The COVID‐19 pandemic has led to a reorganization of health systems to prioritize the fight against the virus. The adoption of social distancing interfered with the flow of existing policies, and may thus negatively affect the most vulnerable groups, such as the rare disease community. Aimming at characterizing the perception of the impact of COVID‐19 on the health care of the Brazilian rare disease

In an era of increasing technology and interaction with the patient bedside, we explore the role of relocating the bedside from the hospital to the home using telemedicine. The COVID‐19 pandemic pushed telemedicine from small and pilot programs to widespread practice at an unprecedented rate. With the rapid implementation of telemedicine, it is important to consider how to create a telehealth system

To meaningfully address health disparities in access to genomic testing, major developments in the infrastructure to support delivery of care are needed. The current value chain for delivering genomic medicine is fragmented, with poor communication between the stakeholders who order, perform, and reimburse for genetic tests. Standards, connectivity, and scaled expertise are needed to reach more people

Birth defects are structural or functional defects present at birth and are caused by different factors that affect intrauterine development. They are the second most common cause of death under five years of age in Latin America and the Caribbean. In Bogotá and Cali, Colombia, there are two surveillance programs established to evaluate the prevalence of them. The purpose of the following article is

The COVID‐19 pandemic necessitated a rapid transition from in‐person office visits to virtual visits in the Down syndrome specialty program at Massachusetts General Hospital (MGH DSP). We describe the clinic transition to virtual visits in April 2020 and reflect on our six‐month experience in virtual visits. Clinic metrics were tracked. Electronic survey responses were collected from caregivers attending

GM2 gangliosidosis, Tay‐Sachs and Sandhoff diseases, are lysosomal storage disorders characterized by the lysosomal accumulation of GM2 gangliosides. This accumulation is due to deficiency in the activity of the β‐hexosaminidases Hex‐A or Hex‐B, which are dimeric hydrolases formed by αβ or ββ subunits, respectively. These disorders show similar clinical manifestations that range from mild systemic

We report the clinical and molecular data of a large cohort comprising 242 individuals with RASopathies, from a single Tertiary Center in Brazil, the largest study from Latin America. Noonan syndrome represented 76% of the subjects, with heterozygous variants in nine different genes, mainly PTPN11, SOS1, RAF1, LZTR1, and RIT1, detected by Sanger and next‐generation sequencing. The latter was applied

This article reports the present situation of Brazilian health care in genetics for Orofacial Cleft (OFC) and 22q11.2 Deletions Syndrome (22q11.2 DS) based on research conducted by Brazil's Craniofacial Project (BCFP). Established in 2003, BCFP is a voluntary and cooperative network aiming to investigate the health care of people with these diseases and other craniofacial anomalies. The initiatives

We review studies from our laboratories using different molecular tools to characterize the Amerindian, European and African ancestry of Brazilians. Initially we used uniparental DNA markers to investigate the contribution of distinct Y chromosome and mitochondrial DNA lineages to present‐day populations. High levels of genetic admixture and strong directional mating between European males and Amerindian

Our 25 years of experience in carrier diagnosis of hemophilia A (HA) and B (HB) in Mexican population comprises linkage analysis of intragenic F8/F9 neutral variants along with, in severe HA (SHA), detection of F8 int22h and int1h inversions. In symptomatic carriers (SCs) we explored Lyonization to explain their symtomatology. From a DNA‐Bank of 3,000 samples, intragenic restriction fragment length

Rare diseases comprise a diverse group of conditions, most of which involve genetic causes. We describe the variable spectrum of findings and clinical impacts of exome sequencing (ES) in a cohort of 500 patients with rare diseases. In total, 164 primary findings were reported in 158 patients, representing an overall diagnostic yield of 31.6%. Most of the findings (61.6%) corresponded to autosomal dominant

Most of the geographically isolated island nations in the Caribbean have small populations and low gross national product. As such, many lack important medical and community services. Difficulties are compounded when attempting to care for children with special needs and genetic disorders such as Down syndrome. International charitable organizations can help to provide much needed specialty medical

The aim of this study was to perform 22q11.2 deletion screening and chromosomal microarray analysis (CMA) in individuals clinically diagnosed with craniofacial microsomia (CFM) and review previously published cases of CFM with genomic imbalances. It included 54 individuals who were evaluated by a clinical geneticist. Copy number variants (CNVs) in the 22q11.2 region were investigated by multiplex ligation‐dependent

Skeletal dysplasias (SD) are disturbances in growth due to defects intrinsic to the bone and/or cartilage, usually affecting multiple bones and having a progressive character. In this article, we review the state of clinical and research SD resources available in Latin America, including three specific countries (Brazil, Argentina, and Chile), that have established multidisciplinary clinics for the

There is a shortage of genetics providers worldwide and access is limited to large academic centers. Telemedicine programs can facilitate access to genetic services to patients living in remote locations. The goal of this study was to improve access to genetic services in the Dominican Republic by creating a partnership model between a pediatrician and geneticist. This approach has been used within

We report the case of a 17‐year‐old girl with Tyrosinemia type 1a who carried a planned pregnancy to term while being under 2‐(2‐nitro‐4‐trifluoromethylbenzoyl)‐1,3‐cyclohexanedione (NTBC, nitisinone) treatment and a tyrosine‐ and phenylalanine‐restricted diet. She was on treatment since 2 months of age with poor metabolic control prior to her pregnancy (tyrosine 838 ± 106 umol/L). NTBC and a low tyrosine

Hypertrichosis is a rare condition characterized by excessive hair in areas of the body that are not predominantly androgen dependent. We can identify three main syndromes with congenital generalized hypertrichosis terminalis described in Mexico. The first is X‐linked generalized hypertrichosis, an ultra‐rare disease, with few cases reported to date. The second is Cantú syndrome, also known as hypertrichotic

Mutations in three genes (APP, PSEN1, and PSEN2) are the main cause of the autosomal dominant early‐onset Alzheimer's disease (AD‐EOAD). In PSEN1, the A431E (c.1292C>A, rs63750083) mutation is suspected to have exerted a founder effect in the State of Jalisco, Mexico. In Guadalajara, Jalisco, Mexico, this mutation was found in 46 index cases evaluated for AD‐EOAD. In our genealogical analysis, 301

We describe our experiences with organizing pro bono medical genetics and neurology outreach programs on several different resource‐limited islands in the West Indies. Due to geographic isolation, small population sizes, and socioeconomic disparities, most Caribbean islands lack medical services for managing, diagnosing, and counseling individuals with genetic disorders. From 2015 to 2019, we organized

Our aim was to characterize the phenotype and genotype of individuals with Noonan syndrome in Colombia. There are published cohorts of Noonan individuals from several countries in Latin America including Brazil, Chile, and Argentina, but none from Colombia. We described 26 individuals with NS from a single large referral center in the South West of Colombia using an established database in the genetics

Multiple myeloma is the most common hematological malignancy in Gaucher disease type 1 (GD1). There is a lack of outcome data and consensus regarding screening of gammopathies. This study explores utility of screening in Porto Alegre, Brazil, and Cincinnati, Ohio. A retrospective analysis of clinical information and laboratory data from GD1 patients was performed. Over 19 years, 68 individuals with

We carried out an exhaustive review regarding human skin color variation and how much it may be related to vitamin D metabolism and other photosensitive molecules. We discuss evolutionary contexts that modulate this variability and hypotheses postulated to explain them; for example, a small amount of melanin in the skin facilitates vitamin D production, making it advantageous to have fair skin in an

The early detection of congenital anomaly epidemics occurs when comparing current with previous frequencies in the same population. The success of epidemiologic surveillance depends on numerous factors, including the accuracy of the rates available in the base period, wide population coverage, and short periodicity of analysis. This study aims to describe the Latin American network of congenital malformation

More than 4,000 genes have been associated with recognizable Mendelian/monogenic diseases. When faced with a new diagnosis of a rare genetic disorder, health care providers increasingly turn to internet resources for information to understand the disease and direct care. Unfortunately, it can be challenging to find information concerning treatment for rare diseases as key details are scattered across

Genetic testing can provide definitive molecular diagnoses and guide clinical management decisions from preconception through adulthood. Innovative solutions for scaling clinical genomics services are necessary if they are to transition from a niche specialty to a routine part of patient care. The expertise of specialists, like genetic counselors and medical geneticists, has traditionally been relied

Technology has changed the way we approach medical care: health data is constantly being generated, medical discoveries are progressing more rapidly, and individuals are more connected across the world than ever before. Backpack Health is a global personal health record platform that harnesses the power of technology to connect users to their primary health data sources, the medical community, and

The advent of next generation DNA sequencing (NGS) has revolutionized clinical medicine by enabling wide‐spread testing for genomic anomalies and polymorphisms. With that explosion in testing, however, come several informatics challenges including managing large amounts of data, interpreting the results and providing clinical decision support. We present Flype, a web‐based bioinformatics platform built

The COVID‐19 pandemic disrupted the delivery of healthcare services, including genetic counseling. This study assessed the professional impact of the pandemic on genetic counselors (GCs) and evaluated how genetics service delivery models changed in New York State (NYS). One hundred sixty‐five NYS GCs participated in an anonymous survey. Clinic structure, telegenetics (video and/or telephone consultations)

The genetic and phenotypic heterogeneity of neurogenetic diseases forces patients and their families into a “diagnostic odyssey.” An increase in the variability of genetic disorders and the corresponding gene‐disease associations suggest the need to periodically re‐evaluate the significance of variants of undetermined pathogenicity. Here, we report the diagnostic and clinical utility of Targeted Gene

In this special issue of the American Journal of Medical Genetics, Part C, we explore the ever‐expanding field of Ophthalmic Genetics. The eye is unique among organs for its accessibility to physical examination, permitting exploration of every tissue by slit lamp microscopy, ophthalmoscopy, and imaging including color and autofluorescent photography, ultrasound, optical coherence tomography (OCT)

Inherited retinal dystrophies are a group of monogenic disorders that, as a whole, contribute significantly to the burden of ocular disease in both pediatric and adult patients. In their syndromic forms, retinal dystrophies can be observed in association with intellectual disability, frequently alongside other systemic manifestations. There are now over 80 genes implicated in syndromic retinal dystrophies

Inherited retinal degenerations (IRDs) are a genotypically and phenotypically diverse group of conditions. Great strides have been made toward identifying the genetic basis for these conditions over the last 30 years—more than 270 different genes involved in syndromic and nonsyndromic forms of retinal dystrophies have now been identified. The identification of these genes and the improvement of clinical

Overall, approximately one‐quarter of patients with genetic eye diseases will receive a molecular diagnosis. Patients with developmental eye disorders face a number of diagnostic challenges including phenotypic heterogeneity with significant asymmetry, coexisting ocular and systemic disease, limited understanding of human eye development and the associated genetic repertoire, and lack of access to

Ocular coloboma is a congenital disorder of the eye where a gap exists in the inferior retina, lens, iris, or optic nerve tissue. With a prevalence of 2–19 per 100,000 live births, coloboma, and microphthalmia, an associated ocular disorder, represent up to 10% of childhood blindness. It manifests due to the failure of choroid fissure closure during eye development, and it is a part of a spectrum of

To report ophthalmic findings of patients without colobomas, and with a clinical and molecular diagnosis of CHARGE Syndrome. Retrospective study of ophthalmic findings in 67 CHARGE patients—clinically confirmed diagnosis with positive CHD7 mutation—seen in the Ophthalmology department of Cincinnati Children's Hospital Medical Center between January 1, 2008 through September 25, 2018. Criteria for inclusion

The spectrum of peroxisomal disorders is wide and comprises individuals that die in the first year of life, as well as people with sensorineural hearing loss, retinal dystrophy and amelogenesis imperfecta. In this article, we describe three patients; two diagnosed with Heimler syndrome and a third one with a mild‐intermediate phenotype. We arrived at these diagnoses by conducting complete ophthalmic

Pathogenic variants in the gene HGSNAT (heparan‐α‐glucosaminide N‐acetyltransferase) have been reported to underlie two distinct recessive conditions, depending on the specific genotype, mucopolysaccharidosis type IIIC (MPSIIIC)—a severe childhood‐onset lysosomal storage disorder, and adult‐onset nonsyndromic retinitis pigmentosa (RP). Here we describe the largest cohort to‐date of HGSNAT‐associated

Mosaic genetic mutations may be somatic, germline, or “gonosomal” and have the potential to cause genetic syndromes, disorders, or malformations. Mutations can occur at any point in embryonic development and the timing determines the extent of distribution of the mutation throughout the body and different tissue types. The eye and visual pathway offer a unique opportunity to study somatic and gonosomal

Variants in the PROM1 gene are associated with cone (−rod) dystrophy, macular dystrophy, and other phenotypes. We describe the clinical and genetic characteristics of 10 patients from eight Japanese families with PROM1‐associated retinal disorder (PROM1‐RD) in a nationwide cohort. A literature review of PROM1‐RD in the Japanese population was also performed. The median age at onset/examination of 10

The retinitis pigmentosa 2 (RP2) gene is one of the causative genes for X‐linked inherited retinal disorder. We characterized the clinical/genetic features of four patients with RP2‐associated retinal disorder (RP2‐RD) from four Japanese families in a nationwide cohort. A systematic review of RP2‐RD in the Japanese population was also performed. All four patients were clinically diagnosed with retinitis

Stargardt disease 1 (STGD1) is the most prevalent retinal dystrophy caused by pathogenic biallelic ABCA4 variants. Forty‐two unrelated patients mostly originating from Western China were recruited. Comprehensive ophthalmological examinations, including visual acuity measurements (subjective function), fundus autofluorescence (retinal imaging), and full‐field electroretinography (objective function)

Inherited retinal diseases are clinically heterogeneous and are associated with nearly 300 different genes. In this retrospective, observational study of a consecutive cohort of 159 patients (134 families) with childhood‐onset (<16 years of age) retinal dystrophy, molecular investigations, and in‐depth phenotyping were performed to determine key clinical and molecular characteristics. The most common

Ophthalmic genetics is a much needed and growing area in India. Ethnic diversity, with a high degree of consanguinity, has led to a high prevalence of genetic disorders in the country. As the second most populous country in the world, this naturally results in a significant number of affected people overall. Practice involves coherent association between ophthalmologists, genetic counselor and pediatricians

Leber congenital amaurosis (LCA) and early‐onset retinal dystrophy (EORD) are severe inherited retinal dystrophy that can cause deep blindness childhood. They represent 5% of all retinal dystrophies in the world population and about 10% in Brazil. Clinical findings and molecular basis of syndromic and nonsyndromic LCA/EORD in a Brazilian sample (152 patients/137 families) were studied. In this population

South America comprises of heterogeneous topographies, populations, and health care systems. Therefore, it is not surprising to see differences among the countries regarding expertise, education, and practices of ophthalmic genetics for patients with rare eye diseases. Nevertheless, common challenges such as limited genetics training in medical schools and among ophthalmologists, scarcity of diagnostic

Genetic eye diseases are phenotypically and genetically heterogeneous, affecting 1 in 1,000 people worldwide. This prevalence can increase in populations where endogamy is a social preference, such as in Arab populations. A retrospective consecutive cohort of 91 patients from 74 unrelated families affected with non‐syndromic and syndromic inherited eye disease presenting to the ocular genetics service

The aim of this review is to reveal Turkey's current status of medical practice in inherited eye diseases and the necessary steps to improve healthcare services and research activities in this area. Since consanguinity rate is high, disease burden is estimated to be high in Turkey. Universal health insurance system, easily accessible medical specialists, increasing genetic test, and counseling opportunities

Glaucoma is an important cause of irreversible blindness, characterized by optic nerve anomalies. Increased intraocular pressure (IOP) and aging are major risk factors. Retinal ganglion cells and trabecular meshwork cells are certainly involved in the etiology of glaucoma. Glaucoma is usually a complex disease, and various genes and functions may contribute to its etiology. Among these may be genes

Genetic testing in a multisite clinical trial network for inherited eye conditions is described in this retrospective review of data collected through eyeGENE®, the National Ophthalmic Disease Genotyping and Phenotyping Network. Participants in eyeGENE were enrolled through a network of clinical providers throughout the United States and Canada. Blood samples and clinical data were collected to establish

The Foundation Fighting Blindness is a 50‐year old 501c(3) non‐profit organization dedicated to supporting the development of treatments and cures for people affected by the inherited retinal diseases (IRD), a group of clinical diagnoses that include orphan diseases such as retinitis pigmentosa, Usher syndrome, and Stargardt disease, among others. Over $760 M has been raised and invested in preclinical

Novel therapeutics for inherited retinal dystrophies (IRDs) have rapidly evolved since groundbreaking clinical trials for LCA due to RPE65 mutations led to the first FDA‐approved in vivo gene therapy. Since then, advancements in viral vectors have led to more efficient AAV transduction and developed other viral vectors for gene augmentation therapy of large gene targets. Furthermore, significant developments

Current genetic screening methods for inherited eye diseases are concentrated on the coding exons of known disease genes (gene panels, clinical exome). These tests have a variable and often limited diagnostic rate depending on the clinical presentation, size of the gene panel and our understanding of the inheritance of the disorder (with examples described in this issue). There are numerous possible

Sex chromosome abnormalities (SCAs) are characterized by gain or loss of entire sex chromosomes or parts of sex chromosomes with the best‐known syndromes being Turner syndrome, Klinefelter syndrome, 47,XXX syndrome, and 47,XYY syndrome. Since these syndromes were first described more than 60 years ago, several papers have reported on diseases and health related problems, neurocognitive deficits, and

Since the first description of Klinefelter syndrome (KS) was published in 1942 in The Journal of Clinical Endocrinology , large inter‐individual variability in the phenotypic presentation has been demonstrated. However, our understanding of the global impact of the additional X chromosome on the genome remains an enigma. Evidence from the existing literature of KS indicates that not just one single

One of the two X chromosomes in females is epigenetically inactivated, thereby compensating for the dosage difference in X‐linked genes between XX females and XY males. Not all X‐linked genes are completely inactivated, however, with 12% of genes escaping X chromosome inactivation and another 15% of genes varying in their X chromosome inactivation status across individuals, tissues or cells. Expression