS. Almost all ...

We report on a 5-year-old boy with spondylocarpotarsal synostosis (SCT) syndrome who presents with disproportionate short stature, thoracic scoliosis, pes planus, dental enamel hypoplasia, unilateral conductive hearing loss and mild facial dysmorphisms. Radiographs showed abnormal segmentation of the spine with block vertebrae and carpal synostosis. In addition to the typical ...

BACKGROUND: Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant disorder with an incidence of 1:200 000. Genotype and phenotype are heterogeneous and clinical morphology impresses with variable expressivity. Additionally to the typical craniofacial and dental aberrations anomalies in the morphology of sella turcica are discussed. METHOD: In a multidisciplinary genetic ...

BACKGROUND: Alport syndrome is the most common form of hereditary nephritis and is mainly caused by mutations in the COL4A5 gene, which shows the X-linked form. It is well known that some male Alport syndrome cases show a relatively mild phenotype, but few molecular investigations have been conducted to clarify ...