Stone Babies: A Pictorial Essay With Insights From 25 Museal Lithopaedions.

Background: Lithopaedion, or "stone baby," represents an exceptionally rare clinical phenomenon with fewer than 350 documented cases existing in the medical literature. This condition arises when an advanced extrauterine pregnancy ceases its developmental trajectory and undergoes a lithification process, potentially resulting in a calcified mass with fetal-like morphology. Typically, lithopaedions remain asymptomatic for decades, but may occasionally elicit acute symptoms necessitating medical intervention.

Tracheal agenesis versus tracheal atresia: anatomical conditions, pathomechanisms and causes with a possible link to a novel MAPK11 variant in one case.

Background: In this study we aimed to describe the morphological and pathogenetic differences between tracheal agenesis and tracheal atresia, which are not clearly distinguished from each other in the literature, and to contribute thereby to the understanding and management of these conditions. Both tracheal agenesis and tracheal atresia represent rare disorders of still unknown aetiology that cannot be detected by prenatal ultrasound. If the affected foetuses survive until birth these conditions result in respiratory failure and in futile attempts to rescue the infant's life.

Brain malformations in diprosopia observed in clinical cases, museum specimens and artistic representations.

Background: Diprosopus is a rare malformation of still unclear aetiology. It describes a laterally double faced monocephalic and single-trunk individual and has to be distinguished from the variant Janus type diprosopus.

Results: We examined seven double-faced foetuses, five showing true diprosopus, and one each presenting as monocephalic Janiceps and parasitic conjoined twins.

History and highlights of the teratological collection in the Narrenturm, Vienna (Austria).

The collection of the Narrenturm in Vienna houses and maintains more than 50,000 objects including approximately 1200 teratological specimens; making it one of the biggest collections of specimens from human origin in Europe. The existence of this magnificent collection-representing an important resource for dysmorphology research, mostly awaiting contemporary diagnoses-is not widely known in the scientific community. Here, we show that the Narrenturm harbors a wealth of specimens with (exceptionally) rare congenital anomalies.

Prenatal phenotype of PNKP-related primary microcephaly associated with variants affecting both the FHA and phosphatase domain.

Biallelic PNKP variants cause heterogeneous disorders ranging from neurodevelopmental disorder with microcephaly/seizures to adult-onset Charcot-Marie-Tooth disease. To date, only postnatal descriptions exist. We present the first prenatal diagnosis of PNKP-related primary microcephaly.

Compound Heterozygous Frameshift Mutations in MESD Cause a Lethal Syndrome Suggestive of Osteogenesis Imperfecta Type XX.

Multiple genes are known to be associated with osteogenesis imperfecta (OI), a phenotypically and genetically heterogenous bone disorder, marked predominantly by low bone mineral density and increased risk of fractures. Recently, mutations affecting MESD, which encodes for a chaperone required for trafficking of the low-density lipoprotein receptors LRP5 and LRP6 in the endoplasmic reticulum, were described to cause autosomal-recessive OI XX in homozygous children. In the present study, whole-exome sequencing of three stillbirths in one family was performed to evaluate the presence of a hereditary disorder.

Smith-Lemli-Opitz syndrome - Fetal phenotypes with special reference to the syndrome-specific internal malformation pattern.

Autosomal-recessive SLOS is caused by mutations in the DHCR7 gene. It is defined as a highly variable complex of microcephaly with intellectual disability, characteristic facies, hypospadias, and polysyndactyly. Syndrome diagnosis is often missed at prenatal ultrasound and fetal autopsy METHODS: We performed autopsies and DHCR7 gene analyses in eight fetuses suspected of having SLOS and measured cholesterol values in long-term formalin-fixed tissues of an additional museum exhibit RESULTS: Five of the nine fetuses presented classical features of SLOS, including four cases with atrial/atrioventricular septal defects and renal anomalies, and one with additional bilateral renal agenesis and a Dandy-Walker cyst.

Distal Arthrogryposis with Impaired Proprioception and Touch: Description of an Early Phenotype in a Boy with Compound Heterozygosity of Mutations and Review of the Literature.

The recessive -associated disease, distal arthrogryposis with impaired proprioception and touch (DAIPT), is characterized by hypotonia, perinatal respiratory distress, significantly delayed motor milestones, and progressive symptoms of distal arthrogryposis and scoliosis. Here, we describe the youngest patient with DAIPT to date, who, at the age of 3.5 years, did not show a single clinical sign of distal arthrogryposis or contractures, but had a history of bilateral clubfoot operations.

The Opioid Crisis in Missouri: A Call to Action for Physicians, Legislators, and Society.

Opioid overdose deaths in the United States increased sharply over the last decade leading the President to declare a national emergency. The neurobiology of opioid addiction is explored in conjunction with the historical events preceding the current epidemic. A patient-centric perspective is provided along with rationale for contemporary Medical Assisted Therapy (MAT) options to safely reduce overdose deaths and other preventable consequences of prescription misuse and heroin abuse.

Piepkorn type of osteochondrodysplasia: Defining the severe end of FLNB-related skeletal disorders in three fetuses and a 106-year-old exhibit.

The Piepkorn type of lethal osteochondrodysplasia (POCD) is a rare and lethal dwarfing condition. Four cases have been reported to date. The characteristic features are distinctly shortened "flipper-like" limbs, polysyndactyly, excessive underossification, especially of the limb bones and vertebrae, and large (giant) chondrocytes in the cartilaginous bone primordia.

Fetal Pathology of Neural Tube Defects - An Overview of 68 Cases.

Introduction: The prevalence of neural tube defects worldwide is 1 - 2 per 1000 neonates. Neural tube defects result from a disturbance of neurulation in the 3rd or 4th week of development and thus represent the earliest manifestation of organ malformation. Neural tube defects (NTD) are classified into cranial dysraphism leading to anencephaly or meningoencephalocele and spinal dysraphism with or without meningomyelocele.

Mutations in TGDS associated with additional malformations of the middle fingers and halluces: Atypical Catel-Manzke syndrome in a fetus.

Pierre-Robin sequence, radial deviation, and ulnar clinodactyly of the index fingers due to an additional phalangeal bone, as well as heart defects are the key features of Catel-Manzke syndrome. Although mutations in TGDS were identified as the cause of this disorder, the pathogenetic mechanism remains unknown. Here, we report on a fetus with severe heart defect, nuchal edema, talipes, Pierre-Robin sequence, and bilateral deviation and clinodactyly of the index and middle fingers.

De Novo Mutations in SON Disrupt RNA Splicing of Genes Essential for Brain Development and Metabolism, Causing an Intellectual-Disability Syndrome.

The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses conclusively confirming these variants, as well as the underlying molecular mechanisms explaining the diseases, are often lacking. Here, we report on an ID syndrome caused by de novo heterozygous loss-of-function (LoF) mutations in SON.

Dilated, arrhythmogenic cardiomyopathy in emery-dreifuss muscular dystrophy due to the emerin splice-site mutation c.449 + 1G>A.

Objective: Cardiac involvement in X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) usually includes arrhythmias but not dilative cardiomyopathy (dCMP). Here, we report an X-EDMD patient with severe dCMP and life-threatening ventricular arrhythmias associated with other phenotypic features unusual for X-EDMD.

Case Report: A 46-year-old patient with X-EDMD due to the known splice-site mutation c.

Hydrocephalus, agenesis of the corpus callosum, and cleft lip/palate represent frequent associations in fetuses with Peters' plus syndrome and B3GALTL mutations. Fetal PPS phenotypes, expanded by Dandy Walker cyst and encephalocele.

Objective: Fetal pathology aims to recognize syndromal patterns of anomalies for goal-directed mutation analyses, genetic counseling, and early prenatal diagnosis in consecutive pregnancies. Here, we report on five fetuses with Peters' plus syndrome (PPS) from two distinct families aborted after prenatal ultrasound diagnosis of hydrocephaly.

Method: We performed fetal autopsies and molecular analyses.

Klinefelter twins presenting with discordant aneuploidies, acardia, forked umbilical cord and with different gonadal sex despite monozygosity.

Objective: A higher frequency of twin births in sibships of Klinefelter syndrome patients and also monozygotic or dizygotic twins, themselves being affected by Klinefelter syndrome have been noted repeatedly. To address this issue, we evaluated type and frequency of twinning among Klinefelter fetuses that we had received for autopsy within a 'Prenatal Diagnosis' program.

Method: We performed fetal autopsies, and genetic analyses on DNA extracted from stained histological slides.

Recurrent Johanson-Blizzard syndrome in a triplet pregnancy complicated by urethral obstruction sequence: a clinical, molecular, and immunohistochemical approach.

We report on a triplet pregnancy of consanguineous parents with one fetus being affected by recurrent Johanson-Blizzard syndrome (JBS). At autopsy in the 35th gestational week, the affected triplet presented with an especially severe and lethal manifestation of the disorder as compared to his elder affected brother and to cases in the literature, thus exemplifying great interfamilial and intrafamilial phenotypic variability. Arhinencephaly and cystic renal dysplasia associated with urethral obstruction sequence were features not described previously in the literature.

Desbuquois dysplasia type I and fetal hydrops due to novel mutations in the CANT1 gene.

We report on three hydropic fetuses of 17, 22 and 25 gestational weeks from three distinct families presenting with Desbuquois dysplasia type 1. All fetuses showed brachymelia and characteristic dysmorphic features. X-ray studies revealed δ-shaped extraphalangeal bones and disease-specific prominence of the lesser trochanter, varying in severity with fetal age.

Individual health services and the denial of health services in German medical practices: prevalence, regional differences and socio-demographic determinants.

Background: Internationally, in many healthcare systems financial pressure has led to the implementation of co-payments, private medical (extra) services and rationing. In Germany, members of statutory health insurances (SHIs) increasingly report the denial of medical services and the offer/demand of privately financed supplementary health services individual health services, (IHSs) in medical practices. The public discussion on both denial and IHSs is chequered, mainly critical, partly polemic.

Individual health services and the limits to service provision in insurance registered German medical practices: patient experiences.

Background: Persons with statutory health insurance (SHI) in Germany increasingly report being denied medical services and being asked to purchase individual health services (IHS). We performed a population-based survey to study the prevalence of this practice, patients' attitudes toward it, and any potential regional differences.

Methods: Systematic samples were drawn from the population registries of Lübeck and Freiburg.

Tetrasomy 12p (Pallister-Killian syndrome): difficulties in prenatal diagnosis.

Purpose: We report a rare case of Pallister-Killian syndrome diagnosed prenatally with increased nuchal translucency during screening for trisomy 21.

Materials And Methods: Echografic and postmortem examination of the fetus, G-banded chromosome and FISH analysis on short- and long-term chorion villous sampling (CVS) culture.

Results And Discussion: Cytogenetic analysis revealed a supernumerary isochromosome 12p after long-term culture whereas a normal cell line was detected in short-term culture only.