Timing of Pubertal Development in Boys and Girls With Congenital Heart Defects: A Nationwide Cohort Study.

Background Children with congenital heart defects (CHD) have an increased risk of developmental delay. It remains sparsely investigated if these patients also have a delayed pubertal development. In this nationwide cohort study, we evaluated if CHD was associated with timing of puberty using longitudinally collected data on pubertal milestones.

Metachronous, non-pineal, trilateral retinoblastoma in a patient with a seemingly reduced-expressivity germline deletion.

The clinical course of trilateral retinoblastoma can be unpredictable, and expressivity of germline variants may vary during development. We describe an unexpected fatal case of trilateral retinoblastoma with an intracranial tumor in an unusual location and discuss genetic copy number analyses as a useful diagnostic tool with therapeutic potential.

Migraine-Associated Mutation in the Na,K-ATPase Leads to Disturbances in Cardiac Metabolism and Reduced Cardiac Function.

Background Mutations in gene encoding the Na,K-ATPase α isoform are associated with familial hemiplegic migraine type 2. Migraine with aura is a known risk factor for heart disease. The Na,K-ATPase is important for cardiac function, but its role for heart disease remains unknown.

A novel nonsense variant in associated with malformations in a female fetus.

Pathogenic variants in the  gene located on the X-chromosome have primarily been reported in males with Lujan-Fryns syndrome, Ohdo syndrome and the Opits-Kaveggia syndrome. However, earlier reports of female patients and female mice suggest that deficiency causes severe malformations. We report a novel example of a nonsense variant in a female fetus with severe malformations identified by trio-exome sequencing.

A novel homozygous variant in causes severe IUGR, edema, and cardiomyopathy in two fetuses.

The C1QBP protein (complement component 1 Q subcomponent-binding protein), encoded by the C1QBP gene, is a multifunctional protein predominantly localized in the mitochondrial matrix. Biallelic variants have previously been shown to give rise to combined respiratory-chain deficiencies with variable phenotypic presentation, severity, and age at onset, from intrauterine with a mostly lethal course, to a late-onset mild myopathy. We present two fetuses, one male and one female, of first-cousin parents, with severe intrauterine growth retardation, oligo/anhydramnios, edema, and cardiomyopathy as the most prominent prenatal symptoms.

Cell-based noninvasive prenatal testing (cbNIPT) detects pathogenic copy number variations.

In two cases, cell-based noninvasive prenatal testing (cbNIPT) detected pathogenic copy number variations (CNVs) in the fetal genome. cbNIPT may potentially be an improved noninvasive alternative for the detection of smaller CNVs.

Novel variant causes a severe form of metatropic dysplasia.

We present a girl born with a frontal bossing, short neck, bell-shaped thorax, short limbs with prominent joints, and a tail-like coccygeal appendage. Genetic screening of identified a novel de novo heterozygous missense variant. We believe the variant causes the severe form of metatropic dysplasia in this patient.

A case of penta X syndrome caused by nondisjunction in maternal meiosis 1 and 2.

The prenatal abnormalities in patients with penta X syndrome appear late in pregnancy and are nonspecific. In contrast, the postnatal phenotype is well described although new findings are still revealed. Penta X syndrome is a result of successive nondisjunctions of the X chromosomes in both maternal meiotic divisions.

Isolated congenital hepatic fibrosis associated with mutations: report of a new genotype-phenotype relationship.

We report an otherwise healthy 32-year-old man with portal hypertension, variceal bleeding, and congenital hepatic fibrosis with ductal plate malformation. Genetic screening identified two TMEM67 mutations. Biallelic TMEM67 mutations are known to cause Joubert/Meckel syndrome or nephronopthisis with hepatic fibrosis, but have never been found in isolated hepatic fibrosis.

First reported case of Simpson-Golabi-Behmel syndrome in a female fetus diagnosed prenatally with chromosomal microarray.

Simpson-Golabi-Behmel syndrome (SGBS) is a rare X-linked syndrome. Female carriers may have mild manifestations. Macrosomia, polyhydramnios, and kidney and urinary tract anomalies are common findings in male fetuses.

The role of genes, intelligence, personality, and social engagement in cognitive performance in Klinefelter syndrome.

Introduction: The determinants of cognitive deficits among individuals with Klinefelter syndrome (KS) are not well understood. This study was conducted to assess the impact of general intelligence, personality, and social engagement on cognitive performance among patients with KS and a group of controls matched for age and years of education.

Methods: Sixty-nine patients with KS and 69 controls were assessed in terms of IQ, NEO personality inventory, the Autism Spectrum Quotient (AQ) scale, and measures of cognitive performance reflecting working memory and executive function.

Rothmund-Thomson Syndrome: novel pathogenic mutations and frequencies of variants in the RECQL4 and USB1 (C16orf57) gene.

Background: Poikiloderma is defined as a chronic skin condition presenting with a combination of punctate atrophy, areas of depigmentation, hyperpigmentation and telangiectasia. In a variety of hereditary syndromes such as Rothmund-Thomson syndrome (RTS), Clericuzio-type poikiloderma with neutropenia (PN) and Dyskeratosis Congenita (DC), poikiloderma occurs as one of the main symptoms. Here, we report on genotype and phenotype data of a cohort of 44 index patients with RTS or related genodermatoses.