SATB2-associated syndrome (SAS) results from various mutations of the SATB2 gene and associates a neurodevelopmental disorder including major speech delay, intellectual disability, and behavioral problems with dental anomalies, sometimes a cleft palate, risk of osteoporosis, and facial dysmorphism. The principal objective of this study was to describe the oral phenotype of young children with SATB2-associated syndrome, especially in terms of orofacial malformation of Robin Sequence (RS) spectrum (bifid uvula, cleft palate, or RS, dental malformation, feeding and communication, with data from a national cohort. The secondary objective was to determine whether feeding and communication disorders were more severe when associated with an orofacial malformation of RS spectrum. We conducted a retrospective cross-sectional study among the largest possible cohort of patients with a mutation of the SATB2 gene in France. A questionnaire completed by the referring physicians and by telephone with parents enabled us to collect the following clinical information: (1) orofacial morphology, feeding difficulties, and pharyngeal functioning from birth to 3 years, (2) communication and language from 0 to 6 years, (3) speech development at the last examination. The study included 40 patients. Early and persistent feeding difficulties were found in 55% of the children. Communication was abnormal from the first months of life, with poor babbling in 85% of them. A major language delay was described in all patients; 65% had a vocabulary of 10 words or less. An anomaly of RS spectrum was found in half the cases, and dental malformations were described in 90%. Feeding difficulties and language delay were greater in the group with one or more orofacial malformations than the group with none. This study confirmed the severity of oral involvement, affecting feeding and speech simultaneously, in individuals with SAS. It raises the question of why the oral phenotype involving feeding and speech is more severe in the presence of cleft palate or RS. We recommend close monitoring of prelanguage communication in infants with apparently isolated cleft palate or RS and the search for SATB2 impairment when a cleft palate or RS is found, especially in the prenatal period.

The current development of gynecology services for children and adolescents seeks to meet needs both in the overall population and in patients with rare diseases. In France, the referral center for rare gynecological diseases specializes in four major types of conditions, namely, uterovaginal malformations, hereditary hemorrhagic diseases, rare benign breast diseases, and gynecological repercussions of rare chronic diseases. To describe consecutive patients who had a first visit in 2018-2023 at the referral center for rare gynecological diseases at the Necker Pediatric University Hospital in Paris, France, and who were diagnosed with a condition in any of the four categories listed above. For this single-center retrospective observational cohort study, data from the referral-center database were collected and reviewed. These data included year of birth, age at and reason for first gynecology visit, and rare chronic disease and referring rare-disease center for patients seen for gynecological repercussions of rare chronic diseases. The 704 included patients had a median age of 15.2 years (interquartile range 3.8) at the first visit. Among them, 100 (14.2%) had uterovaginal malformations, 32 (4.6%) hereditary hemorrhagic diseases, 17 (2.4%) rare benign breast diseases, and 555 (78.8%) gynecological repercussions of rare chronic diseases. The leading reasons for the visit were dysmenorrhea (15.6%), menorrhagia (15.5%), uterovaginal malformations (15.2%), and irregular periods (14.9%). Repercussions of rare chronic diseases managed at rare-disease referral centers were by far the leading reason for seeking gynecological expertise in rare diseases. In this complex situation, the underlying disease and its treatments interact with the gynecological manifestations and their treatment, requiring close collaboration among all specialists caring for each patient.

Fetal alcohol spectrum disorder (FASD) is the leading cause of non-genetic intellectual disabilities. Many healthcare professionals in France have benefited from initial and continuing training programs on this public health theme. The objective of our study is to describe and compare knowledge of FASD among health professionals in two different french regions with a health prevention and information system (Indian Ocean (IO)) or without (Nouvelle-Aquitaine (NA)). A free and anonymous electronic survey related to perinatality, childhood and adolescence was sent by email or social networks to various health professionals in the IO and NA regions. Responses were analyzed by comparing the function and affiliation of healthcare professionals to each region. We obtained 193 replies from the IO and 265 replies from NA. On the one hand, 79 % of healthcare professionals reported receiving training on FASD, and most of them were aware that there is no threshold of maternal alcohol intake without risk to the fetus. It appears that 91 % of them are aware of the cognitive-behavioral disorders associated with the diagnosis of FASD. On the other hand, barely 19 % were aware that maternal age is a risk factor, and only 39 % had knowledge of the three cardinal signs of FAS dysmorphia. Only 30 % described a neurological anomaly related to the diagnosis. Regarding alcohol-related neurodevelopmental disorders, 30 % wrongly believed that growth retardation and facial dysmorphia were necessary for diagnosis. Data analysis reveals more variability in inter-professional knowledge in the region without a platform. While there is no direct significant difference between regions regarding knowledge of the FASD, among the NA respondents, only 32 % reported that paternal alcohol consumption was a risk factor, whereas 51 % of the IO respondents were already aware of it. This study points out the heterogeneity of healthcare professionals' knowledge of FASD within each region. It highlights the challenge of informing, training and orienting mothers and their children in an appropriate manner. The establishment of diagnostic platforms seems essential to provide early, optimised and adapted care in response to this particular public health problem.

Describe the intelligence quotient (IQ) of children with Pierre Robin sequence (PRS). Prospective cohort study. Neurodevelopmental follow-up clinic within a hospital. Children with PRS (n = 45) who had been in the Neonatal Intensive Care Unit (NICU) were classified by a geneticist into 3 subgroups of isolated PRS (n = 20), PRS-plus additional medical features (n = 8), and syndromic PRS (n = 17) based on medical record review and genetic testing. Children with PRS completed IQ testing at 5 or 8 years of age with the Wechsler Preschool and Primary Scale of Intelligence, Third Edition (WPPSI-III) or Fourth Edition (WPPSI-IV) or the Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) or Fifth Edition (WISC-V). IQ scores were more than 1 to 2 standard deviations below the mean for 36% of the overall sample, which was significantly greater compared to test norms (binomial test P = .001). There was a significant association between PRS subtype and IQ (Fisher's exact P = .026). While only 20% of children with isolated PRS were within 1 standard deviation below average and 35% of children with syndromic PRS were below 1 to 2 standard deviations, 75% of PRS-plus children scored lower than 1 to 2 standard deviations below the mean. PRS subgroups can help identify children at risk for cognitive delay. The majority of children with PRS-plus had low intellectual functioning, in contrast to the third of children with syndromic PRS who had low IQ and the majority of children with isolated PRS who had average or higher IQ.

Epcoritamab is a subcutaneously administered CD3xCD20 T-cell-engaging, bispecific antibody that activates T cells, directing them to kill malignant CD20+ B cells. Single-agent epcoritamab previously demonstrated potent antitumor activity in dose escalation across B-cell non-Hodgkin lymphoma subtypes. In the dose-expansion cohort of a phase I/II study (ClinicalTrials.gov identifier: NCT03625037), adults with relapsed or refractory CD20+ large B-cell lymphoma and at least two prior therapy lines (including anti-CD20 therapies) received subcutaneous epcoritamab in 28-day cycles (once weekly step-up doses in weeks 1-3 of cycle 1, then full doses once weekly through cycle 3, once every 2 weeks in cycles 4-9, and once every 4 weeks in cycle 10 and thereafter) until disease progression or unacceptable toxicity. The primary end point was overall response rate by the independent review committee. As of January 31, 2022, 157 patients were treated (median age, 64 years [range, 20-83]; median of three [range, 2-11] prior therapy lines; primary refractory disease: 61.1%; prior chimeric antigen receptor (CAR) T-cell exposure: 38.9%). At a median follow-up of 10.7 months, the overall response rate was 63.1% (95% CI, 55.0 to 70.6) and the complete response rate was 38.9% (95% CI, 31.2 to 46.9). The median duration of response was 12.0 months (among complete responders: not reached). Overall and complete response rates were similar across key prespecified subgroups. The most common treatment-emergent adverse events were cytokine release syndrome (49.7%; grade 1 or 2: 47.1%; grade 3: 2.5%), pyrexia (23.6%), and fatigue (22.9%). Immune effector cell-associated neurotoxicity syndrome occurred in 6.4% of patients with one fatal event. Subcutaneous epcoritamab resulted in deep and durable responses and manageable safety in highly refractory patients with large B-cell lymphoma, including those with prior CAR T-cell exposure. ANKRD17-related neurodevelopmental syndrome is characterized by developmental delay – particularly affecting speech – and variable intellectual disability. Additional features include autism spectrum disorder, attention-deficit/hyperactivity disorder, ophthalmologic abnormalities (strabismus and refractive errors), growth deficiency, feeding difficulties, recurrent infections, gait and/or balance disturbances, and epilepsy. Characteristic craniofacial features include triangular face shape, high anterior hairline, deep-set and/or almond-shaped eyes with periorbital fullness, low-set ears, thick nasal alae and flared nostrils, full cheeks, and thin vermilion of the upper lip. Less common but distinctive features include cleft palate with Pierre Robin sequence, renal agenesis, and scoliosis. The diagnosis of ANKRD17-related neurodevelopmental syndrome is established in a proband with a heterozygous pathogenic variant in ANKRD17 identified by molecular genetic testing. Treatment of manifestations: Developmental and educational support; standard treatments for seizures, behavioral findings, ophthalmologic involvement, genitourinary anomalies, and spasticity; feeding therapy with gastrostomy tube placement as needed for persistent feeding issues; routine immunizations; referral to immunologist for those with recurrent infections; family support and care coordination as needed. Surveillance: Assess developmental progress, educational needs, seizures, changes in tone, movement disorders, growth, nutrition, feeding, and family needs at each visit; assess behavioral and musculoskeletal manifestations annually or as needed. Pregnancy management: The teratogenic risk to the fetus associated with the use of anti-seizure medication during pregnancy depends on the type of anti-seizure medication used, the dose, and the gestational age of the fetus. ANKRD17-related neurodevelopmental syndrome is an autosomal dominant disorder typically caused by a de novo pathogenic variant. If the ANKRD17 pathogenic variant identified in the proband is not identified in either parent, the risk to sibs is low but greater than that of the general population because of the possibility of parental germline mosaicism. Once the ANKRD17 pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.