SOLAMEN syndrome is a rare, recently recognized congenital syndrome that is characterized by progressive and hypertrophic diseases involving multiple systems, including segmental overgrowth, lipomatosis, arteriovenous malformation (AVM) and epidermal nevus. According to literatures, SOLAMEN syndrome is caused by heterozygous PTEN mutation. Phenotypic overlap complicates the clinical identification of diseases associated with PTEN heterozygous mutations, making the diagnosis of SOLAMEN more challenging. In addition, SOLAMEN often presents with segmental tissue overgrowth and vascular malformations, increasing the possibility of misdiagnosis as klipple-trenaunay syndrome or Parks-Weber syndrome. Here, we present a case of a child presenting with macrocephaly, patchy lymphatic malformation on the right chest, marked subcutaneous varicosities and capillaries involving the whole body, overgrowth of the left lower limb, a liner epidermal nevus on the middle of the right lower limb, and a large AVM on the right cranial thoracic entrance. Based on the typical phenotypes, the child was diagnosed as SOLAMEN syndrome. detailed clinical, imaging and genetic diagnoses of SOLAMEN syndrome was rendered. Next-generation sequencing (NGS) data revealed that except for a germline PTEN mutation, a PDGFRB variant was also identified. A subsequent echocardiographic examination detected potential cardiac defects. We suggested that given the progressive nature of AVM and the potential severity of cardiac damage, regular echocardiographic evaluation, imaging follow-up and appropriate interventional therapy for AVM are recommended.

BACKGROUND: Situs inversus totalis is a rare malposition of organs that typically involves lesions in the respiratory, circulatory, or urinary systems. Cases of congenital hemivertebrae combined with situs inversus totalis are extremely rare and have limited reports.
METHODS: We report a 2.5 years old girl with 2 congenital hemipyramids and complete visceral inversion who ultimately underwent hemilaminectomy.
METHODS: Congenital hemivertebrae combined with situs inversus totalis.
METHODS: The patient underwent hemilaminectomy.
RESULTS: The spinal deformity was corrected.
CONCLUSIONS: For patient with spinal deformities combined with situs inversus totalis, surgery can be an effective treatment method. But we also need to be vigilant about the dysfunction of various systems.

BACKGROUND: Hemifacial macrosomia (HFM, OMIM 164210) is a complex and highly heterogeneous disease. FORKHEAD BOX I3 (FOXI3) is a susceptibility gene for HFM, and mice with loss of function of Foxi3 did exhibit a phenotype similar to craniofacial dysmorphism. However, the specific pathogenesis of HFM caused by FOXI3 deficiency remains unclear till now.
METHODS: In this study, we first constructed a Foxi3 deficiency (Foxi3-/- ) mouse model to verify the craniofacial phenotype of Foxi3-/- mice, and then used RNAseq data for gene differential expression analysis to screen candidate pathogenic genes, and conducted gene expression verification analysis using quantitative real-time PCR.
RESULTS: By observing the phenotype of Foxi3-/- mice, we found that craniofacial dysmorphism was present. The results of comprehensive bioinformatics analysis suggested that the craniofacial dysmorphism caused by Foxi3 deficiency may be involved in the PI3K-Akt signaling pathway. Quantitative real-time PCR results showed that the expression of PI3K-Akt signaling pathway-related gene Akt2 was significantly increased in Foxi3-/- mice.
CONCLUSIONS: The craniofacial dysmorphism caused by the deficiency of Foxi3 may be related to the expression of Akt2 and PI3K-Akt signaling pathway. This study laid a foundation for understanding the function of FOXI3 and the pathogenesis and treatment of related craniofacial dysmorphism caused by FOXI3 dysfunction.

BACKGROUND: TNRC6B deficiency syndrome, also known as global developmental delay with speech and behavioral abnormalities (MIM 619243), is a rare autosomal dominant genetic disease mainly characterized by facial dysmorphism, developmental delay/intellectual disability (DD/ID), speech and language delay, fine and motor delay, attention deficit and hyperactivity disorder (ADHD), and variable behavioral abnormalities. It is caused by heterozygous variant in the TNRC6B gene (NM_001162501.2, MIM 610740), which encodes the trinucleotide repeat-containing adaptor 6B protein.
METHODS: In this study, two Chinese patients with TNRC6B deficiency syndrome were recruited, and genomic DNA extraction from peripheral blood leukocytes of these parents and their family members was extracted for whole-exome sequencing and Sanger sequencing.
RESULTS: Here, we report two unrelated Chinese patients diagnosed with TNRC6B deficiency syndrome caused by novel de novo likely pathogenic or pathogenic TNRC6B variants c.335C>T (p.Pro112Leu) and c.1632delC (p.Leu546fs*63), which expands the genetic spectrum of TNRC6B deficiency syndrome. The clinical features of the patients were DD/ID, delayed speech, ADHD, behavioral abnormalities, short stature, low body weight, café-au-lait spots, metabolic abnormalities, and facial dysmorphism including coarse facial features, sparse hair, frontal bossing, hypertelorism, amblyopia, strabismus, and downslanted palpebral fissures, which expands the phenotype spectrum associated with TNRC6B deficiency syndrome.
CONCLUSIONS: This study expands the genotypic and phenotypic spectrum of TNRC6B deficiency syndrome. Our findings indicate that patients with TNRC6B deficiency syndrome should be monitored for growth and metabolic problems and therapeutic strategies should be developed to address these problems. Our report also suggests the clinical diversity of TNRC6B deficiency syndrome.

Congenital vertebral malformation, affecting 0.13-0.50 per 1000 live births, has an immense locus heterogeneity and complex genetic architecture. In this study, we analyze exome/genome sequencing data from 873 probands with congenital vertebral malformation and 3794 control individuals. Clinical interpretation identifies Mendelian etiologies in 12.0% of the probands and reveals a muscle-related disease mechanism. Gene-based burden test of ultra-rare variants identifies risk genes with large effect sizes (ITPR2, TBX6, TPO, H6PD, and SEC24B). To further investigate the biological relevance of the genetic association signals, we perform single-nucleus RNAseq on human embryonic spines. The burden test signals are enriched in the notochord at early developmental stages and myoblast/myocytes at late stages, highlighting their critical roles in the developing spine. Our work provides insights into the developmental biology of the human spine and the pathogenesis of spine malformation.

OBJECTIVE: The natural history of congenital scoliosis (CS) caused by hemivertebra varies greatly. This study aimed to explore the association between the morphology of hemivertebra and the severity of CS, since the diagnosis of the hemivertebra.
METHODS: Patients with isolated (single fully segmented) hemivertebra were enrolled. The degree and progression of deformity were compared by three morphological parameters of hemivertebra, comprising whether the width of hemivertebra extends across the central vertical line of lower adjacent vertebra (midline); the lateral height ratio (LHR, lateral height of hemivertebra× 2/(lateral height of HV-1 plus HV + 1) with the cut-point being 0.9; and the sagittal position of hemivertebra that was divided into the lateral and posterolateral group.
RESULTS: In total, 156 patients (mean age 9.7 ± 6.2 years, 81 males) were enrolled. The number of thoracic, thoracolumbar (T12/13-L1), and lumbar hemivertebrae were 63, 41, and 52, respectively. Hemivertebrae across the midline had larger scoliosis and kyphosis (58.3 ± 20.6° vs. 42.8 ± 15.0°, P <  0.001; 45.1 ± 32.5° vs. 29.5 ± 25.7°, P = 0.013, respectively). Hemivertebrae with LHR ≥0.9 was associated with larger scoliosis (55.7 ± 20.6° vs. 41.4 ± 13.3°, P <  0.001). Larger scoliosis and kyphosis were observed in posterolateral hemivertebrae (54.4 ± 21.0° vs. 44.4 ± 15.6°, P = 0.026; 51.4 ± 31.5° vs. 20.6 ± 17.1°, P <  0.001, respectively). Co-occurrence of more than one of the three positive parameters above indicated higher annual progression (5.0 ± 2.2° vs. 3.3 ± 1.3°, P <  0.001).
CONCLUSIONS: Three positive parameters, width across the midline, LHR ≥0.9, and posterolateral position were associated with a more severe deformity in patients with isolated hemivertebra. Hemivertebrae with more than one positive parameter may cause progressive deformity, and thus need prompt surgery.
METHODS: Prognostic, level IV.

This paper introduces a solution to address the intricacy of the model employed in the deep learning-based diagnosis of musculoskeletal abnormalities and the limitations observed in the performance of a single deep learning network model. The proposed approach involves the integration of an improved EfficientNet-B2 model with MobileNetV2, resulting in the creation of FusionNet. First, EfficientNet-B2 is combined with coordinate attention (CA) to obtain CA-EfficientNet-B2. Furthermore, aiming to minimize the model parameter count, we further enhanced the mobile inverted residual bottleneck convolution module (MBConv) employed for feature extraction in EfficientNet-B2, resulting in the development of CA-MBC-EfficientNet-B2. Next, the features extracted from CA-MBC-EfficientNet-B2 and MobileNetV2 are fused. Finally, the final diagnosis of musculoskeletal abnormalities was performed by using fully connected layers. The experimental results demonstrate that, first, compared to EfficientNet-B2, CA-MBC-EfficientNet-B2 not only significantly improves the diagnostic performance of musculoskeletal abnormalities, it also reduces the parameter count and storage space by 17%. Moreover, as compared to other models, FusionNet demonstrates remarkable performance in the area of anomaly diagnosis, particularly on the elbow dataset, achieving a precision of 92.93%, an AUC of 93.89% and an accuracy of 87.10%.

BACKGROUND: Immune skeletal dysplasia with neurodevelopmental abnormalities (ISDNA) is an extremely rare, autosomal recessive genetic disorder characterized by various skeletal abnormalities, neurodevelopmental deficits, and abnormal immune system function. ISDNA is caused by variation in the exostosin-like 3 (EXTL3) gene, located on chromosome 8p21.2, whose primary function is the biosynthesis of heparan sulfate (HS) skeleton structure. Only a few variations in the EXTL3 gene have been discovered so far. In these years of development, many pathogenic variants in genetic diseases with genetic and phenotypic heterogeneity have been investigated using whole-exome sequencing (WES) technology.
METHODS: In this research, a novel EXTL3 variant was first detected in a patient using WES, which was validated from Sanger sequencing in this family. Family history and clinical information were then collected through comprehensive medical examinations and genetic counseling. In silico prediction was then utilized to confirm the pathogenicity of the variant.
RESULTS: A novel homozygous variant, NM_001440: c.2015G>A (p.Arg672Gln) in the EXTL3 gene, was identified using WES, which has never been reported before. Sanger sequencing was performed to confirm that the variant segregated with the disease within the family.
CONCLUSIONS: This research identified a novel pathogenic variant in the EXTL3 gene responsible for ISDNA in a Chinese family. It showed the potential diagnostic role of WES in ISDNA, expanded the EXTL3 gene variation spectrum, and demonstrated that the diagnosis of ISDNA using WES is feasible and effective. More comprehensive genetic counseling and precise prenatal diagnosis for the next pregnancy can also be provided to families with genetic disorders.

OBJECTIVE: Although the Roussouly classification has been widely used in surgical planning for adult scoliosis patients, little is known about whether it can be used to guide sagittal correction for adolescent idiopathic scoliosis (AIS) patients. The purpose of this study was to explore whether the Roussouly classification could be used to help surgeons restore the ideal sagittal alignment for AIS patients to avoid the development of proximal junctional kyphosis (PJK).
METHODS: In this retrospective cohort study, eighty-seven patients with Lenke 5 AIS who underwent surgery from January 2010 to August 2020 were enrolled and divided into two groups: the PJK group and the non-PJK group. All patients were classified into \"current types\" and \"ideal types\" according to two versions of the Roussouly classification, and the mismatch rate was evaluated in terms of the consistency between their current type and ideal type. Student\'s t test, Mann‒Whitney U test, Pearson\'s Chi-square test, and others were used to compare the two groups regarding patient demographic characteristics (age, sex, Risser sign, etc.) and radiographic parameters (sagittal vertical axis [SVA]; thoracic kyphosis [TK]; thoracolumbar junctional kyphosis [TLK]; lumbar lordosis [LL]; pelvic incidence [PI]; pelvic tilt [PT]; sacral slope [SS]; upper instrumented vertebra [UIV]; lower instrumented vertebra [LIV]; etc.). Multivariate logistic regression with backwards stepwise selection was performed to identify the risk factors for PJK.
RESULTS: PJK was observed in 16 out of 87 patients (18.4%) until the final follow-up. The incidence of PJK was significantly higher in the patients not matching their ideal type than in those who did after surgery (60.9% vs. 3.1%, p = 0.000). The patients with ideal Type 1 had the highest incidence of PJK, while the lowest incidence was observed in patients with ideal Type 2 (50.0% vs. 5.1%, p = 0.000). The PJK group had greater TK, LL, and PI-LL than the non-PJK group before and after surgery. The postoperative PJA in the PJK group was also larger than that in the non-PJK group. Multivariate logistic regression revealed that postoperative Roussouly type mismatch was significantly associated with the occurrence of PJK (OR = 64.2, CI = 9.6-407.1, p = 0.000).
CONCLUSIONS: The Roussouly classification could serve as a prognostic tool for PJK in Lenke 5 AIS patients. Corrective surgery should restore sagittal alignment with respect to the patient\'s ideal sagittal profile (according to the Roussouly classification based on the PI) to decrease the incidence of PJK in AIS patients.

Congenital muscular hypertrophy is a rare overgrowth disorder in the phosphatidylinositol-3-kinase related spectrum. In the past 3 years, ten patients with 11 limbs involved were treated in our centre. The aim of the study was to describe the clinical and radiological deformities of these patients. We documented the characteristic clinical morphological changes, such as hypertrophy, loss of wrist flexion, thumb hyperabduction, finger deviation and skin crease changes in the palm. Radiologically, the mean first metacarpal radial deviation angle of the affected side measured 55° (range 34 to 67) compared to the normal contralateral side 42° (range 32 to 53). The mean intermetacarpal space ratio was 1.2 (range 1.1 to 1.4) and the mean palm width ratio was 1.2 (range 1.1 to 1.3). In this study, we were able to further characterize the radiological and morphological changes of congenital muscular hypertrophy of upper limbs, which would be helpful for establishing the diagnosis and monitor treatment of this rare condition.Level of evidence: IV.