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(A) + (B) High eyebrow arch, wide eye distance, small eye fissure, double eyelid ptosis, flat nose bridge and slightly upturned nostrils; the middle sulcus was wide and long, and the ear was low and backward. (C) + (D) Hands/soles were small; fingers/toes were short and thick; little fingers on both hands were short and curved with a single finger fold. (E) Bilateral oblique inguinal hernia and shapeless scrotum complicated with cryptorchidism (after surgery). (F) Sacral tail skin depression. (G) Sternum depression, costal margin eversion and a flat navel.
Source publication
Aarskog-Scott syndrome is a rare genetic disorder characterized by short stature, abnormal facial features, and digital and genital deformities. FGD1 gene variation is the known cause of this disorder. This paper described a Chinese family study of Aarskog-Scott syndrome in which the main patients were two brothers. Then, the relationship between g...
Citations
... However, the available data were still limited. There were only three FGD1-related AAS patients reported to receive rhGH treatment, with two patients having improved height [18][19][20]. In our study, rhGH treatment showed height improvement in the patients, and there were no serious adverse reactions during the treatment. ...
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.
