Alpha-mannosidosis is an extremely rare autosomal recessive genetic condition that affects approximately 1 in 500,000 to 1 in 1,000,000 live births worldwide, and is caused by a mutation in the MAN2B1 gene, which encodes the lysosomal enzyme alpha-mannosidase. It may be suspected in patients under ten years of age who present with speech delay, hearing loss, and skeletal alterations. In patients over ten years of age, motor impairment and psychological manifestations are observed. This report describes an ultra-rare case of a young patient diagnosed with alpha-mannosidosis, as well as the challenges of diagnosis and treatment in a developing country.
With over 8000 rare diseases identified and treatments available for only a fraction, the urgency for accelerating therapeutic development is paramount. Drug repurposing – the process of identifying new uses for existing drugs – may offer a faster, more cost-effective approach than de novo drug development. Thus, the concept of drug repurposing for rare diseases was a hot topic during the RE(ACT) Congress and IRDiRC Conference held in Brussels on March 5–7, 2025. This article draws from the expert panel presentations and discussions, exploring the landscape of drug repurposing in rare diseases, including the opportunities, challenges, and examples of success. Key themes include collaborative infrastructure, data-driven innovation, patient-centricity, and the need for tailored regulatory and commercial strategies.
The 2025 Connect & Collaborate Okur–Chung Neurodevelopmental Syndrome (OCNDS) Scientific and Family Conference convened researchers, clinicians, and families to accelerate discovery and translation of research for OCNDS. OCNDS is an ultra-rare disorder caused by pathogenic variants in the CSNK2A1 gene. Nearly 200 participants joined the 4-day event featuring 17 scientific talks, 15 family sessions, and multiple roundtables integrating patient and researcher perspectives. Scientific sessions covered CK2 biology, variant functional studies, model organism pipelines, and early therapeutic exploration. Family sessions emphasized speech and language outcomes, sleep and behavioral challenges, and barriers to clinical care. Crowdsourced researcher-family dialogues identified shared priorities for the next research phase, including developing measurable clinical endpoints, expanding biobanking and variant data infrastructure, and focusing on translational models to enable preclinical testing. These priorities will steer the next several years of OCNDS research and collaboration, driving coordinated advances toward clinical translation.
With increasing use of prenatal screening, sex chromosome aneuploidies (SCAs) are more frequently detected. Individuals with SCAs have variable physical and medical findings, and developmental and behavioural outcomes. This retrospective study describes the growth, development and clinical features of individuals with SCAs seen at the Genetics clinic in KK Women’s and Children’s Hospital, Singapore, between January 2011 and July 2014. Forty-seven patients were included in this study, comprising six groups: 47, XXY (Klinefelter syndrome); 47, XXY/46, XY; 47, XYY; 47, XYY/46, XY; 47, XXX; and other rare SCAs. The majority (39 patients, 82.9%) were detected prenatally. A developmental assessment was available for 44/47 (93.6%). Of these, 28 (63.6%) were delayed in at least one domain, though the delay was mild in the majority (17 patients) with improvement documented on follow-up. Among eight individuals diagnosed postnatally, global developmental delay was reported in 4 (50%), compared to none among those diagnosed prenatally. Growth appeared unaffected in most, with 11.9% (5 patients) having tall stature. While 63.6% of our patients had developmental delay in at least one domain, commonly affecting speech and language, the delay was mild in the majority. No prenatally diagnosed patient had global developmental delay. This information is valuable in genetic counselling, especially prenatally. (201 words).
Trisomy 18 (Edwards syndrome) and trisomy 13 (Patau syndrome) have historically been regarded as “uniformly lethal” or “incompatible with life,” leading to the longstanding practice of withholding resuscitation and surgical intervention. However, accumulating evidence indicates that survival is more heterogeneous than previously recognized, and advances in neonatal and surgical care have improved outcomes. Among long-term survivors, gradual yet meaningful developmental progress has been observed, and parental reports describe affected children as happy and deeply valued members of their families. These findings have reshaped clinical and ethical perspectives, fostering a paradigm shift from uniform non-intervention toward individualized, family-centered decision-making. In parallel, the widespread adoption of noninvasive prenatal screening (NIPS) has markedly increased prenatal detection, further complicating perinatal counseling and underscoring the need for ethically consistent care. This narrative review summarizes current and evolving evidence on survival and treatment outcomes for trisomy 18 and trisomy 13 and synthesizes contemporary approaches to comprehensive care from the neonatal period through childhood. Within this evolving landscape, we propose a practical framework for counseling and iterative shared decision-making with families. Integrating accurate and up-to-date medical information with family perspectives is essential to provide compassionate, balanced, and equitable care for infants with these syndromes and their families.
