Facial Abnormalities Research Articles

Perioperative Management in Rothmund–Thomson Syndrome

Rothmund-Thomson Syndrome (RTS) is a rare, multisystem disease accompanied by many anomalies that require careful attention from preoperative evaluation to discharge regarding anesthesia preparation and management. Due to craniofacial deformities accompanying facial abnormalities, maintaining the airway becomes a complete struggle with a race against time for survival. This case report presents the preoperative preparation and perioperative management, the risks that may be encountered, and the detailed preparation for a 7-year-old patient diagnosed with RTS and multiple system involvement. General anesthesia was administered to this patient, who had intrauterine growth retardation, nail streaking, redness of the bullae and legs, and a history of somatotropin treatment and antinuclear antibody (ANA) positivity under optimum conditions. Thanks to successful and detailed preoperative preparation and perioperative management, the patient was followed up and discharged without any complications. Although RTS is rare, the need for general anesthesia often arises due to juvenile cataracts, dental anomalies, syndactyly and other extremity anomalies in these patients whose airway management is complex. Furthermore, this increases the current risk in the population of these patients. Managing these patients with a multidisciplinary approach will reduce complications, morbidity, mortality, and length of stay.

The circadian clock component BMAL1 regulates osteogenesis in osseointegration.

Congenital and developmental craniofacial deformities often cause bone defects, misalignment, and soft tissue asymmetry, which can lead to facial function and morphologic abnormalities, especially among children born with cleft lip and palate. Joint efforts from oral maxillofacial surgery, oral implantology, and cosmetic surgery are often required for diagnosis and treatment. As one of the most widely performed treatment methods, implant-supported cranio-maxillofacial prostheses have been widely applied in the course of treatment. Therefore, stability of peri-implant bone tissue is crucial for the long-term success of treatment and patients' quality of life. The circadian clock component brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) was found to be involved in the cell fate of bone marrow mesenchymal stem cells, which were essential in the fixation of titanium implants. This study aimed to investigate the effect of BMAL1 on osteogenesis in osseointegration, providing a brand new solution to increase bone implant conjunction efficiency and implant stability, paving the way for a long-term satisfactory therapy outcome.

Case Report: Pentalogy of Cantrell with Cranioschisis and Facial Abnormality; An Extremely Rare Association

Case Report: Pentalogy of Cantrell with Cranioschisis and Facial Abnormality; An Extremely Rare Association

Facial and upper-limb movement abnormalities in individuals with psychotic-like experiences: a motion analysis study.

Slow movements and irregular muscle contraction have been reported separately in different studies targeting individuals with psychotic-like experiences (PLEs). To date, it remains unknown whether these two movement abnormalities, possibly associated with hypo- and hyper-dopaminergia, respectively, co-existed in one sample with PLEs and interrelated in the early stage of psychotic progression. Therefore, this study was to examine if facial and upper-limb slow movements and irregular muscle contraction co-existed in individuals with PLEs, interrelated, and were associated with PLEs. A total of 26 individuals with PLEs, who were identified using the 16-item Prodromal Questionnaire, and 26 age- and gender-matched healthy controls received the facial and upper-limb movement measurement. A motion capture system was used to record the movement procedure and thus calculate kinematic variables that represented severity of slow movements and irregular muscle contraction. Results showed that facial and upper-limb slow movements and facial irregular muscle contraction existed in individuals with PLEs. For the total sample, slower facial movements were associated with less regular facial muscle contraction; slower upper-limb movements were associated with less regular upper-limb muscle contraction. Slower and less regular facial and upper-limb movements were associated with more severe PLEs. Compensatory changes in dopaminergic neural pathways in response to elevated dopamine might explain connection between slow movements and irregular muscle contraction. Because of the ability to detect facial and upper-limb movement abnormalities objectively and sensitively, motion analysis has great applicability to sensorimotor studies for people in the psychosis continuum.

THROMBOCYTOPENIA, HYPOGAMMAGLOBULINEMIA, AND POOR VACCINE RESPONSE IN A PATIENT WITH TAKENOUCHI-KOSAKI SYNDROME

<h3>Introduction</h3> Takenouchi-Kosaki Syndrome (TKS) is a rare congenital developmental disorder characterized by thrombocytopenia, facial abnormalities, and varied multisystemic anomalies including immunodeficiency. Heterozygous deficiency of CDC42, an intracellular signaling GTPase, has been found in all TKS patients described to date. The immunological phenotypes of TKS patients are heterogeneous: recurrent infections have been noted in some patient series but with variable penetrance. Herein we describe a case of TKS causing hypogammaglobulinemia, B-cell lymphopenia, and poor vaccine response. <h3>Case Description</h3> A fifteen-year-old girl with history of developmental delay, multiple congenital defects, and lymphedema was referred to the immunology clinic for evaluation of recurrent ear infections that began at 3 months of age requiring tympanostomy tube placement at 18 months. Her physical exam was notable for abnormal facies, scoliosis, strabismus, abnormal thumbs, and unilateral lymphedema. Her laboratory evaluation revealed macrothrombocytopenia, mild leukopenia with low T-cells and markedly low B-cells by flow cytometry, and notably low IgA (11.7, RR 69 – 309) and IgG (423, RR 613 – 1295). She had a poor response to a full course of PCV7 with PPSV23 booster (9 of 23 > 1.3). Whole exome sequencing identified a heterozygous p.Y64C mutation in CDC42 consistent with TKS. <h3>Discussion</h3> The Y64C mutation in CDC42 is a TKS Group I lesion causing ineffective intracellular signaling, resulting in <i>in vitro</i> defects including abnormal cellular proliferation and disruption of cell polarity. Actin remodeling disorders such as Wiskott-Aldrich Syndrome and TKS should be considered in patients with immunodeficiency and congenital thrombocytopenia.

PMON193 Reactive oxygen species in the development of gonadal failure in late-onset transaldolase deficiency

Abstract Background Deficiency in Transaldolase, an essential enzyme in regulating NADPH and ribose 5-phosphate production, has been reported in only 39 patients to date. Most patients present already prenatally/neonatally with intra uterine growth retardation, hepato(spleno)megaly and consequent liver failure, anemia, thrombocytopenia, dysmorphic facial features, cardiac and skin abnormalities and hypergonadotropic hypogonadism in cases of late-onset presentation. The mechanism underlying gonadal dysfunction is not fully understood. Clinical case, methods and results A 15y old male from an Indian-Jewish background, with atrial-septal-defect, renal tubulopathy, mild facial dysmorphism and transient liver enzymes abnormalities presented with absence of pubertal development. His gonadotropins levels were elevated (LH – 22 IU/L, FSH 103 IU/L) while testosterone was low. Whole exome sequencing revealed homozygous variant in a novel T167M missense mutation in TALDO1 (transaldolase) gene whereas both parents were heterozygote carriers. Proteine structure analysis indicate that Threonine 167 is part of transaldolase catalytic site and critical for its function. As transaldolase activity is required for nucleic acids production, NADPH synthesis and reduction of cellular Reactive Oxygen Species (ROS) we measured the ROS accumulation using 2′,7′-dichlorodihydrofluorescein diacetate, in fibroblasts derived from the patient and normal controls. The affected patient's fibroblasts showed a significantly increased accumulation of ROS (207%, P=0.007), compared to controls indicating an increased susceptibility to oxidative stress. Conclusion The novel T167M missense mutation in the transaldolase (TALDO1) gene causes a unique clinical presentation including a relative mild liver involvement and hypergonadotrophic hypogonadism. The compromised TALDO1 activity in preventing cellular ROS accumulation in actual patient's fibroblasts is shown here for the first time and may indicate the therapeutic use of antioxidants in all patients with TALDO1 dysfunction. The high expression of TALDO1 in the testis and the gonadal failure suggests its tissue specific requirement in preventing the accumulation of ROS during steroidogenesis. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

SCIDISH – AN UNPREDICTED CASE OF T CELL LYMPHOPENIA, HYPOCALCEMIA, AND SKELETAL ANOMALIES

<h3>Introduction</h3> Biallelic pathogenic variants in <i>PAX1</i> lead to autosomal recessive otofaciocervical syndrome 2 (OTFCS2), characterized by facial and ear abnormalities, hearing loss, skeletal dysplasia, intellectual disability, branchial defects, and athymia. This rare case describes an infant who presented with T cell lymphopenia and hypocalcemia and was diagnosed with a novel homozygous PAX1 variant. <h3>Case Description</h3> A 6-day-old boy born to consanguineous parents was admitted for an abnormal newborn screen (TREC=0) and primary immunodeficiency with T-B+NK- immunophenotype (33/uL CD3+T-cells, 30/uL CD3/CD4/CD45RO cells, undetectable CD3/CD4/CD45RA cells, undetectable CD16/CD56NK-cells). Exam showed dysmorphic facial features, left preauricular pit, and sacral and should dimples. He received prophylactic antimicrobials, and immunoglobulin replacement for hypogammaglobulinemia. He developed seizures, attributed to hypocalcemia secondary to hypoparathyroidism. Further workup indicated presence of NK cells, absent thymic shadow, ASD and PFO on echocardiogram, failed hearing screen, mild laryngomalacia, kyphosis, and spinal subluxation of L5 on S1. FISH and microarray were negative for 22q11.2 deletion. Invitae Primary Immunodeficiency Panel revealed homozygous VUS (c.509C>A(p.Pro170His)) in PAX1, and parents are heterozygous carriers. Patient's clinical picture was most consistent with OTFCS2 with athymia. He was referred for thymus transplantation. <h3>Discussion</h3> Primary thymic defects should be considered in patients with abnormal SCID NBS, specifically in those with hypoparathyroidism. We suggest early genetic testing, as identification of the underlying defect is crucial for prognosis and management. As T-cell dysfunction in OTFCS2 is due to aberrant thymic development, allogeneic thymus transplantation is the expected curative treatment, whereas patients with PAX1 defects who underwent hematopoietic stem cell transplantation failed to gain T cell reconstitution.

A PATIENT WITH KABUKI SYNDROME AND HYPOGAMMAGLOBULINEMIA DEVELOPS BURKITT LYMPHOMA

<h3>Introduction</h3> Kabuki syndrome (KS) is a rare genetic disorder characterized by congenital abnormalities, autoimmunity, intellectual disability, distinctive facial abnormalities, and hypogammaglobulinemia. <h3>Case Description</h3> A 24-year-old male with KS and hypogammaglobulinemia presented to the emergency department (ED) with lower back pain and extremity paralysis. His previous genetic diagnosis of KS had a heterozygous novel variant causing a premature translational stop signal p.Pro235Alafs*6 in the KMT2D gene. The patient also has a history of congenital heart disease, autoimmune cytopenias, and longstanding hypogammaglobulinemia on/off replacement immunoglobulin with baseline IgG 300-400 mg/dL, low IgA 10-20 mg/dL, normal IgM 50-60 mg/dL, normal lymphocyte subsets, and absent protein and polysaccharide vaccine responses consistent with common variable immunodeficiency. On arrival at the ED, spinal imaging revealed a compression fracture and underlying mass. Right-axillary and bone marrow biopsies confirmed Burkitt lymphoma. He was treated with chemotherapy, radiation, and replacement immunoglobulin. He has suffered from pneumonia, adenovirus, ileus<b>,</b> heart failure, and stroke. Routine immunologic testing performed at time of diagnosis revealed normal complete blood cell count, mild transaminitis from baseline (AST/ALT 61/71 U/L), baseline immunoglobulins, and normal lymphocyte subsets. <h3>Discussion</h3> While KS is a well-known cause of hypogammaglobulinemia, the authors have identified only two other published cases of Burkitt lymphoma in KS. This case emphasizes the importance of oncological screening and that routine immunologic testing of lymphocyte subsets and immunoglobulins may not have abnormalities from baseline in patients with active lymphoma. A mild transaminitis, however, might be concerning for malignancy in these patients.

Fat Grafting in Facial Palsy: A Secondary Revision Technique to Improve the Facial Aesthetics.

Summary:We report our experience of using autologous fat grafting (AFG) as an adjunct to dynamic and static facial reanimation surgical techniques in patients with facial palsy. A consecutive series of patients with facial palsy (congenital or acquired) treated by AFG between September 2007 and October 2017 were reviewed. Multiple strategies for initial dynamic facial reanimation have been utilized. Indications for AFG included asymmetry, volume deficiency, and visible muscle tethering. Standard AFG technique was used with fat harvested from the lower abdomen or thigh and injected into multiple affected areas. Fat grafting was repeated as necessary. Two-dimensional analysis was performed using standardized pre- and postoperative photographs to assess facial symmetry. Patient, surgeon, and independent evaluator satisfaction was recorded using a five-point Likert scale (0–4). Thirty-two patients with a mean age of 43 ± 15.5 years were treated with AFG following facial reanimation. A mean of 1.7 ± 1.4 secondary procedures were performed following initial dynamic reanimation before fat grafting. The average number of AFG episodes was 2.2 ± 1.4 with a mean volume of 12.9 ± 6.0 ml. Minimal complications were seen in either the donor or the recipient sites. There was significant improvement (P ≤ 0.001) of postoperative quantitative facial symmetry following fat grafting. At one-year follow-up, surgeon, patient, and independent evaluator were mostly satisfied (3.06 ± 0.62, 3.31 ± 0.59, and 3.16 ± 0.57, respectively). We report a positive experience of correction of facial asymmetry, contour abnormality and visible muscle pull with fat transplantation following dynamic facial reanimation. The procedure has been shown to be quick and simple, with few complications.

A Protocol For Analysis Of Variations In Maxillary Second Molar Bucco-Palatal Inclination In Cleft Lip And Palate Cases”

Introduction : Facial abnormalities are effected in different facial region, the effect can be variable combination. Maxilla is generally affected in cleft cases, origin can be genetic or influenced by environment. Effected planes can be in three planes transverse, sagittal or vertical. Presurgical or postsurgical orthodontics is indicated in different cases. Presurgical orthodontics proponents emphasized correction of tooth has marked influence in retention and stability of results of interventions performed. In transverse plane it can be buccally or palatally inclined amongst different malocclusion. Our objectives were to evaluate maxillary second molar inclination in Angle’s Class I, Angle’s Class III malocclusion, and unilateral cleft lip and palate patients cases in transverse plane. Material and method : A systematic procedure was followed for the measurement of maxillary second molar inclination in Angle’s Class I, Angle’s Class III malocclusion, and unilateral cleft lip and palate patients. Maxillary second molar inclination was deliberated using protractor assembled on the surveyor. Expected Results : Inclination of second molar in unilateral cleft lip and palate and Class III malocclusion would be comparable. Conclusion : Corrections are performed in transverse plane first, thus emphasizing greater importance of buccopalatal inclination.

Patterns of facial and blink reflex abnormalities in type 2 diabetes mellitus patients with short disease duration: a clue to subclinical cranial neuropathy

Abstract Background Cranial neuropathies occur in 3 to 14% of diabetic patients. Motor conduction study of the facial nerve and blink reflex study are electrophysiologic techniques used to assess the facio-trigeminal pathway in diabetic patients. The patterns of facial and blink reflex abnormalities are inconsistent among studies. This study aimed to assess the subclinical facial nerve and blink reflex abnormalities patterns in short-duration type 2 diabetes mellitus patients. This cross-sectional study included 30 type 2 diabetic patients with disease duration ≤ 5 years. We included only patients with the Toronto clinical neuropathy score ≤ 5. We enrolled 30 age- and sex-matched healthy subjects as a control group. We performed facial nerve motor conduction and blink reflex studies. Patients with prior history of cranial nerve lesions, stroke, or any other disease-causing polyneuropathy or drug-induced neuropathy were excluded from the study. Results Thirty diabetic patients were included, 20 females (66.7%) and ten males (33.3%). Their mean age was 52.63 ± 8.94 years. None of the patients had clinical evidence of neuropathy. There were significant differences between patients and controls in the distal latencies and amplitudes of facial nerve compound muscle action potentials and contralateral R2 late response latencies of the blink reflex. We detected subclinical cranial abnormalities in 6 diabetic patients (20%). One of them (3.3%) had facial nerve conduction abnormalities, four of them (13.4%) had blink reflex abnormalities, and one of them (3.3%) had both facial nerve and blink reflex abnormalities. Conclusion Subclinical cranial neuropathy can occur in short-duration type 2 diabetes mellitus patients. We detected different blink reflex patterns and facial conduction study abnormalities. We recommend blink reflex and facial nerve conduction studies as simple tests for the early evaluation of neurological subclinical affection in patients with short disease duration of T2DM as they may appear in the absence of peripheral neuropathy.

A TNNI2 variant c.525G>T causes distal arthrogryposis in a Chinese family.

Distal arthrogryposis (DA) is a group of congenital autosomal-dominant disorders secondary to defects in joint and muscle function, characterized by multiple joint contractures of the hands and feet. DA can be divided into 10 types according to clinical features. DA has been confirmed to be caused by mutations in genes encoding components of the contractile apparatus of skeletal muscle fibers, such as troponin I2 (TNNI2). In this study, we report a three-generation DA family belonging to the DA2B type. The clinical characteristics of affected members are genetically stable and consistent, with severe deformities in hands and feet, and two affected adults had short stature. None exhibited facial abnormalities. Blood from three affected and three healthy members were collected for whole-exome sequencing and Sanger sequencing. A missense variant in TNNI2 (NM_003282.4: c.525G>T: p.K175N) was successfully identified, which resulted in the substitution of amino acid at position 175 of TNNI2 from lysine to asparagines. The variant c.525G>T in TNNI2 explains the cause of DA in the family. This variant was identified in Chinese people for the first time, and the same variant had been reported in another study but no description of clinical symptoms. Our study comprehensively characterized the c.525G>T variant in TNNI2.

32685 Inhibitory effects of a nature-based skin brightening complex on melanin production utilizing an in vitro skin tissue model

Background: Facial skin pigmentary abnormalities such as uneven skin tone and age spots are considered unaesthetic and a common complaint in women of all skin types. Although effective, traditional depigmenting agents, such as hydroquinone, corticosteroids, and kojic acid, are associated with long-term exposure safety concerns. There is a rising demand to correct irregular skin pigmentation through topical skin care with consumers increasingly interested in natural alternatives. A nature-based skin brightening complex containing Glycyrrhiza glabra, Curcuma longa, and Terminalia chebula was developed for the treatment of hyperpigmentation. Objective: To investigate the skin depigmenting effects of a nature-based complex containing G glabra, C longa, and T chebula. Methods: MelanoDerm tissues (n = 3 each) were treated topically with individual test materials, formulation with and without combined test materials, a positive control (kojic acid), and vehicle and untreated controls for 14 days. Tissues were analyzed for surface reflectance (L*D65) as a measure of skin pigmentation and 10X representative images were obtained to evaluate melanocyte morphology at Day 0, 5, 9 and 14. Melanin content was quantified on Day 14 using the Solvable Melanin Assay. Results: A significant increase in L* was observed in tissues treated with the positive control (on all days) and test materials (on days 9 and 14). Change was not significant with placebo treatment. Tissues treated with the positive control and test materials showed fewer pigmented melanocytes and significantly lower melanin content than the untreated and placebo tissues. Conclusion: The skin depigmenting potential of the nature-based complex has been confirmed in vitro.

EP26.22: First trimester 2D and 3D sonographic imaging of facial abnormalities in holoprosencephaly spectrum

EP26.22: First trimester 2D and 3D sonographic imaging of facial abnormalities in holoprosencephaly spectrum

EXTENSIVE COMPOUND ODONTOMA IN THE MAXILLA

An 11-year-old male patient was referred for evaluation of an asymptomatic lesion in the right maxilla. No gross facial abnormalities were detected in the extraoral examination. Intraoral examination revealed the presence of a firm tumefaction completely lined by unremarkable oral mucosa and leading to obliteration of the right upper vestibule. Panoramic radiograph revealed a well-defined radiopaque area comprised of multiple toothlike structures and impaction of teeth #11 and #13. Given the clinical and radiographic presentation, the diagnostic hypothesis of a compound odontoma was favored. The patient underwent local excision of the lesion, and the following microscopic evaluation confirmed the clinical hypothesis. Subsequently, orthodontic traction of impacted teeth #11 and 13 was pursued with subsequent referral to orthodontic treatment. Five years after initiating treatment, the previously affected maxillary region appears clinically and radiographically unremarkable and the previously impacted teeth are correctly placed in the maxillary arch.

THE IMPORTANCE OF KNOWLEDGE OF CRANIOFACIAL CHARACTERISTICS OF GOLDENHAR SYNDROME FOR ORAL HEALTH TEAMS: A CASE REPORT

Goldenhar syndrome (GS), also known as oculo-auriculo-vertebral dysplasia, is a rare and multiple congenital disorder with yet an unknown etiology. This study describes the case of a 16-year-old girl with characteristics of GS presenting craniofacial deformities, congenital anomalies/malformations/conditions in the left ear classified as microtia, preauricular appendix in the right ear, as well as the presence of epibulbar dermoid in the left eye, in addition to a vertebral pathology (scoliosis, type S). Through panoramic radiography, we observed the presence of included third molars and the shortening of the left mandibular ramus, which explained the facial asymmetry, and ultimately the patient's facial birth defect called hemifacial microsomy. After clinical and radiographic analysis, the person responsible for the patient was informed about the need for periodic follow-up appointments by a multidisciplinary team. The ability of the dentist to recognize facial abnormalities is essential to perform early diagnosis and adequate treatment.

Bilateral Subluxation of Microspherophakic Lens in a Child with Cohen Syndrome

ABSTRACT Cohen Syndrome is a rare autosomal recessive condition characterized by facial abnormalities with or without microcephaly, non-progressive intellectual delay, hypotonia, ophthalmic abnormalities, and neutropenia. Due to its low incidence and variable presentation, much about the disorder, including ophthalmic manifestations, is not fully understood. Here, we present the first documented case of a 5-year-old Amish child with Cohen Syndrome who presented with bilateral subluxation of microspherophakic lenses – rare findings themselves, let alone coexisting in a patient with a rare genetic syndrome. The child underwent bilateral lensectomy and is being managed with aphakic spectacles.

Complicated Facial Fillers: Management Algorithm.

Background:Various materials have been developed as skin fillers to correct wrinkles of the face. Dermal fillers are classified based on their biodegradability into bioresorbable versus nonbioresorbable. All dermal fillers have a potential risk of complications, which can be classified as early and late onset events. Among all the complications of filler injections, inflammatory nodules and granulomas are the most annoying and disfiguring. The purpose of the study was to provide a surgical treatment algorithm that allows us to deal with the complications of facial fillers through three surgical techniques.Methods:Thirty-one patients with complaints of facial contour abnormalities after filler injection, three surgical techniques were adopted according to the presenting case including face lift incision, needle aspiration and intraoral excision after preoperative preparation of the case with postoperative follow-up for 6 months.Results:Among our studied patients treated by these surgical techniques, dissection was difficult owing to the fibrosis and the granulomatous reaction post complicated filler injection. There were two cases of hematoma, 1 case of seroma, and 1 case of facial nerve injury that improved after 4 months, in which marked improvement of facial contour and skin quality was observed.Conclusions:The use of the facelift technique as a surgical treatment for post filler complication granuloma excision provides a useful and satisfactory method for patients complaining of major facial deformities following repeated complicated filler injections. Despite being more difficult than other techniques it is more satisfactory in facial rejuvenation post complicated facial fillers.

Facial Nerve Anomalies as an Obscure Co-occurrence With External Ear Malformations: A Case Report

This study reports an infant with a rare triad of congenital facial palsy, bilateral aural atresia, and middle ear malformations. We highlight the audiological test battery in detail that led to identifying this obscure co-occurrence in a 6-month-old infant. The challenges associated with identifying such rare conditions, especially in infants, can be overcome only by incorporating a meticulous and vigilant approach. The infant was subjected to a series of subjective and objective audiological evaluations, through which rare asymmetric facial grimaces were vigilantly observed. This observation warranted radiologic investigation, which confirmed the suspicion that the anomaly may not be restricted to auditory structures alone. As facial nerve anomalies were confirmed, diversified recommendations, including speech, language, and swallow evaluation, were made apart from the auditory management. Hence in cases of external ear anomalies, although rare, it is essential to rule out facial nerve abnormalities as they can be a concealed problem.

FGD1 Variant Associated With Aarskog-Scott Syndrome.

BackgroundAarskog–Scott syndrome, a rare X-linked genetic disorder, is identified by combined clinical manifestations of short stature, facial, skeletal, and genital anomalies. Annually, two or three new cases are diagnosed with Aarskog–Scott syndrome, which is associated with FGD1 variants. However, there is no specific treatment for Aarskog–Scott syndrome due to its unclear mechanism.MethodsClinical data were collected when the patient first visited the hospital. Trio whole-exome sequencing and Sanger sequencing were performed for the genetic cause of disease. To evaluate the pathogenicity of the variants in vitro, stable cell lines were constructed using lentivirus infection in 143B cell. Furthermore, Western blot was used to verify the expression of signaling pathway-related proteins, and the transcription levels of osteogenic-related genes were verified by luciferase reporter gene assay.ResultsA 7-year-old boy was manifested with facial abnormalities, intellectual disability, and short stature (−3.98 SDS) while the growth hormone level of stimulation test was normal. Trio whole-exome sequencing and Sanger sequencing identified a variant (c.1270A>G, p.Asn424Asp) in FGD1 gene. The Asn424 residue was highly conserved and the hydrogen bond in the FGD1 variant protein has changed, which led to decrease in the interaction with CDC42 protein. In vitro study showed that the Asn424Asp variant significantly decreased the transcription levels of OCN, COL1A1, and ALP activity, and it activated the phosphorylation of JNK1.ConclusionMolecular biological mechanisms between abnormal expression of FGD1and Aarskog–Scott syndrome remain poorly understood. In our study, c.1270A>G variant of FGD1 resulted in Aarskog–Scott syndrome, and the analysis of pathogenicity supports the deleterious effect of the variant. Furthermore, we demonstrated the weakened affinity of the mutant FGD1 and CDC42. Decreased expression of osteogenic-related gene and abnormal activation of JNK1 were also shown in this work.