Congenital psoriasis is a rare skin disease that can clinically manifest in the oral cavity in many ways. Although manifestations over the skin are frequent, oral manifestations are rare, especially in pediatric patients. A clear family history, proper examination, and investigations are essential to diagnose this condition. This case report aims to highlight the oral and systemic manifestations of a case of psoriasis in a male pediatric patient.

Multicentric osteolysis, nodulosis, and arthropathy (MONA) syndrome is one of the rare genetic skeletal dysplasias, inherited as an autosomal recessive disorder, which predominantly involves carpal and tarsal bones with characteristic osteolytic lesions and can be misdiagnosed as juvenile idiopathic arthritis or rheumatoid arthritis. MONA syndrome includes diseases involving two genes: the matrix metalloproteinase 2 (MMP2) gene and matrix metalloproteinase 14 (MMP14). Both genes are assumed to cause phenotype variants of the same disease. Older patients may manifest some arthritic features, especially in the wrist, and minute pathological fractures can occur as well. These patients may be misdiagnosed as inflammatory arthritis and physicians might prescribe corticosteroid and disease-modifying immunosuppressive agents. Therefore, physicians should carefully evaluate genetic skeletal dysplasia to make a correct diagnosis and avoid unnecessary pharmacological intervention. We report a case of MONA syndrome in an adult female who came to our facility for an intensive rehabilitation program.

BACKGROUND: NOTCH3, a large type I transmembrane receptor expressed on arterial smooth muscle cells and capillary pericytes, features a diverse extracellular domain with 34 epidermal growth factor-like repeats. It exhibits distinct phenotypes due to variant zygosity and type; missense mutations cause CADASIL with cerebral vasculopathy, while null mutations lead to severe congenital manifestations.
METHODS: This report describes two cases with homozygous loss- of- function variants in NOTCH3 along with their clinical manifestations.
RESULTS: These patients presented with a severe congenital phenotype, including eye misalignment, visual impairment, epilepsy, global developmental delay, and subsequent development of pyramidal signs. Biallelic nonsense variants were discovered in both the cases (NM_000435.3:c.2203 C > T (p. [Arg735Ter]). Livedo reticularis was not reported in our cases, although it was present in previously reported patients. Autosomal recessive NOTCH3-related leukodystrophy is usually caused by biallelic null mutations in NOTCH3.
CONCLUSIONS: The phenotype of biallelic null variants is associated with a more severe phenotype than the dominantly inherited form of the disease.

Autosomal recessive keratitis-ichthyosis-deafness syndrome (KIDAR MIM #242150) is a very rare disorder caused by pathogenic loss-of-function variants in the AP1B1 gene. So far, nine patients have been reported in the literature and more clinical descriptions are essential to further delineate the phenotype of KIDAR. Here we report a new patient with KIDAR and compare the clinical findings with those from the other published cases with molecular confirmation. We describe a 14-year-old male born to non-consanguineous parents with unremarkable family history. The patient had fetal ascites, neonatal pancreatic insufficiency with consequent failure to thrive, feeding difficulties, recurrent infections and sepsis. The skin examination was remarkable for an ichthyosis with conspicuous palmoplantar keratoderma, sparse and brittle hair with alopecia on the vertex and slight bilateral ectropion. He had short stature, thin build, frontal bossing, small teeth and prominent abdomen. Additional features were congenital profound bilateral sensorineural deafness, photosensitivity and photophobia. Mild global developmental delay was noted. Persistent mild anemia, neutropenia, thrombocytopenia, and low serum copper, ceruloplasmin and growth hormone were also present. Brain magnetic resonance imaging (MRI) showed cerebral atrophy and thin corpus callosum. Genetic testing revealed a homozygous deletion in the AP1B1 gene, possibly including the same exons as a previously reported deletion. Comparing the phenotypes of all reported individuals, they are highly concordant and major features are enteropathy with feeding difficulties, failure to thrive, ichthyosis, palmoplantar keratoderma, sensorineural deafness and sparse and brittle hair. Here we report other features present in more than one patient that could be part of the phenotypic spectrum and suggest copy number variation analysis to be performed alongside sequencing of the AP1B1 gene in case of suspicion.

Cornea plana (CP) is a rare ocular condition existing in two distinct clinical and hereditary forms: a milder, autosomal dominant type I and a more severe, autosomal recessive type II. The condition is more commonly found in Finnish, Saudi, and Czech families. We report three brothers from a consanguineous marriage that presented with complaints of decreased vision of varying degrees. All three of them have blue, thick, and hazy corneas with shallow anterior chamber depths. The additional features of CP type II were seen in the older two brothers including arcus lipoids, ill-demarcated limbus, and an accommodative squint. They were managed by the correction of refractive errors through spectacles and detailed counseling with follow-up visits to look for progressive complications. The management is mainly centered around optically or surgically correcting the developmental anomalies. This is complimented with proper genetic counseling and regular follow-up visits to look for and manage complications. There are, however, novel therapies that can be considered in these patients including corneal transplants or corneal stromal stem cellular therapies.

Crigler-Najjar syndrome (CNS) type I is a rare genetic disease caused by mutations in the UGT1A1 gene, resulting in a lack of Uridine 5\'-diphospho-glucuronosyltransferase (UDPGT) enzyme. This enzyme is responsible for the glucuronidation and elimination of unconjugated bilirubin from the body. Here we report a two-month-old Saudi girl who presented with persistent unconjugated hyperbilirubinemia, reaching levels as high as 30 mg/dL despite ineffective phototherapy. The diagnosis was confirmed through sequencing, and the patient underwent a successful liver transplant at the age of two months. At the one-year follow-up, the patient is doing well. This case highlights the significance of early detection and appropriate management of CNS, emphasizing the need for prompt intervention to improve patient outcomes and prevent complications. While phototherapy offers some benefits, liver transplantation remains the only definitive treatment for this condition.

Wolfram syndrome is a neurodegenerative disorder caused by pathogenic variants in the genes WFS1 or CISD2. Clinically, the classic phenotype is composed of optic atrophy, diabetes mellitus type 1, diabetes insipidus, and deafness. Wolfram syndrome, however, is phenotypically heterogenous with variable clinical manifestations and age of onset. We describe four cases of genetically confirmed Wolfram syndrome with variable presentations, including acute-on-chronic vision loss, dyschromatopsia, and tonic pupils. All patients had optic atrophy, only three had diabetes, and none exhibited the classic Wolfram phenotype. MRI revealed a varying degree of the classical features associated with the syndrome, including optic nerve, cerebellar, and brainstem atrophy. The cohort\'s genotype and presentation supported the reported phenotype-genotype correlations for Wolfram, where missense variants lead to milder, later-onset presentation of the Wolfram syndrome spectrum. When early onset optic atrophy and/or diabetes mellitus are present in a patient, a diagnosis of Wolfram syndrome should be considered, as early diagnosis is crucial for the appropriate referrals and management of the associated conditions. Nevertheless, the condition should also be considered in otherwise unexplained, later-onset optic atrophy, given the phenotypic spectrum.

The Ehlers-Danlos Syndromes (EDS), a group of hereditary connective tissue disorders, were classified into 13 subtypes in the 2017 International Classification. Recently, a new subtype of EDS called classical-like EDS type 2 (clEDS2), which is caused by biallelic variants in the adipocyte enhancer binding protein 1 (AEBP1) gene, was identified. We describe the 11th patient (9th family) with clEDS2, who was complicated by a critical vascular event (superior mesenteric artery aneurysm and rupture). A next-generation sequencing panel-based analysis revealed compound heterozygous variants in AEBP1: NM_001129.5:c.[2296G>T]; [2383dup], p.[(Glu766*)]; [(Glu795Glyfs*3)]. Light microscopic analyses showed increased interfibrillar spaces in the reticular dermis, a disorganized arrangement of collagen fibers, and decreased collagen content. An electron microscopic analysis showed the presence of collagen fibrils with irregular contours (flower-like appearance) and small collagen fibrils. A biochemical analysis showed reduced secretion of type I and type III procollagen. Clinical and molecular features of the current patient and all previously reported patients were reviewed comprehensively. Manifestations noted in most cases (>80%) included skin features (hyperextensibility, atrophic scars, easy bruising, excessive skin/skin folding, delayed wound healing, translucency, piezogenic papules), skeletal features (generalized joint hypermobility, dislocations/subluxations, pes planus), dental abnormalities, and neuromuscular abnormalities. Critical complications, each occurring in a single case, included superior mesenteric artery multiple aneurysm and rupture, aortic root dilation requiring surgery, and bowel rupture. Most AEBP1 variants were predicted or experimentally confirmed to lead to nonsense-mediated mRNA decay, whereas one variant resulted in a protein that was retained intracellularly and not secreted. Clinical, molecular, pathological, and biochemical features of the current patient, as well as a review of all previously reported patients, suggest the importance of the aortic carboxypeptidase-like protein encoded by AEBP1 in collagen fibrillogenesis.

Many scientific societies have emphasized the importance of evaluating the clinical utility of reproductive carrier screening (RCS). This systematic review aims to assess the clinical utility of RCS and synthesize the outcomes in a meta-analysis.
A total of eleven studies were included. The number of conditions screened in the studies varied from three to 176 and led to the identification of one to 24 high-risk couples (HRCs) per 1,000 screened individuals. Pooled estimations were as follows: the prenatal diagnosis (PND) rate among pregnant HRCs 0.644 (95% CI = 0.364, 0.923), the termination rate among affected pregnancies 0.714 (95% CI = 0.524, 0.904), and the rate of in-vitro fertilization (IVF) with preimplantation genetic testing (PGT) 0.631 (95% CI = 0.538, 0.725). There is a statistically significant decrease in the rates of undertaking PND and termination as the number of screened conditions increases. Carriers of conditions classified as having a more severe impact were found to be more likely to choose termination or IVF with PGT.
Our review suggests that the number and the severity of screened conditions can significantly impact HRCs\' reproductive decisions. Future work needs to investigate the definition of clinical utility and the design of screening panels.

The TNNI3 gene encodes for the cardiac isoform of troponin I, a pivotal component of the sarcomeric structure of the myocardium. While heterozygous TNNI3 missense mutations have long been associated with autosomal dominant hypertrophic and restrictive cardiomyopathies, the role of TNNI3 null mutations has been more debated due to the paucity and weak characterization of reported cases and the low penetrance of heterozygous genotypes. In recent years, however, an increasing amount of evidence has validated the hypothesis that biallelic TNNI3 null mutations cause a severe form of neonatal dilated cardiomyopathy. Here, we expand the case series reporting two unrelated patients afflicted with early onset dilated cardiomyopathy, due to homozygosity for the p.Arg98* TNNI3 variant, which had thus far been documented only in heterozygous patients and apparently healthy carriers, and the recurrent p.Arg69Alafs*8 variant, respectively. A review of previously reported biallelic TNNI3 loss-of-function variants and their associated cardiac phenotypes was also performed.