Crystalline keratopathy following long-term netarsudil therapy.

Purpose: This case report highlights a possible association between netarsudil use and crystalline keratopathy. Observations: Presented here is the case of a 72-year-old woman with primary open-angle glaucoma (POAG) who developed corneal crystalline keratopathy after taking netarsudil for 24 months. The patient's medical history was significant for dry eye syndrome, bilateral ptosis with surgical repair, and atopy (including asthma and various ocular and systemic allergies). The patient had previously undergone surgical repair for bilateral ptosis as well. During the interval between two routine visits, this patient experienced worsening vision with associated eye irritation. Further examination revealed crystal deposits on the anterior corneal surface in the left eye, the only eye undergoing netarsudil treatment. Conclusions and importance: Long-term netarsudil use may be associated with crystalline keratopathy in the anterior stroma, with the potential to cause sight-threatening vision loss if located in the visual axis.

The Tip of the Iceberg: Genotype of Puerto Rican Pediatric Obesity.

Childhood obesity is a significant public health concern, particularly among Hispanic populations. This study aimed to elucidate the genetic predisposition to obesity in Puerto Rican children of Hispanic descent, addressing a notable gap in existing research. A cohort of 103 children with obesity and hyperphagia underwent genetic screening for rare obesity-related variants. Clinical assessments and family history evaluations were conducted to characterize the demographic and clinical characteristics of the cohort. Genetic testing revealed a high prevalence of variants, with 73% of subjects having at least one reported variant. Pathogenic variants, predominantly associated with obesity-related ciliopathies, were identified in 7% of cases. Additionally, 90% of cases had variants of uncertain significance, highlighting the complexity of genetic contributions to obesity. This study emphasizes the critical need for further investigation into the genetic foundations of obesity, particularly within Hispanic communities. The findings emphasize the importance of early medical evaluation, vigilant monitoring for hyperphagia onset, and targeted interventions tailored to the unique genetic landscape of Puerto Rican children. This research provides a foundational framework for future studies to mitigate the impact of genetic obesity within this population.

CFTR-Related Metabolic Syndrome: Genetic Variants Increasing Pancreatitis Risk in the Pediatric Puerto Rican Population.

CFTR-related metabolic syndrome (CRMS) is a novel diagnosis due to widespread use of and advances in the newborn screening (NBS) process for cystic fibrosis (CF) in the United States of America, allowing for the diagnosis of asymptomatic children with CF. Before 2015, a large Puerto Rican pediatric population was not screened for CF in the NBS test. Studies have shown that patients presenting with idiopathic recurrent or chronic pancreatitis have an increased frequency of cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations. We present a retrospective chart review of 12 pediatric cases (n = 12) that were presented to an outpatient community clinic with clinical manifestations associated with CF. The pancreatic insufficiency prevalence (PIP) score was calculated on CFTR mutations. The mutations considered for the calculation of the PIP score were: F508del (c.1521_1523del), V201M (c.601G > A), I507del (c.1519_1521del), and L1335P (c.4004T > C). V201M mutation was classified as mild in both PIP scores, and a correlation with pancreatitis was noted. Clinical manifestations vary in cases with the V201M variant (c.601G > A). One case was diagnosed with CFTR-related disorder (CRD) and recurrent pancreatitis. It is important to consider CRMS or CRD as a differential diagnosis in the pediatric population of Puerto Rico due to the implications and increased risk of pancreatitis and other CF-related complications.

Nasal Nitric Oxide Levels: Improving the Diagnosis of Primary Ciliary Dyskinesia in Puerto Rico.

Primary Ciliary Dyskinesia (PCD) is a rare genetic disease characterized by motile cilia dysfunction with a prevalence of 1 in 16,309 individuals in Hispanic populations. In Puerto Rico, the prevalence of PCD is unknown. Diagnosis of PCD in Puerto Rico is challenging due to the lack of diagnostic technology. Algorithms for PCD diagnosis include clinical history, genetic testing, ciliary biopsy, and nasal Nitric Oxide (nNO) levels. For the first time, this study successfully implemented and measured the nNO levels in subjects with the RSPH4A (c.921+3_921+6del (intronic)) as a diagnostic tool to complement the current algorithm for PCD diagnosis on the island. The nNO level differentiated homozygous subjects with PCD due to the RSPH4A (c.921+3_921+6del (intronic)) founder mutation compared to healthy gender-age matched controls and subjects with VUS or negative genetic testing for PCD. The acquisition of state-of-the-art diagnostic tools such as nNO positively impacted and expanded our current PCD diagnostic capabilities in Puerto Rico for our founder genetic mutation. The addition of nNO technology promotes earlier disease screening and recognition for patients with PCD on the island. The access to nNO helped us to properly characterize the PCD diagnosis for patients with the RSPH4A (c.921+3_921+6del (intronic)). As a result, our findings will allow us to be part of the national PCD foundation registry and represent Puerto Rican Hispanics in future PCD multicentric clinical trials.

The Genetics of Primary Ciliary Dyskinesia in Puerto Rico.

Primary ciliary dyskinesia (PCD) has been linked to more than 50 genes that cause a spectrum of clinical symptoms, including newborn respiratory distress, sinopulmonary infections, and laterality abnormalities. Although the RSPH4A (c.921+3_6delAAGT) pathogenic variant has been related to Hispanic groups with Puerto Rican ancestry, it is uncertain how frequently other PCD-implicated genes are present on the island. A retrospective chart review of n = 127 genetic reports from Puerto Rican subjects who underwent genetic screening for PCD variants was conducted from 2018 to 2022. Of 127 subjects, 29.1% subjects presented PCD pathogenic variants, and 13.4% were homozygous for the RSPH4A (c.921+3_6delAAGT) founder mutation. The most common pathogenic variants were in RSPH4A and ZMYND10 genes. A description of the frequency and geographic distribution of implicated PCD pathogenic variants in Puerto Rico is presented. Our findings reconfirm that the presence of PCD in Puerto Rico is predominantly due to a founder pathogenic variant in the RSPH4A (c.921+3_6delAAGT) splice site. Understanding the frequency of PCD genetic variants in Puerto Rico is essential to map a future genotype-phenotype PCD spectrum in Puerto Rican Hispanics with a heterogeneous ancestry.

Surfactant Protein C Deficiency in a Puerto Rican Adolescent With a Rare SFTPC Genetic Variant.

Surfactant protein C (SP-C) is a hydrophobic lipoprotein necessary for lowering alveolar surface tension and lung defense mechanisms. Defects in its function due to genetic mutations in the SFTPC gene have been increasingly identified in patients presenting with childhood interstitial lung disease. SFTPC mutations are inherited in an autosomal dominant pattern with reduced penetration and variable expressivity, although de novo mutations have also been documented. In this article, we present the case of an oxygen-dependent 13-year-old male with interstitial lung disease and severe pulmonary hypertension. Genetic analysis and lung biopsy confirmed the diagnosis of SP-C deficiency with the rare heterozygous mutation IVS4+2. To our knowledge, this is the first documented case of SP-C deficiency in the Puerto Rican population and the second worldwide with the IVS4+2 genetic mutation.

Allergic Bronchopulmonary Aspergillosis With or Without Asthmatic Symptoms?

Allergic bronchopulmonary aspergillosis (ABPA) is a localized inflammatory airway disease seen in patients sensitized to Aspergillus fumigatus (A. fumigatus) antigens. The disease presents with productive cough, wheezing, episodic fever, as well as central bronchiectasis (CB) and mucus plugs on computed tomography (CT) scans. If treated accordingly, symptoms and pulmonary damage caused by ABPA can be reverted. Currently, the diagnostic criteria for ABPA require the diagnosis of predisposing pulmonary diseases such as asthma and cystic fibrosis (CF) in order to establish the diagnosis. There has been an increasing number of cases reporting ABPA without evidence of past asthmatic history or symptoms. This reflects the need for more sensitive diagnostic tests in order to prevent progression to irreversible lung injury. Here we report a 22-year-old Puerto Rican male who went undiagnosed for ABPA for 12 months due to the absence of asthma or CF history.

Aquagenic Wrinkling of the Palm: A Rare Diagnostic Clue of Cystic Fibrosis and the Response to CFTR-Modulating Therapy.

Aquagenic wrinkling of the palms (AWP), also known as aquagenic palmoplantar keratoderma, is an uncommon dermatosis characterized by transient translucent whitish papules, edema, and hyper-wrinkling of the palms and soles shortly after water immersion. Approximately up to 80% of cases reported are associated with cystic fibrosis (CF) patients and up to 25% with CF carriers. We present the case of a 16-year-old male who complains of new-onset symmetrical edematous wrinkling on his palms associated with brief water exposure. After evaluation and genetic testing, the patient was diagnosed with CF and AWP. While there are numerous theories regarding the pathogenesis of AWP, no consensus has been reached regarding its etiology or relationship with CF. However, given the high prevalence of AWP associated with the genetic disease, physicians should have a high index of suspicion of CF or cystic fibrosis transmembrane regulator (CFTR)-related disease in pediatric patients with this presentation. The presence of AWP as part of the physical examination may help recognize challenging CF cases with uncommon genetic variants. Prompt recognition of CF disease leads to timely initiation of CFTR-modulating therapy, improving the patient's health outcomes and quality of life. In this case, we also present the patient's response to CFTR-modulating therapy and compare with baseline status.