Stüve-Wiedemann Syndrome is a rare genetic condition identified in a limited number of patients, transmitted in an autosomal recessive manner and characterized by neuro-myo-skeletal deformities. Affected newborns frequently do not survive beyond one year due to life-threatening complications. Dental practitioners should be aware of this syndrome and its oral and maxillofacial manifestations to ensure accurate diagnosis, prevent treatment-related complications, and achieve effective treatment planning. Today, early identification and appropriate genetic testing contribute to a marked increase in the lifespan of survivors.

Stuve-Wiedemann Syndrome (SWS) is a rare autosomal recessive condition, first reported in 1971 by Stuve and Wiedemann. It is associated with pathogenic or likely pathogenic homozygous or compound heterozygous variants in the Leukemia Inhibitory Factor Receptor (LIFR) gene. The condition is characterized by skeletal abnormalities, including bowed long bones and joint contractures, as well as severe dysautonomia due to defects in the ciliary neurotrophic factor receptor pathway, which leads to life-threatening complications such as hyperthermia, respiratory distress, and feeding difficulties, resulting in a high early mortality rate. We report a 5-month-old girl with dysmorphic features, hypotonia, bent long bones, bouts of hyperthermia, and failure to thrive. DNA analysis showed a homozygous pathogenic variant in the LIFR gene consistent with Stuve-Wiedemann Syndrome (SWS). SWS is a rare autosomal recessive disorder characterized by autonomic dysfunction and bent-bone dysplasia due to pathogenic homozygous or compound heterozygous variants in the LIFR gene. Management is currently supportive, and further research is required to improve treatment and prognosis.

Stüve-Wiedemann syndrome (SWS) is a rare autosomal recessive genetic disorder characterised by skeletal dysplasia, dysautonomia, and multi-system abnormalities. It is typically caused by variants in the leukaemia inhibitory factor receptor (LIFR) gene. This case report presents a novel and complex heterozygous variant in the LIFR gene in a 2-month-old Chinese infant, which contributes to the limited literature on SWS in the Chinese population and underscores the importance of early identification and intervention. The infant was born at 38 weeks of gestation via caesarean section due to breech presentation. He presented with multiple symptoms, including persistent pulmonary hypertension of the newborn, recurrent hyperthermia, and joint deformities. Whole exome sequencing identified a novel compound heterozygous variant in the LIFR gene. The infant underwent various interventions, including mechanical ventilation, inhaled nitric oxide, and nasogastric feeding. Despite these measures, the infant experienced recurrent hyperthermia episodes leading to multi-organ dysfunction. The infant was eventually stabilised, but follow-up revealed global developmental delay and persistent skeletal abnormalities. Early identification of the LIFR gene variant is crucial for timely intervention and management of multi-system complications. Further research is warranted to explore targeted therapies and improve outcomes for patients with this rare disorder.

Stüve-Wiedemann syndrome is a rare skeletal dysplasia characterized by severe shortening and bowing of the long bones and by immunological and autonomous dysfunction, usually resulting in early death. Bi-allelic loss-of-function variants in either the leukemia inhibitory factor receptor encoding LIFR or the interleukin-6 cytokine family signal transducer encoding IL6ST are causative. So far, five individuals from three unrelated families were described with IL6ST associated Stüve-Wiedemann syndrome. We here report on a sixth case that came to attention at 21 weeks of gestation with short and bowed long bones. Prenatal trio exome sequencing revealed the homozygous novel variant p.(Ser375∗) in IL6ST in the fetus. The further course of the pregnancy was complicated by early rupture of the membranes and preeclampsia. The fetus died in utero in gestational week 34 and was born with dolichocephalus, severe bowing and shortening of limb bones, a narrow upper thorax, joint dislocations and abnormal bone mineralization. With this case report, we further delineate the molecular and clinical spectrum of IL6ST related Stüve-Wiedemann syndrome.

Stuve-Wiedemann syndrome (SWS) is a rare skeletal abnormality with extensive postnatal literature but limited prenatal studies. Our group had published a diagnostic algorithm to identify prenatal cases, yet, the challenge continues, especially when there is no family history of a similar condition. We retrospectively analyzed our experience of prenatal diagnosis of SWS over an 8-year period with ethical approval. Literature review of articles published until July 30, 2023 from PubMed, GeneReviews, and Genetics Home Reference using search parameters, "SWS," "prenatal," and "ultrasound" was conducted. Three cases (diagnosed during the routine anomaly scan) were identified from our institutional review, and 11 cases from six studies from the literature review. Eight out of these 11 cases had a positive family history. SWS was recognized without positive family history in two patients from literature review and the three patients in the current study. The consistent findings that helped in reaching the suspicion were the typical pattern of long bone involvement (bowing of tibia > femora, relative sparing of the fibula and upper limb bones, normal scapulae, and clavicles), and the presence of camptodactyly. Despite the lack of sonographic evidence of narrow thorax, SWS is highly lethal, due to dysautonomic symptoms. In SWS, accurate ultrasound diagnosis is crucial to provide prognostic information as the lethality does not depend on pulmonary hypoplasia. Examination of the hands looking for camptodactyly is crucial in skeletal dysplasias to distinguish SWS from other bent bone osteochondrodysplasias, namely, campomelic and kyphomelic dysplasias. This prenatal distinction has important implications for prognosis.