Watson syndrome is a rare genetic condition partly characterised by developmental delays and learning difficulties. A profile of speech and language skills associated with this developmental syndrome is yet to be described in the literature. In order to address this gap, this study presents the case of an 18-year-old man with Watson syndrome and reports both standardised and naturalistic assessments of speech, language, oro-motor skills, and semantic and phonemic fluency. Analyses included norm-referencing, discrepancy comparison, phonological process analysis, and acoustic analyses of voice and conversational fluency. The participant's semantic fluency approximated to the 84th percentile and the vocabulary, voice, and receptive language measures were within standard normative range. In contrast, expressive language difficulties and articulatory difficulties associated with impaired oro-motor skills were apparent. Specific tongue-motor difficulty impeded oral diadochokinesis, with gliding, stopping, and cluster reduction among the phonological processes observed to mitigate oro-motor difficulties. Language scores were lowest on tasks of working memory, syntax, and pragmatics, however neither syntax nor pragmatics presented increased difficulty in naturalistic conversation, indicating an influence of reduced working memory on language performance. The absence of explicit cognitive or communicative difficulty suggests specific speech and language difficulties. To conclude, the findings are discussed from both clinical and theoretical perspectives. Watson syndrome and the aetiology of communication difficulties are suggested as directions for future research, to validate these findings and diversify understanding of inclusive communication approaches.

Watson for the first time reported a case series of children in a family that presented with pulmonary valve stenosis, mental retardation, short stature, and small brown color skin lesions that are known as cafe-au-lait spots. We present a rare new variant of the syndrome in an adult patient with severe pulmonary valve stenosis, main, left, and right pulmonary artery aneurysm, short stature, mental retardation, coronary artery disease, and skin lesions. The patient underwent open cardiac surgery with pulmonary valvotomy and aneurysmorrhaphy of the main pulmonary artery and its right and left branches. The postoperative course was uneventful and the six-month follow-up with transthoracic echocardiography revealed no recurrence of aneurysm of repairing pulmonary arteries and good clinical outcome of the patient. Our patient had a unique characteristic of aneurysm of the main pulmonary artery and its both branches that has rarely been reported previously in the medical literature.

RASopathies are a group of disorders caused by disruptions to the RAS-MAPK pathway. Despite being in the same pathway, Neurofibromatosis Type 1 (NF1) and Legius syndrome (LS) typically present with phenotypes distinct from Noonan spectrum disorders (NSDs). However, some NF1/LS individuals also exhibit NSD phenotypes, often referred to as Neurofibromatosis-Noonan syndrome (NFNS), and may be mistakenly evaluated for NSDs, delaying diagnosis, and affecting patient management. A derivation cohort of 28 patients with a prior negative NSD panel and either NFNS or a suspicion of NSD and café-au-lait spots underwent NF1 and SPRED1 sequencing. To further determine the utility and burden of adding these genes, a validation cohort of 505 patients with a suspected RASopathy were tested on a 14-gene RASopathy-associated panel. In the derivation cohort, six (21%) patients had disease-causing NF1 or SPRED1 variants. In the validation cohort, 11 (2%) patients had disease-causing variants and 15 (3%) had variants of uncertain significance in NF1 or SPRED1. Of those with disease-causing variants, 5/17 only had an NSD diagnosis. Adding NF1 and SPRED1 to RASopathy panels can speed diagnosis and improve patient management, without significantly increasing the burden of inconclusive results.

Neurofibromin 1 (NF1) is a tumor suppressor gene encoding a Ras GTPase that negatively regulates Ras signaling pathways. Mutations in NF1 are linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. In terms of antitumor immunity, CD1d-dependent natural killer T (NKT) cells play an important role in the innate antitumor immune response. Generally, Type-I NKT cells protect (and Type-II NKT cells impair) host antitumor immunity. We have previously shown that CD1d-mediated antigen presentation to NKT cells is regulated by cell signaling pathways. To study whether a haploinsufficiency in NF1 would affect CD1d-dependent activation of NKT cells, we analyzed the NKT-cell population as well as the functional expression of CD1d in Nf1+/- mice. Nf1+/- mice were found to have similar levels of NKT cells as wildtype (WT) littermates. Interestingly, however, reduced CD1d expression was observed in Nf1+/- mice compared with their WT littermates. When inoculated with a T-cell lymphoma in vivo, Nf1+/- mice survived longer than their WT littermates. Furthermore, blocking CD1d in vivo significantly enhanced antitumor activity in WT, but not in Nf1+/- mice. In contrast, a deficiency in Type-I NKT cells increased antitumor activity in Nf1+/- mice, but not in WT littermates. Therefore, these data suggest that normal NF1 expression impairs CD1d-mediated NKT-cell activation and antitumor activity against a T-cell lymphoma.

The KCL025 human embryonic stem cell line was derived from an embryo donated for research that carried an autosomal dominant mutation in the NF1 gene encoding neurofibromin (c.3739-3742 ΔTTTG). Mutations in this gene have been linked to neurofibromatosis type 1, juvenile myelomonocytic leukemia and Watson syndrome. The ICM was isolated using laser microsurgery and plated on γ-irradiated human foreskin fibroblasts. Both the derivation and cell line propagation were performed in an animal product-free environment. Pluripotent state and differentiation potential were confirmed by in vitro assays.