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European Journal of Pediatrics May 2024Patients with Aarskog-Scott syndrome (AAS) have short stature, facial anomalies, skeletal deformities, and genitourinary malformations. FYVE, RhoGEF, and PH... (Review)
Review
Patients with Aarskog-Scott syndrome (AAS) have short stature, facial anomalies, skeletal deformities, and genitourinary malformations. FYVE, RhoGEF, and PH domain-containing 1 (FGD1) is the only known causative gene of AAS. However, the diagnosis of AAS remains difficult, and specific treatments are still absent. Patients suspected with AAS were recruited, and clinical information was collected. Genetic testing and functional analysis were carried out for the diagnosis. By literature review, we summarized the clinical and genetic characteristics of FGD1-related AAS and analyzed the genotype-phenotype correlation. Five patients were recruited, and four novel FGD1 variants were identified. The diagnosis of AAS was confirmed by genetic analysis and functional study. Three patients treated with growth hormone showed improved heights during the follow-up period. By literature review, clinical features of AAS patients with FGD1 variants were summarized. Regarding FGD1 variations, substitutions were the most common form, and among them, missense variants were the most frequent. Moreover, we found patients with drastic variants showed higher incidences of foot and genitourinary malformations. Missense variants in DH domain were related to a lower incidence of cryptorchidism. Conclusion: We reported four novel pathogenic FGD1 variations in AAS patients and confirmed the efficacy and safety of growth hormone treatment in FGD1-related AAS patients with growth hormone deficiency. Additionally, our literature review suggested the crucial role of DH domain in FGD1 function. What is Known: • Aarskog-Scott syndrome is a rare genetic disease, and the only known cause is the variant in FGD1 gene. The typical clinical manifestations of AAS include facial, skeletal, and urogenital deformities and short stature. What is New: • We reported four novel FGD1 variants and reported the treatment of growth hormone in FGD1-related AAS patients. Our genotype-phenotype correlation analysis suggested the crucial role of DH domain in FGD1 function.
Topics: Child; Child, Preschool; Female; Humans; Male; Abnormalities, Multiple; Dwarfism; Face; Genetic Association Studies; Genetic Diseases, X-Linked; Genitalia, Male; Guanine Nucleotide Exchange Factors; Hand Deformities, Congenital; Heart Defects, Congenital; Phenotype; Scalp Dermatoses; Urogenital Abnormalities
PubMed: 38411716
DOI: 10.1007/s00431-024-05484-9 -
European Journal of Paediatric Dentistry Sep 2023Aarskog-Scott syndrome (AAS) is a rare developmental disorder characterised by facial dysmorphism, genital and limb anomalies as well as disproportionate acromelic short...
BACKGROUND
Aarskog-Scott syndrome (AAS) is a rare developmental disorder characterised by facial dysmorphism, genital and limb anomalies as well as disproportionate acromelic short stature. Clinical diagnosis is based on physical examination and the presence of the most characteristic clinical signs. The diagnosis can be finally confirmed by molecular tests, which identify mutations in the FGD1 gene.
CASE REPORT
The report outlines the orthodontic treatment of a 6-year-old male patient, who was diagnosed with AAS syndrome. He presents all facial and oral clinical signs of this syndrome. The extent of maxillary hypoplasia and early dental crowding are so significant that immediate expansion therapy is required.
CONCLUSION
Dental management of patients with AAS syndrome represents a challenge for paediatric dentists. The key to improving a patient's aesthetic, functional and psychological condition is making the correct orthodontic decision.
Topics: Male; Child; Humans; Guanine Nucleotide Exchange Factors; Mutation; Dwarfism; Genitalia, Male
PubMed: 37337880
DOI: 10.23804/ejpd.2023.1953 -
American Journal of Medical Genetics.... Jul 2022Aarskog-Scott syndrome (AAS) is a developmental disorder, caused by disease-causing hemizygous variants in the FGD1 gene. AAS is characterized by dysmorphic features,...
Aarskog-Scott syndrome (AAS) is a developmental disorder, caused by disease-causing hemizygous variants in the FGD1 gene. AAS is characterized by dysmorphic features, genital malformation, skeletal anomalies, and in some cases, intellectual disability and behavioral difficulties. Myopathy has only been reported once in two affected siblings diagnosed with AAS. Only few adult cases have been reported. This article reports four adults with AAS (three male cases and one female carrier) from two unrelated Danish families, all males presented with variable features suggestive of myopathy. All four carried novel hemizygous pathogenic variants in the FGD1 gene; one family presented with the c.2266dup, p.Cys756Leufs*19 variant while the c.527dup; p.Leu177Thrfs*40 variant was detected in the second family. All males had some mild myopathic symptoms or histological abnormalities. Case 1 had the most severe myopathic phenotype with prominent proximal muscular fatigue and exercise intolerance. In addition, he had multiple deletions of mtDNA and low respiratory chain activity. His younger nephew, case 3, had difficulties doing sports in his youth and had a mildly abnormal muscle biopsy and relatively decreased mitochondrial enzyme activity. The singular case from family 2 (case 4), had a mildly myopathic muscle biopsy, but no overt myopathic symptoms. Our findings suggest that myopathic involvement should be considered in AAS.
Topics: Adult; Denmark; Dwarfism; Face; Female; Genetic Diseases, X-Linked; Genitalia, Male; Guanine Nucleotide Exchange Factors; Hand Deformities, Congenital; Heart Defects, Congenital; Humans; Male; Syndrome
PubMed: 35388608
DOI: 10.1002/ajmg.a.62753 -
Saudi Journal of Anaesthesia 2021Aarskog Scott syndrome is a rare genetic disorder characterised by facial, limb and genital abnormalities first described in 1970. Its evolving nature in terms of...
Aarskog Scott syndrome is a rare genetic disorder characterised by facial, limb and genital abnormalities first described in 1970. Its evolving nature in terms of associated features and increased surgical interventions necessitates anaesthesiologists to have a thorough knowledge about this syndrome for a better preparedness. Although multiple case reports have been published in literature since its discovery, no case report regarding its anaesthetic considerations and challenges have been described in literature till now. We report challenges encountered and successful anaesthetic management of a seven-year-old girl with Aarskog Scott Syndrome posted for a corneal repair in view of traumatic corneal perforation.
PubMed: 34188646
DOI: 10.4103/sja.sja_1047_20 -
Genetics Research 2021Aarskog-Scott syndrome is a genetically and clinically heterogeneous rare condition caused by a pathogenic variant in the FGD1 gene. A systematic review was carried out... (Review)
Review
Aarskog-Scott syndrome is a genetically and clinically heterogeneous rare condition caused by a pathogenic variant in the FGD1 gene. A systematic review was carried out to analyse the prevalence of clinical manifestations found in patients, as well as to evaluate the genotype-phenotype correlation. The results obtained show that clinical findings of the craniofacial, orthopaedic, and genitourinary tract correspond to the highest scores of prevalence. The authors reclassified the primary, secondary, and additional criteria based on their prevalence. Furthermore, it was possible to observe, in accordance with previous reports, that the reported phenotypes do not present a direct relation to the underlying genotypes.
Topics: Dwarfism; Face; Genetic Association Studies; Genetic Diseases, X-Linked; Genitalia, Male; Guanine Nucleotide Exchange Factors; Hand Deformities, Congenital; Heart Defects, Congenital; Humans; Male; Mutation; Prevalence
PubMed: 33762894
DOI: 10.1155/2021/6652957 -
BMJ Case Reports Jun 2020Aarskog-Scott syndrome (AAS), also known as facio-genital dysplasia or faciodigitogenital syndrome, is a rare genetic disorder clinically characterised by facial, limb...
Aarskog-Scott syndrome (AAS), also known as facio-genital dysplasia or faciodigitogenital syndrome, is a rare genetic disorder clinically characterised by facial, limb and genitalanomalies. Although also autosomal dominance and recessive patterns have been reported, up to now, only an X linked form associated to mutations of the gene has been recognised as causative for this syndrome.In this case report, we describe a large Italian family in which three members across three generations show classical features of the syndrome. The youngest patient, the proband, and his mother were both molecularly studied and characterised for the not previously reported variant c.1828C>T (p. Arg610*) in the gene but with the classic phenotype of AAS. Additionally, both the proband and his mother present a 2.5 Mb 16p13.11-p12.3 microduplication, a genetic variant still unclear for the phenotypic consequences: the co-occurrence of the two rare conditions is discussed for the possible clinical significance.
Topics: Abnormalities, Multiple; Adult; Biological Variation, Population; Child Development; Diagnosis, Differential; Dwarfism; Face; Female; Genes, Duplicate; Genetic Diseases, X-Linked; Genitalia, Male; Guanine Nucleotide Exchange Factors; Hand Deformities, Congenital; Heart Defects, Congenital; Humans; Infant; Male; Mutation; Patient Care Management; Pedigree; Psychosocial Support Systems
PubMed: 32606125
DOI: 10.1136/bcr-2020-235183 -
Journal of Clinical and Diagnostic... Dec 2016Aarskog syndrome also known as Aarskog-Scott Syndrome, Facio-digito-genital Syndrome or Faciogenital Dysplasia is a rare, X-linked disorder predominantly affecting...
Aarskog syndrome also known as Aarskog-Scott Syndrome, Facio-digito-genital Syndrome or Faciogenital Dysplasia is a rare, X-linked disorder predominantly affecting males, characterized by facial, skeletal and genital anomalies. This is a case report of a 15-year-old male patient who visited our college complaining of poor facial aesthetics. History revealed consanguinity and his sibling to be suffering from the same. A diagnosis of Aarskog syndrome was made based upon the detailed patient history, thorough clinical evaluation and identification of characteristic findings in radiographs. Professional counselling explained him the nature of his condition and treatment options to correct dental anomalies and congenital malformations were advised.
PubMed: 28209013
DOI: 10.7860/JCDR/2016/22180.8982 -
BMC Pediatrics Jan 2017The X-linked condition "Aarskog-Scott syndrome (AAS)" causes a characteristic combination of short stature, facial, genital and skeletal anomalies. Studies elucidated a...
BACKGROUND
The X-linked condition "Aarskog-Scott syndrome (AAS)" causes a characteristic combination of short stature, facial, genital and skeletal anomalies. Studies elucidated a causative link between AAS and mutations in the FGD1 gene, which encodes a Rho/Rac guanine exchange factor. FGD1 is involved in regulating signaling pathways that control cytoskeleton organization and embryogenesis.
CASE PRESENTATION
FGD1 was studied in an Emirati family with two cases of AAS using PCR amplification and direct sequencing of the entire coding region of the gene. Various in silico tools were also used to predict the functional consequences of FGD1 mutations. In the reported family, two brothers harbor a novel hemizygous mutation in FGD1 c.53del (p.Pro18Argfs*106) for which the mother is heterozygous. This frameshift deletion, being close to N-terminus of FGD1, is predicted to shift the reading frame in a way that it translates to 105 erroneous amino acids followed by a premature stop codon at position 106. Full molecular and clinical accounts about the variant are given so as to expand molecular and phenotypical knowledge about this disorder.
CONCLUSIONS
A novel variant in FGD1 was found in an Emirati family with two brothers suffering from AAS. The variant is predicted to be a null mutation, and this is the first report of its kind from the United Arab Emirates.
Topics: Base Sequence; Child; Child, Preschool; Dwarfism; Face; Frameshift Mutation; Genetic Diseases, X-Linked; Genetic Markers; Genitalia, Male; Guanine Nucleotide Exchange Factors; Hand Deformities, Congenital; Heart Defects, Congenital; Humans; Male; Sequence Deletion; United Arab Emirates
PubMed: 28103835
DOI: 10.1186/s12887-017-0781-4 -
Colombia Medica (Cali, Colombia) Dec 2015To present descriptive epidemiology of Orofacial Clefts and to determine the association of syndromic forms with antenatal high-risk conditions, preterm birth, and...
OBJECTIVES
To present descriptive epidemiology of Orofacial Clefts and to determine the association of syndromic forms with antenatal high-risk conditions, preterm birth, and comorbidities among nested-series of cases.
METHODS
A study of nested-series of cases was conducted. Frequencies of cleft type, associated congenital anomalies, syndromic, non-syndromic and multiple malformation forms, and distribution of Orofacial Clefts according to sex and affected-side were determined. Odds ratios were calculated as measures of association between syndromic forms and antenatal high-risk conditions, preterm birth and comorbidities. A total of three hundred and eleven patients with Orofacial Clefts were assessed in a 12-month period.
RESULTS
The most frequent type of Orofacial Clefts was cleft lip and palate, this type of cleft was more frequent in males, whereas cleft palate occurred more often in females. The most common cases occurred as non-syndromic forms. Aarskog-Scott syndrome showed the highest frequency amongst syndromic forms. Hypertensive disorders in pregnancy, developmental dysplasia of the hip, central nervous diseases and respiratory failure showed significant statistical associations (p <0.05) with syndromic forms.
CONCLUSIONS
These data provide an epidemiological reference of Orofacial Clefts in Colombia. Novel associations between syndromic forms and clinical variables are determined. In order to investigate causality relationships between these variables further studies must be carried out.
Topics: Adolescent; Adult; Age Distribution; Child; Child, Preschool; Cleft Lip; Cleft Palate; Colombia; Dwarfism; Face; Female; Genetic Diseases, X-Linked; Genitalia, Male; Hand Deformities, Congenital; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Male; Middle Aged; Sex Distribution; Syndrome
PubMed: 26848196
DOI: No ID Found -
NMC Case Report Journal Jul 2015A 44-year-old male with Aarskog syndrome (AS) presented with subarachnoid hemorrhage secondary to ruptured posterior communicating artery aneurysm. AS, also known as...
A 44-year-old male with Aarskog syndrome (AS) presented with subarachnoid hemorrhage secondary to ruptured posterior communicating artery aneurysm. AS, also known as faciogenital dysplasia, is an X-linked, autosomal dominant or autosomal recessive congenital developmental disorder. This syndrome is characterized by short stature in association with a variety of multiple anomalies in musculoskeletal, neurological, and urogenital systems. Cerebrovascular abnormalities such as anomalous cerebral venous drainage, dysplastic internal carotid artery, and basilar artery malformation have been reported to be associated with AS. To our knowledge this represents the first case of a ruptured intracranial aneurysm in a patient with AS.
PubMed: 28663972
DOI: 10.2176/nmccrj.2014-0022