Your browser doesn't support javascript.
: 20 | 50 | 100
1 - 20 de 153
Sci Rep ; 11(1): 9881, 2021 05 10.
Article En | MEDLINE | ID: mdl-33972643

In children with mandibular hypoplasia, airway management is challenging. However, detailed cephalometric assessment data for this population are sparse. The aim of this study was to find risk factors for predicting difficult airways in children with mandibular hypoplasia, and compare upper airway anatomical differences using three-dimensional computed tomography (3D CT) between children with mandibular hypoplasia and demographically matched healthy controls. There were significant discrepancies in relative tongue position (P < 0.01) and anterior distance of the hyoid bone (P < 0.01) between patients with mandibular hypoplasia and healthy controls. All mandibular measures were significantly different between the two groups, except for the height of the ramus of the mandible. After adjusting for age and sex, the anterior distance of hyoid bone and inferior pogonial angle were significantly associated with a difficult airway (P = 0.01 and P = 0.02). Quantitative analysis of upper airway structures revealed significant discrepancies, including relative tongue position, hyoid distance, and mandible measures between patients with mandibular hypoplasia and healthy controls. The anterior distance of the hyoid bone and inferior pogonial angle may be risk factors for a difficult airway in patients with mandibular hypoplasia.

Airway Management/adverse effects , Critical Illness/therapy , Mandible/diagnostic imaging , Micrognathism/complications , Airway Management/statistics & numerical data , Case-Control Studies , Cephalometry/statistics & numerical data , Child , Child, Preschool , Female , Healthy Volunteers , Humans , Imaging, Three-Dimensional , Infant , Male , Mandible/abnormalities , Micrognathism/diagnosis , Risk Assessment/methods , Risk Assessment/statistics & numerical data , Risk Factors , Tomography, X-Ray Computed , Treatment Failure
Development ; 148(4)2021 02 15.
Article En | MEDLINE | ID: mdl-33589509

Ciliopathies represent a growing class of diseases caused by defects in microtubule-based organelles called primary cilia. Approximately 30% of ciliopathies are characterized by craniofacial phenotypes such as craniosynostosis, cleft lip/palate and micrognathia. Patients with ciliopathic micrognathia experience a particular set of difficulties, including impaired feeding and breathing, and have extremely limited treatment options. To understand the cellular and molecular basis for ciliopathic micrognathia, we used the talpid2 (ta2 ), a bona fide avian model for the human ciliopathy oral-facial-digital syndrome subtype 14. Histological analyses revealed that the onset of ciliopathic micrognathia in ta2 embryos occurred at the earliest stages of mandibular development. Neural crest-derived skeletal progenitor cells were particularly sensitive to a ciliopathic insult, undergoing unchecked passage through the cell cycle and subsequent increased proliferation. Furthermore, whereas neural crest-derived skeletal differentiation was initiated, osteoblast maturation failed to progress to completion. Additional molecular analyses revealed that an imbalance in the ratio of bone deposition and resorption also contributed to ciliopathic micrognathia in ta2 embryos. Thus, our results suggest that ciliopathic micrognathia is a consequence of multiple aberrant cellular processes necessary for skeletal development, and provide potential avenues for future therapeutic treatments.

Bone Remodeling , Ciliopathies/etiology , Micrognathism/etiology , Organogenesis , Phenotype , Animals , Bone Remodeling/genetics , Bone Resorption , Cell Cycle/genetics , Ciliopathies/diagnosis , Craniofacial Abnormalities/genetics , Disease Susceptibility , Embryo, Nonmammalian , Gene Expression Regulation, Developmental , Genetic Association Studies , Hedgehog Proteins/genetics , Hedgehog Proteins/metabolism , Micrognathism/diagnosis , Organogenesis/genetics , Osteoblasts/metabolism , Zinc Finger Protein GLI1/genetics , Zinc Finger Protein GLI1/metabolism
Ear Nose Throat J ; 100(1): NP16-NP20, 2021 Jan.
Article En | MEDLINE | ID: mdl-31159574

INTRODUCTION: Advances in fetal imaging have allowed us to identify abnormalities previously not appreciated. With this study, we hope to identify factors predicting a difficult airway at birth and review the perinatal outcomes of these patients. METHODS: Sixteen patients with antenatally diagnosed micrognathia were reviewed from a tertiary care hospital database from 2011 to 2016. Jaw index (JI), amniotic fluid index (AFI), glossoptosis, gastric size, and oropharynx obliteration were assessed. The airway support required at birth, specialist team involvement, and outcomes were evaluated. RESULTS: Nine (56.3%) of 16 patients had JI <5th percentile, 3 (33.3%) of 9 had difficult intubation, 2 (22.2%) of 9 needed an emergency tracheostomy, and 1 (11.1%) of 9 died. Seven patients had polyhydramnios, 2 (28.6%) of 7 had difficult intubation, 2 (28.6%) of 7 required tracheostomy, and 1 (14.3%) of 7 died. Twelve patients had either JI <5th percentile or abnormal AFI, 5 (41.7%) of 12 had difficult intubation, 2 (16.7%) of 12 required tracheostomy, and 1 (8.33%) of 12 died. For the group without otolaryngology consultation, 8 (50%) of 16, 1 (12.5%) of 8 had difficult intubation and 1 (12.5%) of 8 died because airway was not secured after 45 minutes of resuscitation. CONCLUSION: Jaw index <5th percentile or abnormal AFI predicts a difficult airway. A multidisciplinary approach with otolaryngology involvement for airway intervention may be required at birth.

Airway Obstruction/mortality , Micrognathism/mortality , Airway Obstruction/congenital , Female , Humans , Infant , Infant, Newborn , Intubation, Intratracheal/statistics & numerical data , Male , Micrognathism/diagnosis , Micrognathism/embryology , Polyhydramnios/mortality , Pregnancy , Pregnancy Outcome , Risk Factors , Tertiary Care Centers , Tracheostomy/statistics & numerical data , Ultrasonography, Prenatal
Congenit Anom (Kyoto) ; 60(6): 189-193, 2020 Nov.
Article En | MEDLINE | ID: mdl-32618029

Coffin-Siris syndrome (CSS) is a congenital anomaly syndrome characterized by developmental delay, coarse facial features, and hypoplasia of the fifth digit's nail or phalanges. Herein, we report a case of the 8-year-old female patient who showed developmental delay associated with dysplasia in the macular and large toe area. Comprehensive genomic analysis showed no possible candidate variants, but the subsequent genomic copy number analysis revealed a novel exonic deletion in the coding region of AT-rich interactive domain-containing protein 1B (ARID1B), a gene responsible for CSS. Genomic copy number analysis can aid in diagnosing CSS by confirming undiagnosed exonic deletions in ARID1B. Furthermore, this is the first report of CSS associated with bilateral macular dysplasia.

Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/genetics , DNA-Binding Proteins/genetics , Exons , Face/abnormalities , Hand Deformities, Congenital/diagnosis , Hand Deformities, Congenital/genetics , Intellectual Disability/diagnosis , Intellectual Disability/genetics , Macula Lutea/abnormalities , Micrognathism/diagnosis , Micrognathism/genetics , Neck/abnormalities , Phenotype , Sequence Deletion , Transcription Factors/genetics , Child , Female , Genetic Association Studies , Genetic Predisposition to Disease , Humans
Medicine (Baltimore) ; 99(4): e18648, 2020 Jan.
Article En | MEDLINE | ID: mdl-31977854

RATIONALE: Micrognathia is a subtle facial malformation characterized by a small mandible and receding chin. Fetal micrognathia is often associated with chromosomal abnormalities, skeletal dysplasia, and various syndromes. Once it is dignosised, detailed fetal malformation screening and chromosome examination should be carried out. PATIENT CONCERN: One pregnant woman with suspicion of fetal micrognathia was referred from her local hospital to our hospital for detailed fetal malformation screening and fetal echocardiography. Examination of the fetus was performed using a two-dimensional and three-dimensional ultrasound probe in multiple planes. The fetus showed micrognathia without glossoptosis with features of the inferior facial angle (IFA) ≤50° and his tongue reached anterior mandibular border box during normal movement. DIAGNOSES: The fetus was diagnosed as isolated micrognathia prenatally without multisystem abnormalities. INTERVENTIONS: Amniocentesis was performed and the fetus was found to carry 46XN with 6q14.1 duplication, the significance of which was unclear. OUTCOMES: The fetus was labored through vagina at 38 weeks gestation. A small soft cleft palate was diagnosed after delivery. LESSONS: This case suggests that once prenatal diagnosis of the fetal micrognathia has been made, we should carefully examine the presence of fetus's multisystem developmental abnormalities and due consideration should be given for associated soft cleft palate.

Micrognathism/diagnosis , Ultrasonography, Prenatal/methods , Amniocentesis , Cleft Palate/complications , Cleft Palate/diagnosis , Female , Gestational Age , Humans , Infant, Newborn , Micrognathism/complications , Micrognathism/diagnostic imaging , Palate, Soft/abnormalities , Pregnancy
Eur J Med Genet ; 63(2): 103652, 2020 Feb.
Article En | MEDLINE | ID: mdl-30986546

Meier-Gorlin syndrome (MGS) is a rare autosomal recessive disorder characterized by the triad of short stature, microtia and absent or small patellae. We report on a patient with MGS secondary to biallelic mutations in CDC45 detected on whole exome sequencing (WES). Patients with MGS caused by mutations in CDC45 display a distinct phenotype characterized by craniosynostosis and anorectal malformation. Our patient had craniosynostosis, anorectal malformation and short stature, but did not have the microtia or patella hypoplasia. Our report also highlights the value of WES in aiding diagnosis of patients with rare genetic diseases. In conclusion, our case report and review of the literature illustrates the unique features of CDC45-related MGS as well as the benefits of WES in reducing the diagnostic odyssey for patients with rare genetic disorders.

Cell Cycle Proteins/genetics , Congenital Microtia/diagnosis , Congenital Microtia/genetics , Growth Disorders/diagnosis , Growth Disorders/genetics , Micrognathism/diagnosis , Micrognathism/genetics , Patella/abnormalities , Abnormalities, Multiple/genetics , Abnormalities, Multiple/physiopathology , Anorectal Malformations/genetics , Anorectal Malformations/physiopathology , Craniosynostoses/genetics , Craniosynostoses/physiopathology , Female , Growth Disorders/congenital , Humans , Mutation , Phenotype , Rare Diseases/genetics , Rare Diseases/physiopathology , Whole Exome Sequencing
Am J Med Genet A ; 179(12): 2365-2373, 2019 12.
Article En | MEDLINE | ID: mdl-31509347

Fetal micrognathia can be detected early in pregnancy. Prognosis of micrognathia depends on the risk of respiratory distress at birth and on the long-term risk of intellectual disability. The purpose of this study was to evaluate the long-term prognosis of fetuses with prenatal diagnosis of micrognathia by estimating the prevalence and the severity of confirmed genetic diagnosis in our cohort. Our retrospective study included 41 fetuses with prenatal diagnosis of micrognathia referred to the multidisciplinary centers for prenatal diagnosis in Nice and Marseille, France, between 2006 and 2016. Fetal micrognathia was associated with cleft palate in 27 cases. A genetic cause was confirmed in 21 cases (67%). A chromosomal abnormality was present in 12 cases, including three copy-number variations diagnosed by array CGH. Monogenic disorders were identified in nine cases, most often after birth. Fetuses with family history of micrognathia or Pierre Robin sequence had a favorable outcome. Prognosis was good for the fetuses without associated findings and normal chromosomal analysis, with the exception of one case with a postnatal diagnosis of mandibulofacial dysostosis with microcephaly. Prognostic was poor for the fetuses with additional ultrasound anomalies, as only 5 out of 28 children had a good outcome. Prenatal diagnosis of micrognathia is an indicator of a possible fetal pathology justifying multidisciplinary management. Our study confirms the necessity of performing prenatal array CGH. Use of high-throughput gene sequencing in prenatal period could improve diagnostic performance, prenatal counseling, and adequate postnatal care.

Genetic Association Studies , Genetic Predisposition to Disease , Micrognathism/diagnosis , Micrognathism/genetics , Prenatal Diagnosis , Fetus/abnormalities , Genetic Association Studies/methods , Humans , Magnetic Resonance Imaging , Mandibulofacial Dysostosis/diagnosis , Mandibulofacial Dysostosis/genetics , Patient Outcome Assessment , Phenotype , Prenatal Diagnosis/methods , Retrospective Studies , Ultrasonography, Prenatal
Article En | MEDLINE | ID: mdl-31160358

Coffin-Siris syndrome (CSS) is a developmental disability, caused by genomic variants in the gene SMARCA4, in addition to other known genes, but the full spectrum of SMARCA4 variants that can cause CSS is unknown with 40% of cases not having molecular confirmation. In this report, we identify a patient with CSS, a severe cardiac phenotype, and a novel SMARCA4 variant. There is no experimental structure of human SMARCA4, so we use molecular modeling techniques to generate a structural model of human SMARCA4. We then map known SMARCA4 variants causative of CSS and our novel variant to the model. We use the resulting information to support the interpretation that the novel variant is causative of disease in our patient. Modeling demonstrates that the variant found in our patient is in a region of SMARCA4 associated with DNA binding, as are the other known pathogenic SMARCA4 variants mapped. Because of this structural information, we discuss how these variants may be disease-causing through a dominant negative effect of disrupting DNA binding.

Abnormalities, Multiple/genetics , DNA Helicases/genetics , Face/abnormalities , Hand Deformities, Congenital/genetics , Heart Diseases/genetics , Intellectual Disability/genetics , Micrognathism/genetics , Models, Molecular , Neck/abnormalities , Nuclear Proteins/genetics , Transcription Factors/genetics , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/pathology , Face/pathology , Hand Deformities, Congenital/diagnosis , Hand Deformities, Congenital/pathology , Heart Diseases/congenital , Heart Diseases/diagnosis , Heart Diseases/pathology , Humans , Infant, Newborn , Intellectual Disability/diagnosis , Intellectual Disability/pathology , Male , Micrognathism/diagnosis , Micrognathism/pathology , Mutation , Neck/pathology
Am J Med Genet A ; 179(8): 1637-1641, 2019 08.
Article En | MEDLINE | ID: mdl-31207137

Coffin-Siris syndrome (CSS) is a clinically and genetically heterogeneous developmental disorder, linked to disruption of the BAF chromatin-remodeling complex. Recently, de novo missense and truncating variants have been reported in DPF2 in patients sharing some of the common features of CSS. Here we report a further individual harboring a novel de novo missense DPF2 variant, c.1066T>G, p.Cys356Gly. Structural modeling indicated that the predicted amino acid substitution affects a core residue required for zinc ion coordination and would likely alter the PHD2 domain structure of DPF2. The clinical presentation of Pierre Robin sequence and diaphragmatic hernia did not immediately suggest CSS, with the more common CSS features of hypoplastic toenails and characteristic facial features very subtle. This individual further broadens the phenotypic features of DPF2-related CSS, as well as CSS more generally.

DNA-Binding Proteins/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Mutation , Phenotype , Transcription Factors/genetics , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/genetics , Alleles , Amino Acid Substitution , DNA-Binding Proteins/chemistry , Face/abnormalities , Facies , Genetic Association Studies/methods , Genome , Hand Deformities, Congenital/diagnosis , Hand Deformities, Congenital/genetics , Humans , Intellectual Disability/diagnosis , Intellectual Disability/genetics , Micrognathism/diagnosis , Micrognathism/genetics , Models, Molecular , Neck/abnormalities , Protein Conformation , Structure-Activity Relationship , Transcription Factors/chemistry
Pediatrics ; 144(1)2019 07.
Article En | MEDLINE | ID: mdl-31243159

Coffin-Siris syndrome (CSS) and Nicolaides-Baraitser syndrome (NBS) are 2 overlapping syndromes caused by mutations in genes of the barrier-to-autointegration factor chromatin-remodeling complex, presenting with multiple malformations and intellectual disability. Musculoskeletal changes such as noninflammatory prominence of interphalangeal joints in hands, feet, and, to a lesser extent, knee joints are common in NBS (up to 85%) and also reported in CSS. We present the case of a 7-year-old boy with polyarthritis of several years' duration (without uveitis), developmental delay, microcephaly, and dysmorphic features reminiscent of NBS. Sanger sequencing of the SMARCA2 gene revealed no mutations. Laboratory test results were normal. With synovial biopsy, we confirmed a chronic inflammatory synovitis. Brain MRI revealed dysgenesis of the corpus callosum. Treatment with methotrexate and, subsequently, etanercept led to significant clinical improvement. Whole-exome sequencing revealed a de novo heterozygous nonsense mutation in the ARID1B gene, resulting in a premature stop codon (c.C5404T; p.R1802×), a genotype consistent with CSS. The absence of significantly raised inflammatory markers and a clinical diagnosis of a genetic syndrome associated with noninflammatory joint changes may have contributed to this patient's polyarthritis being missed for several years. We propose that some patients with CSS may have inflammatory arthritis (with or without coexisting skeletal dysplasia), which may be helped by treatment as described herein. Early recognition and treatment of inflammatory arthritis in CSS would have a significant impact on reducing disease burden and improving quality of life for patients with this rare genetic syndrome.

Abnormalities, Multiple/diagnosis , Arthritis/diagnosis , Face/abnormalities , Hand Deformities, Congenital/diagnosis , Intellectual Disability/diagnosis , Micrognathism/diagnosis , Neck/abnormalities , Abnormalities, Multiple/genetics , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthritis/drug therapy , Child , Codon, Nonsense , DNA-Binding Proteins/genetics , Diagnosis, Differential , Etanercept/therapeutic use , Facies , Foot Deformities, Congenital/diagnosis , Hand Deformities, Congenital/genetics , Humans , Hypotrichosis/diagnosis , Intellectual Disability/genetics , Male , Methotrexate/therapeutic use , Micrognathism/genetics , Transcription Factors/genetics
Eur J Med Genet ; 62(11): 103578, 2019 Nov.
Article En | MEDLINE | ID: mdl-30445150

Microphthalmia with limb anomalies (MLA, OMIM, 206920) is a rare autosomal-recessive disease caused by biallelic pathogenic variants in the SMOC1 gene. It is characterized by ocular disorders (microphtalmia or anophtalmia) and limb anomalies (oligodactyly, syndactyly, and synostosis of the 4th and 5th metacarpals), variably associated with long bone hypoplasia, horseshoe kidney, venous anomalies, vertebral anomalies, developmental delay, and intellectual disability. Here, we report the case of a woman who interrupted her pregnancy after ultrasound scans revealed a depression of the frontal bone, posterior fossa anomalies, cerebral ventricular enlargement, cleft spine involving the sacral and lower-lumbar vertebrae, and bilateral microphthalmia. Micrognathia, four fingers in both feet and a slight tibial bowing were added to the clinical picture after fetal autopsy. Exome sequencing identified two variants in the SMOC1 gene, each inherited from one of the parents: c.709G>T - p.(Glu237*) on exon 8 and c.1223G>A - p.(Cys408Tyr) on exon 11, both predicted to be pathogenic by different bioinformatics software. Brain histopathology showed an abnormal cortical neuronal migration, which could be related to the SMOC1 protein function, given its role in cellular signaling, proliferation and migration. Finally, we summarize phenotypic and genetic data of known MLA cases showing that our case has some unique features (Chiari II malformation; focal neuropathological alterations) that could be part of the variable phenotype of SMOC1-associated diseases.

Micrognathism/genetics , Microphthalmos/genetics , Neurons/pathology , Osteonectin/genetics , Adult , Alleles , Brain/diagnostic imaging , Brain/physiopathology , Cell Movement/genetics , Child , Consanguinity , Exons/genetics , Female , Fetus , Homozygote , Humans , Infant , Limb Deformities, Congenital , Male , Micrognathism/diagnosis , Micrognathism/diagnostic imaging , Micrognathism/physiopathology , Microphthalmos/diagnostic imaging , Microphthalmos/physiopathology , Mutation , Pedigree , Sequence Analysis, DNA
Prenat Diagn ; 39(2): 107-115, 2019 01.
Article En | MEDLINE | ID: mdl-30328631

OBJECTIVE: To investigate the intraobserver and interobserver reproducibility of a novel sonographic parameter named facial maxillary angle (FMA) and to establish nomograms of FMA, inferior facial angle (IFA), frontal nasal-mental angle (FNMA), maxilla-nasion-mandible angle (MNMA), and fetal profile line (FPL) in Chinese fetuses. METHODS: In this prospective cross-sectional study, FMA, IFA, FNMA, MNMA, and FPL were measured in 592 normal fetuses between 16 and 36 gestational weeks. FMA was measured twice by the same and another operator with a blinded method on the first 50 cases. The reference interval was defined as ±2SD. The efficacy of five sonographic markers was tested in 10 fetuses with micrognathia retrieved from the database of our unit. RESULTS: The intraclass correlation coefficient (95% CI) of intraobserver and interobserver reproducibility of FMA was 0.937 (0.890-0.964) and 0.891 (0.809-0.938), respectively. FMA, FNMA, and IFA increased slightly from 16 weeks till 28-31 weeks and decreased minimally thereafter. FMA and FNMA made correct diagnosis in all affected fetuses; MNMA and IFA identified nine and eight cases respectively, and FPL only detected five cases. CONCLUSION: A fixed cutoff of 66° for FMA and 136° for FNMA may be adopted as simple screening criteria of micrognathia.

Face/diagnostic imaging , Fetus/diagnostic imaging , Pregnancy Trimester, Second , Pregnancy Trimester, Third , Ultrasonography, Prenatal/methods , Adult , Cephalometry/methods , Cross-Sectional Studies , Face/embryology , Female , Gestational Age , Humans , Mandible/diagnostic imaging , Maxilla/diagnostic imaging , Micrognathism/diagnosis , Micrognathism/pathology , Nose/diagnostic imaging , Pregnancy , Reproducibility of Results
Nat Commun ; 9(1): 4885, 2018 11 20.
Article En | MEDLINE | ID: mdl-30459321

Coffin-Siris and Nicolaides-Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B, SMARCB1, and SMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes. We show that chromosome 6q25 microdeletion syndrome, harboring ARID1B deletions, exhibits a similar CSS/NCBRS methylation profile. Specificity of this epi-signature was confirmed across a wide range of neurodevelopmental conditions including other chromatin remodeling and epigenetic machinery disorders. We demonstrate that a machine-learning model trained on this DNA methylation profile can resolve ambiguous clinical cases, reclassify those with variants of unknown significance, and identify previously undiagnosed subjects through targeted population screening.

Abnormalities, Multiple/genetics , Chromosomal Proteins, Non-Histone/genetics , DNA Methylation , Transcription Factors/genetics , Abnormalities, Multiple/diagnosis , Chromatin Assembly and Disassembly , DNA Helicases/genetics , DNA-Binding Proteins/genetics , Epigenesis, Genetic , Epigenomics , Face/abnormalities , Facies , Foot Deformities, Congenital/diagnosis , Foot Deformities, Congenital/genetics , Hand Deformities, Congenital/diagnosis , Hand Deformities, Congenital/genetics , Humans , Hypotrichosis/diagnosis , Hypotrichosis/genetics , Intellectual Disability/diagnosis , Intellectual Disability/genetics , Micrognathism/diagnosis , Micrognathism/genetics , Mutation , Neck/abnormalities , Nuclear Proteins/genetics , SMARCB1 Protein/genetics , Syndrome
Am J Med Genet A ; 176(8): 1764-1767, 2018 08.
Article En | MEDLINE | ID: mdl-30055038

Coffin-Siris syndrome (CSS) is a rare intellectual disability syndrome classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and other digits, distinctive facial features, hirsutism/hypertrichosis, and sparce scalp hair. It is genetically heterogeneous but most often caused by a pathogenic variant in the ARID1B gene. Previous clinical reports of CSS patients are mainly based on young or middle-aged individuals. Here, we report a 69-year-old woman with CSS phenotype and a pathogenic ARID1B loss-of-function variant c.5259_5260dup. She has severe intellectual disability but otherwise she is in relatively good health both physically and mentally. There is no evident history of chronic illness or progressive disability. CSS appears to be compatible with long survival and most likely it is underdiagnosed in geriatric patients with intellectual disability.

Abnormalities, Multiple/genetics , DNA-Binding Proteins/genetics , Face/abnormalities , Hand Deformities, Congenital/genetics , Intellectual Disability/genetics , Micrognathism/genetics , Neck/abnormalities , Transcription Factors/genetics , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/physiopathology , Aged , Face/physiopathology , Female , Hand Deformities, Congenital/diagnosis , Hand Deformities, Congenital/physiopathology , Humans , Intellectual Disability/diagnosis , Intellectual Disability/physiopathology , Loss of Function Mutation/genetics , Micrognathism/diagnosis , Micrognathism/physiopathology , Neck/physiopathology