Trophoblastic disease and choriocarcinoma.

Gestational trophoblastic disease (GTD) is a group of diseases associated with pregnancies that demonstrate abnormal development of trophoblastic cells. GTD includes hydatidiform moles (HM) that may continue to further develop into gestational trophoblastic neoplasms (GTN), such as choriocarcinoma (CC). Gestational CC is a malignant mass development that may arise from HM, from other (normal) pregnancies or from other gestational events (such as ectopic pregnancies).

Genotype-phenotype of autosomal dominant polycystic kidney disease in Malta.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of multiple renal cysts causing kidney enlargement and end-stage renal disease (ESRD) in half the patients by 60 years of age. The aim of the study was to determine the genetic aetiology in Maltese patients clinically diagnosed with ADPKD and correlate the clinical features.

Methods: A total of 60 patients over 18 years of age clinically diagnosed with ADPKD were studied using a customized panel of genes that had sufficient evidence of disease diagnosis using next generation sequencing (NGS).

Missense mutations in small muscle protein X-linked (SMPX) cause distal myopathy with protein inclusions.

Using deep phenotyping and high-throughput sequencing, we have identified a novel type of distal myopathy caused by mutations in the Small muscle protein X-linked (SMPX) gene. Four different missense mutations were identified in ten patients from nine families in five different countries, suggesting that this disease could be prevalent in other populations as well. Haplotype analysis of patients with similar ancestry revealed two different founder mutations in Southern Europe and France, indicating that the prevalence in these populations may be higher.

Progressive myoclonus epilepsies-Residual unsolved cases have marked genetic heterogeneity including dolichol-dependent protein glycosylation pathway genes.

Progressive myoclonus epilepsies (PMEs) comprise a group of clinically and genetically heterogeneous rare diseases. Over 70% of PME cases can now be molecularly solved. Known PME genes encode a variety of proteins, many involved in lysosomal and endosomal function.

International consensus recommendations on the diagnostic work-up for malformations of cortical development.

Malformations of cortical development (MCDs) are neurodevelopmental disorders that result from abnormal development of the cerebral cortex in utero. MCDs place a substantial burden on affected individuals, their families and societies worldwide, as these individuals can experience lifelong drug-resistant epilepsy, cerebral palsy, feeding difficulties, intellectual disability and other neurological and behavioural anomalies. The diagnostic pathway for MCDs is complex owing to wide variations in presentation and aetiology, thereby hampering timely and adequate management.

DPH1 syndrome: two novel variants and structural and functional analyses of seven missense variants identified in syndromic patients.

DPH1 variants have been associated with an ultra-rare and severe neurodevelopmental disorder, mainly characterized by variable developmental delay, short stature, dysmorphic features, and sparse hair. We have identified four new patients (from two different families) carrying novel variants in DPH1, enriching the clinical delineation of the DPH1 syndrome. Using a diphtheria toxin ADP-ribosylation assay, we have analyzed the activity of seven identified variants and demonstrated compromised function for five of them [p.

Infantile Hypertrophic Pyloric Stenosis: An Epidemiological Review.

Infantile hypertrophic pyloric stenosis (IHPS) is the most common gastrointestinal disease among infants. IHPS occurs as an isolated condition or together with other congenital anomalies. Association with genetic and environmental factors, bottle feeding, younger maternal age, maternal smoking, and erythromycin administration in the first two weeks of life has been shown.

Survival beyond the perinatal period expands the phenotypes caused by mutations in GLE1.

Mutations in GLE1 underlie Lethal Congenital Contracture syndrome (LCCS) and Lethal Arthrogryposis with Anterior Horn Cell Disease (LAAHD). Both LCCS and LAAHD are characterized by reduced fetal movements, congenital contractures, and a severe form of motor neuron disease that results in fetal death or death in the perinatal period, respectively. We identified bi-allelic mutations in GLE1 in two unrelated individuals with motor delays, feeding difficulties, and respiratory insufficiency who survived beyond the perinatal period.

Diagnosis and management of Silver-Russell syndrome: first international consensus statement.

This Consensus Statement summarizes recommendations for clinical diagnosis, investigation and management of patients with Silver-Russell syndrome (SRS), an imprinting disorder that causes prenatal and postnatal growth retardation. Considerable overlap exists between the care of individuals born small for gestational age and those with SRS. However, many specific management issues exist and evidence from controlled trials remains limited.

EPG5-related Vici syndrome: a paradigm of neurodevelopmental disorders with defective autophagy.

Vici syndrome is a progressive neurodevelopmental multisystem disorder due to recessive mutations in the key autophagy gene EPG5. We report genetic, clinical, neuroradiological, and neuropathological features of 50 children from 30 families, as well as the neuronal phenotype of EPG5 knock-down in Drosophila melanogaster. We identified 39 different EPG5 mutations, most of them truncating and predicted to result in reduced EPG5 protein.

A case of true hermaphroditism presenting as a testicular tumour.

True hermaphroditism represents only 5% cases of all of disorders of sexual differentiation (DSD) and usually present in early childhood with ambiguous genitalia. Occasionally, cases might present later on in adolescence with problems of sexual maturation. Our case report presents a true hermaphrodite with normal male phenotype that presented as a left testicular mass, two years after being diagnosed with Sertoli cell only syndrome in the contralateral testis.

A recurrent de novo mutation in KCNC1 causes progressive myoclonus epilepsy.

Progressive myoclonus epilepsies (PMEs) are a group of rare, inherited disorders manifesting with action myoclonus, tonic-clonic seizures and ataxia. We sequenced the exomes of 84 unrelated individuals with PME of unknown cause and molecularly solved 26 cases (31%). Remarkably, a recurrent de novo mutation, c.

Vici syndrome--a rapidly progressive neurodegenerative disorder with hypopigmentation, immunodeficiency and myopathic changes on muscle biopsy.

Since its first description by Vici et al. [1988], further reports have continued to broaden the clinical phenotype of this rare multisystem disorder. Main features of agenesis of corpus callosum (ACC), hypopigmentation, immunodeficiency/recurrent infections, cataracts, severe failure to thrive, and profound psychomotor delay have been reported in all cases.

Toriello-Carey syndrome with a 6Mb interstitial deletion at 22q12 detected by array CGH.

Toriello-Carey syndrome is a rare multiple congenital anomaly syndrome comprising agenesis of the corpus callosum, telecanthus, short palpebral fissures, abnormal ears, Pierre Robin sequence, and cardiac anomaly. Autosomal recessive inheritance has been hypothesized and chromosome abnormalities have been reported. The present case is a girl with agenesis of the corpus callosum, a large cleft palate, telecanthus, hypertelorism, atrial septal defect, ventricular septal defect, and patent ductus arteriosus.

Screening of ARHSP-TCC patients expands the spectrum of SPG11 mutations and includes a large scale gene deletion.

Autosomal recessive spastic paraplegia with thinning of corpus callosum (ARHSP-TCC) is a complex form of HSP initially described in Japan but subsequently reported to have a worldwide distribution with a particular high frequency in multiple families from the Mediterranean basin. We recently showed that ARHSP-TCC is commonly associated with mutations in SPG11/KIAA1840 on chromosome 15q. We have now screened a collection of new patients mainly originating from Italy and Brazil, in order to further ascertain the spectrum of mutations in SPG11, enlarge the ethnic origin of SPG11 patients, determine the relative frequency at the level of single Countries (i.

Eight previously unidentified mutations found in the OA1 ocular albinism gene.

Background: Ocular albinism type 1 (OA1) is an X-linked ocular disorder characterized by a severe reduction in visual acuity, nystagmus, hypopigmentation of the retinal pigmented epithelium, foveal hypoplasia, macromelanosomes in pigmented skin and eye cells, and misrouting of the optical tracts. This disease is primarily caused by mutations in the OA1 gene.

Methods: The ophthalmologic phenotype of the patients and their family members was characterized.

Defect in dorso-ventral patterning, asplenia, and conotruncus in a spontaneously aborted fetus.

We describe a very unusual combination, and previously unreported, of malformations in an 18-week, spontaneously aborted male fetus. The fetus had a reversed dorsoventral positioning of the head and upper limbs relative to the body axis with the head and both upper limbs directed dorsally, and an abrupt rotation of the vertebral bones at the level of CZ The fetus also had asplenia, single ventricle, and conotruncus. The fetus also had flexion deformities at the wrist, reduction deformity of the left second digit, anomalies in ossification of the bones of the left hand, and bilateral talipes calcaneovalgus.