Journals
2026 EN
Giuntini Martina · Picchi Lucia · Cafforio Gianfranco
+4 more
ABSTRACT We present the case of a 61‐year‐old woman with late‐onset hyperkinetic movement disorder, characterized by involuntary, choreiform movements predominantly affecting the right limbs. Symptoms began at age 60 and were exacerbated by emotional stress. Neurological and neurocognitive evaluations were unremarkable, and extensive diagnostic workup, including Magnetic Resonance Imaging (MRI), Electroencephalogram (EEG), Positron Emission Tomography with Fluorodeoxyglucose (FDG‐PET) and genetic testing for common movement disorders, was largely negative. Notably, a heterozygous pathogenic variant (c.736C>T; p.Arg246Trp) in the GLRA1 gene was identified via exome sequencing. This gene encodes a glycine receptor subunit associated with Hyperekplexia (HPX), a rare neurometabolic disorder typically presenting in infancy with exaggerated startle responses. Although our patient did not show a classic HPX phenotype, the clinical picture included emotionally triggered motor symptoms and a positive response to clonazepam, a hallmark of HPX treatment. Clonazepam monotherapy at low doses led to sustained symptom control, while other treatments were less effective. Family history revealed similar late‐onset symptoms in the patient's father, though undocumented. This case expands the phenotypic spectrum of HPX and suggests that atypical presentations may be misclassified as functional neurological disorders. It underscores the importance of genetic evaluation in unexplained adult‐onset movement disorders and raises the possibility of underrecognized late‐onset HPX variants in clinical practice.
Journals
2026 EN
Raski Carolyn R. · Prada Carlos E.
ABSTRACT Smith‐Kingsmore syndrome (SKS) is a rare autosomal dominant condition characterized by neurodevelopmental differences, macrocephaly/megalencephaly, describable facial features, sleep–wake abnormalities, hyperphagia, and overgrowth. SKS is caused by pathogenic gain‐of‐function variants in MTOR which lead to hyperactivation of the mTOR pathway. In this review, we discuss the history, epidemiology, molecular basis, clinical features, and management considerations for Smith‐Kingsmore syndrome. In addition, we provide insight on early developmental milestones through a report on 14 individuals with a confirmed diagnosis of SKS. Among these individuals, 8/12 (67%) achieved crawling at an average age of 23 months, 9/14 (64%) achieved walking with an average age of 32 months, 5/9 (56%) achieved a pincer grasp at an average age of 23 months, 8/12 (67%) achieved the ability to use a device or utensil with an average age of 3.4 years, 10/13 (77%) achieved babbling at an average age of 20 months, 8/14 (57%) achieved their first word at an average age of 34 months, and 4/14 (29%) achieved the use of short phrases at an average age of 4.6 years. This review highlights advances in characterizing the natural history of SKS since it was first described 12 years ago and the need for additional research to inform genotype–phenotype correlations and targeted therapies to support individuals with SKS.
Journals
2026 EN
Cohen Ryan · Ganapathi Mythily · Ziegler Alban
+2 more
ABSTRACT We report an 87‐year‐old female with a history of intellectual disability, severe speech impairment and behavioral issues. She was globally delayed in childhood. In adolescence, she had hallucinations, behavioral issues and was institutionalized. Her behavioral issues were treated, and her medical and behavioral course was stable until her 80's when she began to decline cognitively. She died at age 87. Exome sequencing revealed a novel predicted damaging missense variant (c.1913T>G; p.Met638Arg; NM_001136196.2) in the gene encoding Transportin‐2 ( TNPO2 ). Heterozygous variants in TNPO2 have been recently associated with an intellectual developmental disorder with hypotonia, impaired speech, and dysmorphic facies (IDDHISD; MIM:619556). Postmortem pathological examination of her brain revealed focal neuronal depletion in the dentate gyrus, CA1, and hilar regions of the hippocampus. These findings are consistent with human gene expression data showing normal to increased expression of TNPO2 in the dentate gyrus and CA1 region of the hippocampus. We suggest that the p.(Met638Arg) variant in TNPO2 is potentially disease‐causing and associated with IDDHISD.
Journals
2026 EN
Hickingbotham Madison R. · Bell Megan · Zoltick Emilie S.
+6 more
ABSTRACT Elective genomic testing (EGT) for medically actionable disease predispositions may help adopted individuals (adoptees) with limited knowledge of family health history (FHH) information understand their inherited risks. In this prospective cohort study, patients who participated in Sanford Health's EGT program were surveyed at the time of enrollment between August 2020 and April 2022 about their motivations for pursuing EGT and perceived risks for three conditions. Data from self‐reported adoptees and nonadoptees were analyzed using bivariate analyses. Of the 5799 eligible patients, 197 (3.4%) reported that they were adopted. Adoptees were more likely than nonadoptees to report lack of information about FHH as a very important motivation for pursuing EGT (81% vs. 32%, p < 0.001) and were more likely to rate it as their most important motivation (45% vs. 5%; p < 0.001). Other motivations, including learning about personal disease risk (72% vs. 61%; p = 0.016) and providing disease risk information to children (69% vs. 57%; p = 0.003), were also more likely to be rated as very important by adoptees than by nonadoptees, respectively. No differences in risk perceptions were observed. A lack of FHH information is an important reason why adoptees pursue EGT. Adoptees may hope that EGT will identify inherited risks for disease.
Journals
2026 EN
Canales Cindy Y. · Shields Kathleen · Choates Meagan
+4 more
ABSTRACT Genetic conditions suspected in children often require genetic testing for accurate diagnoses, but testing remains costly. Case management teams review genetic test requests to improve access for patients while reducing the financial burden for medical institutions. Limited data exist on the diagnostic yields of genetic testing in the inpatient versus outpatient setting and the impact to care denial of inpatient genetic testing may pose. This study investigates diagnostic yields between patients approved for versus denied inpatient genetic testing and its impact to care. One thousand and fifty‐two charts of children admitted inpatient who received a genetic consult between July 2018 and June 2023 were reviewed; charts of children that followed up at the outpatient genetics clinic after inpatient discharge were additionally reviewed. Collected data included recommendations, completion, and results of genetic testing, and management recommendations based on a diagnosis. Statistical analysis assessed differences between the groups. Private insurance holders and patients with no prematurity history were less likely to be approved for inpatient genetic testing. The outpatient group had nearly twice the diagnostic yield and management recommendations did not differ between the groups. Inclusion of genetic providers in the review of inpatient genetic testing requests should be considered to improve outcomes.
Journals
2026 EN
Katz Kylie · Jensik Philip · Velinov Milen
ABSTRACT DEAF1 ‐associated neurodevelopmental disorder (DAND) is a neurodevelopmental spectrum disorder caused by two methods of inheritance: the autosomal dominant intellectual disability syndrome (Vulto‐van Silfout‐de Vries syndrome (VSVS), OMIM #615828), and the autosomal recessive Neurodevelopmental disorder with hypotonia and impaired expressive language with or without seizures (NEDHELS OMIM #615828) (OMIM 617171). All reported cases of VSVS have occurred de novo . In this report, we describe the case of a 2‐year‐old male with a history of autism spectrum disorder and behavioral concerns who was identified to be heterozygous for the c.837C>G (p.C279W) pathogenic variant in DEAF1 . Functional assays demonstrate that the p.C279W variant alters DEAF1's transcriptional repression activity. This variant was also identified in his 26‐year‐old mother, who also has a history of autism and speech delay. To the best of our knowledge, this is the first reported case of the dominant form of DEAF1 ‐associated neurodevelopmental disorder inherited from an affected parent.
Journals
2026 EN
Alvarez Griselda · Huang Alden · Grody Wayne W.
+1 more
ABSTRACT Alström syndrome (AS) is a rare autosomal‐recessive ciliopathy caused by biallelic variants in ALMS1 , with an incidence of 1 in 10,000 to 1 in 1,000,000 live births. We report a female diagnosed at age 5 with a previously unreported homozygous nonsense variant in ALMS1 : c.4740C>G (p.Tyr1580Ter), located in exon 8, a known hotspot for pathogenic variants. The variant aligns with the loss‐of‐function mechanism seen in most ALMS1 ‐related AS cases and is found within a 15 Mb run of homozygosity, consistent with her history of parental consanguinity. Her clinical picture included progressive hearing loss, dyslipidemia, and worsening hyperglycemia despite lifestyle interventions. Due to accelerated weight gain and declining glycemic control, dulaglutide, a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA), was initiated. Over 48 weeks, BMI decreased from 190% to 160% of the 95th percentile, with a 0.95 z ‐score reduction, 1.2% HbA1c decrease into the normal range. This case expands our understanding of the ALMS1 mutational spectrum and provides the first longitudinal report of GLP‐1 RA benefit in AS, supporting its consideration as adjunctive therapy and highlighting the need for further study.
Journals
2026 EN
ArbaizaBayona Ana Lucia · Mundry Roger · Malaivijitd Suchinda
+3 more
ABSTRACT Maternal care is ubiquitous in mammals, yet its degree and duration vary across taxa. In primates, mothers provide extended care for young and follow similar developmental transitions in the mother–infant relationship, yet at different paces of change. Since ecological pressures shape life‐history traits including female reproductive rate and timing of infant independence, research is needed on mother–infant relationships in wild populations exposed to energetic constraints and predation risk. Assamese macaques ( Macaca assamensis ) of the study population are seasonal breeders living in an unpredictable environment, where fluctuating food availability imposes energetic challenges on mothers and infants. We quantitatively describe how maternal care and offspring independence develop throughout infancy. Using continuous focal observations on 59 infants, we model the nonlinear age‐trajectories of mother–infant proximity and transitions from dependent to independent feeding and locomotion, and estimated sex differences in these trajectories. Newborns were fully dependent on their mothers for feeding and transport, with mothers maintaining close proximity. A transitional phase emerged between 1 and 3 months of age, marked by reduced maternal proximity and increasing infant independence. During the second half of infancy, infants achieved near‐complete locomotor and feeding independence, while residual proximity and body contact persisted. No sex differences were detected in the mother–infant relationship trajectory. Collectively, the timing of maternal investment aligns with the breeding strategy of this seasonal species, with females balancing investment in current and future reproduction. This study establishes a baseline for examining how ecological variability affects the timing and pace of mother–infant behavioral transitions.
Journals
2026 EN
Portal Camille Gabriela Ramos · Imbeloni Aline Amaral · Rahal Sheila Canevese
+5 more
ABSTRACT Degenerative changes of the vertebral column are common in aging primates; however, patterns of spinal osteopathy remain poorly characterized across small‐ and medium‐bodied primate species, limiting comparative interpretations of skeletal aging. Expanding assessments beyond well‐studied taxa provides a broader framework for understanding primate musculoskeletal senescence and generates baseline data essential for interpreting vertebral degeneration in wild and semi‐free‐ranging populations, where ecological and life‐history factors influence skeletal aging. We investigated age‐, sex‐, and body mass–related variation in vertebral osteopathies radiographically assessed in 70 captive vervet monkeys ( Chlorocebus aethiops ). Osteophytes were the most frequent lesion (78.6%), followed by discopathy (12.7%), syndesmophytes (2.9%), and scoliosis (1.4%). Age was the primary predictor of osteophyte presence across spinal regions, whereas sex and body mass showed no significant independent effects. In contrast, total osteophyte scores were significantly higher in older, heavier individuals, and females exhibited slightly higher adjusted scores than males. Nonlinear regression models revealed distinct age‐related trajectories among spinal regions, with osteophytes emerging earliest in the lumbar spine (~ 1 year), followed by the cervical (~ 7 years) and thoracic (~ 9 years) regions. These findings characterize the natural history of spinal degeneration in vervet monkeys under captive conditions and provide comparative baseline data for distinguishing age‐related changes from pathological alterations in both captive and free‐ranging primate populations.
Journals
2026 EN
Langfield Cameron T. · Hanley Natalia · Payne Jason L.
+1 more
ABSTRACT While research has identified a disconnect between the minimum age of criminal responsibility (MACR) and public perceptions of criminal culpability among young people, no study has examined how offender characteristics influence support for reform using an experimental design. To address this, this study presents the first experimental test of public attitudes toward raising the MACR, offering a novel contribution to debates on youth justice reform in Australia and internationally. Drawing on data from 298 participants who completed a factorial survey experiment, this study varies offender age (10, 12, 14, or 16) and offending history (first‐time versus repeat) to explore support for limiting criminal justice responses to warnings or cautions among community members. A multivariate logistic regression indicated greater public support toward younger offenders (OR = 1.09), with support declining as age increased. Prior offending was associated with lower levels of support (OR = 0.07). Women and younger respondents showed the highest level of support (OR = 6.15), but their support declined more sharply as the offender aged. These findings provide insights into the conditional nature of public support for MACR reform and he need for experimental methodology to be utilised more widely when estimating support for youth justice‐related topics.