RESUMEN
BACKGROUND: Say-Barber-Biesecker-Young-Simpson (SBBYS) (OMIM #603736, Ohdo syndrome variant) is a rare type of severe blepharophimosis intellectual disability syndrome, which is generally characterized by a global developmental delay, distinctive facial features, and intellectual disability with multiple congenital anomalies, including skeletal involvement, missing, or underdeveloped kneecaps, and genital anomalies, in affected males. It has been shown that mutations in the KAT6B gene, which is a lysine acetyltransferase-encoding gene, have been associated with SBBYS syndrome. All the known variants are dominant de novo mutations that result in protein truncation. CASE PRESENTATION: A 14-year-old Iranian Azeri boy with an intellectual disability, distinct dysmorphic facial features such as open-mouth expression, sparse medial eyebrows, widely spaced upward-slanted eyes, epicanthal folds, broad nasal bridge, low-set ears, anteverted ears, short philtrum, hypertelorism, microphthalmia is presented in this case study. Cryptorchidism was reported. Neurologically, the patient presented with poor eye contact, hypotonia, and speech difficulties. In the skeletal X-ray, underdeveloped kneecaps with some new features were observed. CONCLUSION: We present the first case of SBBYS syndrome in association with some new anomaly features in the Iranian population. Based on this diagnosis, we could provide the patient with a suitable plan of management as well as appropriate genetic counseling for his family.
Asunto(s)
Blefarofimosis , Discapacidad Intelectual , Masculino , Humanos , Adolescente , Discapacidad Intelectual/diagnóstico , Blefarofimosis/genética , Blefarofimosis/diagnóstico , Irán , Mutación , Fenotipo , Histona Acetiltransferasas/genéticaRESUMEN
BACKGROUND: Say-Barber-Biesecker-Young-Simpson (SBBYSS) variant of Ohdo syndrome is a rare, autosomal dominant and clinically heterogenous disorder, caused by pathogenic variants in the KAT6B gene located on chromosome 10q22.2. KAT6B encodes a highly conserved histone acetyltransferase belonging to the MYST family. Currently, diseases caused by pathogenic variants in KAT6B (KAT6B-related disorders) comprise two allelic entities: SBBYSS variant of Ohdo syndrome and genitopatellar syndrome (GPS). Increase in the number of cases with overlapping GPS/SBBYSS phenotype which makes it necessary to redefine this group of phenotypes as KAT6B-related disorders or KAT6B spectrum disorders. Individuals with SBBYSS usually present with facial abnormalities, hypotonia, joint laxity, feeding problems, and long thumbs/great toes. This syndrome also typically involves skeletal problems including patellar hypoplasia/agenesis. METHODS: Here we report six SBBYS syndrome patients with the same dysmorphic features but a different course of the disease. One known and five novel KATB6 pathogenic variants were identified by molecular diagnostics using Next Generation Sequencing (NGS). RESULTS: We present a detailed phenotypic analysis of six individuals with KAT6B-related disorders, in whom a heterozygous pathogenic variant in KAT6B gene was found. In all of our patients facial dysmorphism as well as developmental and speech delay were present. Additionally, all but one patients presented with hypotonia, ocular abnormalities and long thumbs. Most of our probands showed blepharophimosis and skeletal (mainly knee) defects. Contrary to previously reported severe patellar defects (hypoplasia/agenesis) anomalies presented by our patients were less severe (dysplasia, habitual dislocation, subluxation) referring to KAT6B-related disorders. CONCLUSION: While most of the anomalies found in our patients comply with SBBYSS criteria, phenotypic differences in our probands support a broader spectrum of the disease phenotype. To establish the range of this spectrum, a detailed analysis of clinical variability among patients with SBBYSS requires further investigation.
Asunto(s)
Discapacidad Intelectual , Hipotonía Muscular , Masculino , Humanos , Mutación , Hipotonía Muscular/genética , Polonia , Discapacidad Intelectual/genética , Histona Acetiltransferasas/genéticaRESUMEN
A patient with global developmental delay and facial abnormality treated in Hunan Maternal and Child Health Care Hospital in September 2018 was diagnosed as a typical Say-Barber-Biesecker/Young-Simpson syndrome (SBBYSS)accompanied with comprehensive clinical manifestations and genetic testing was carried out.The patient carries a heterozygous synonymous mutation of KAT6B gene (NM_012330.3)c.3147G>A (p.P1049P), thus leading to the formation of a new cleavage site (receptor) and forming a new truncated protein.In Chinese, this is the second typical SBBYSS that has been identified and the first prenatal genetic diagnosis has been performed.This study has broadened the mutation spectrum of SBBYSS caused by the mutation of KAT6B gene in Chinese population.
RESUMEN
Genitopatellar syndrome (GPS) is a rare disorder characterized by patellar hypoplasia, flexion contractures of the lower limbs, psychomotor retardation and genital and renal anomalies. We report the case of a female infant diagnosed with GPS to a KAT6B gene mutation, which was identified using whole exome sequencing.
Asunto(s)
Anomalías Craneofaciales/genética , Secuenciación del Exoma/métodos , Histona Acetiltransferasas/genética , Discapacidad Intelectual/genética , Riñón/anomalías , Anomalías Musculoesqueléticas/genética , Mutación/genética , Rótula/anomalías , Trastornos Psicomotores/genética , Escroto/anomalías , Anomalías Urogenitales/genética , Anomalías Craneofaciales/diagnóstico , Femenino , Humanos , Lactante , Discapacidad Intelectual/diagnóstico , Trastornos Psicomotores/diagnóstico , República de Corea , Anomalías Urogenitales/diagnósticoRESUMEN
Genitopatellar syndrome (GPS) is a rare disorder characterized by patellar hypoplasia, flexion contractures of the lower limbs, psychomotor retardation and genital and renal anomalies. We report the case of a female infant diagnosed with GPS to a KAT6B gene mutation, which was identified using whole exome sequencing.
Asunto(s)
Femenino , Humanos , Lactante , Contractura , Exoma , Corea (Geográfico) , Extremidad InferiorRESUMEN
Mutations in KAT6B gene are responsible for Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) and genitopatellar syndrome (GPS), with most mutations occurring in exon 18. A 4-year-old Chinese boy presented with short stature but no other clinical features of SBBYSS or GPS had a de novo novel nonsense pathogenic mutation in exon 14 of the KAT6B gene at position c.2636T>A (p.Leu879X). The correlation analysis of genotype-phenotype indicated distinctive clinical features (short stature, growth hormone deficiency, and delayed bone age) compared with the classical mutations of KAT6B gene. To the best of our knowledge, this is the first report of KAT6B gene mutation in any Chinese individual. This work expands the mutant phenotypic spectrum of the KAT6B gene.
Asunto(s)
Anomalías Múltiples/patología , Blefarofimosis/genética , Blefarofimosis/patología , Hipotiroidismo Congénito/genética , Hipotiroidismo Congénito/patología , Anomalías Craneofaciales/genética , Anomalías Craneofaciales/patología , Cardiopatías Congénitas/genética , Cardiopatías Congénitas/patología , Histona Acetiltransferasas/genética , Discapacidad Intelectual/genética , Discapacidad Intelectual/patología , Inestabilidad de la Articulación/genética , Inestabilidad de la Articulación/patología , Riñón/anomalías , Mutación/genética , Rótula/anomalías , Trastornos Psicomotores/genética , Trastornos Psicomotores/patología , Escroto/anomalías , Anomalías Urogenitales/genética , Anomalías Urogenitales/patología , Anomalías Múltiples/diagnóstico , Anomalías Múltiples/genética , Blefarofimosis/diagnóstico , Preescolar , Codón sin Sentido/genética , Hipotiroidismo Congénito/diagnóstico , Anomalías Craneofaciales/diagnóstico , Exones/genética , Facies , Cardiopatías Congénitas/diagnóstico , Humanos , Discapacidad Intelectual/diagnóstico , Inestabilidad de la Articulación/diagnóstico , Riñón/patología , Masculino , Rótula/patología , Fenotipo , Trastornos Psicomotores/diagnóstico , Escroto/patología , Anomalías Urogenitales/diagnósticoRESUMEN
BACKGROUND: Blepharophimosis is a fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures. It is a rare facial malformation and is considered an important diagnostic feature in dysmorphic analysis. It is likely that many patients with blepharophimosis-mental retardation syndrome have submicroscopic chromosomal rearrangements, and the use of molecular karyotyping can narrow the known blepharophimosis-mental retardation-critical regions or clarify the effect of the haploinsufficiency of the involved genes on the phenotype. MATERIALS AND METHODS: A female patient presented with bilateral blepharophimosis, ptosis, epicanthus inversus, telecanthus, low-set and small ears, other minor anomalies, hypotonia and psychomotor developmental delay. Metabolic investigations and array CGH analysis were performed. The results of molecular karyotyping were confirmed by real-time PCR analysis. RESULTS: Molecular karyotyping revealed a 5.2 Mb deletion in the 10q22.1q22.3 region. Real-time PCR analysis of the proband and her parents confirmed the deletion in the proband and revealed its de novo origin. CONCLUSIONS: With ptosis, hypotonia, and developmental delay as the main diagnostic features of our patient, the effect of histone acetyltransferase-encoding KAT6B gene haploinsufficiency was suspected to have a significant role in determining the phenotype. Detailed clinical characterization of the patient provided additional information on the clinical manifestation of the 10q22 deletion.