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Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) and Genitopatellar syndrome (GTPTS) are very rare conditions caused by KAT6B truncating variants. Because of both syndromes often share common features the associated phenotypes are usually grouped under the term "KAT6B-related disorders." However, particular signs of each syndrome have been reported and their appearance seems to be dependent on where the KAT6B variant is located. Thus, whereas truncating variants associated with SBBYSS have their highest density in the distal part of exon 18, those resulting in GTPTS are distributed between the end of exon 17 and beginning of exon 18. Here, we reported two de novo heterozygous KAT6B truncating variants. The first variant (c.5802delA; p.A1935Pfs*16), identified in a boy with SSBYSS phenotype, resulting in the most distal KAT6B truncating variant reported up-to-date in the scientific literature. The second variant (c.3152delG; p.S1051Tfs*63), located in a region hitherto defined as specific of SBBYSS, seems to cause an overlapping SBBYSS/GTPTS phenotype. The clinical and genetic characterization of these patients could contribute to the understanding of the KAT6B-related disorders., (© 2018 Wiley Periodicals, Inc.)

Lowe syndrome (LS) is a very rare disorder of phosphatidylinositol metabolism, which manifests with a complex phenotype comprising a clinical triad encompassing major abnormalities of the eyes, the kidneys, and the central nervous system. We are reporting a 23-year-old Egyptian male with a severe phenotype of LS with a minimal kidney disease. Direct sequencing of the OCRL gene detected a p.His375Arg mutation in the catalytic domain of the protein. The patient suffered from bilateral congenital cataracts and glaucoma, striking growth deficiency, severe psychomotor disability, a severe osteopathy, and seizures, but only minimal renal dysfunction. Although the biological mechanisms underlying the pathophysiology of LS manifestations is yet unclear, it has been proposed that growth delay and osteopathy are linked to a renal dysfunction. This report, however, argues this association and suggests that kidney dysfunction may partially explain the growth deficiency and bone abnormalities, but other still undefined factors might have a potential impact., (© 2017 Wiley Periodicals, Inc.)

KAT6B sequence variants have been identified in both patients with the Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS) and in the genitopatellar syndrome (GPS). In SBBYSS, they were reported to affect mostly exons 16-18 of KAT6B, and the predicted mechanism of pathogenesis was haploinsufficiency or a partial loss of protein function. Truncating variants in KAT6B leading to GPS appear to cluster within the proximal portion of exon 18, associated with a dominant-negative effect of the mutated protein, most likely. Although SBBYSS and GPS have been initially considered allelic disorders with distinctive genetic and clinical features, there is evidence that they represent two ends of a spectrum of conditions referable as KAT6B-related disorders. We detected a de novo truncating variant within exon 7 of KAT6B in a 8-year-old female who presented with mild intellectual disability, facial dysmorphisms highly consistent with SBBYSS, and skeletal anomalies including exostosis, that are usually considered component manifestations of GPS. Following the clinical diagnosis driven by the striking facial phenotype, we analyzed the KAT6B gene by NGS techniques. The present report highlights the pivotal role of clinical genetics in avoiding clear-cut genotype-phenotype categories in syndromic forms of intellectual disability. In addition, it further supports the evidence that a continuum exists within the clinical spectrum of KAT6B-associated disorders., (© 2017 Wiley Periodicals, Inc.)

Mucolipidosis (ML) II alpha/beta is an autosomal recessive disease caused by reduced enzyme activity of N-acetylglucosamine-1-phosphotransferase. Clinical symptoms of ML II are severe psychomotor delay and dysostosis multiplex; death usually occurs by 5-8 years of age from cardiopulmonary complications. Allogeneic hematopoietic stem cell transplantation (HSCT) has been attempted for ML; however, few reports have documented the detailed outcomes of HSCT for ML. A 26-month-old girl received a human leukocyte antigen 3/6-allele-matched transplant from cord blood. The preparative regimen consisted of fludarabine, cyclophosphamide, 6-Gy total body irradiation, and rabbit antithymocyte globulin. Although comparing before and after cord blood transplantation results, we observed that lysosomal enzyme activities in the plasma decreased by approximately 20-40%. Low serum levels of immunoglobulin A, G2, and G4 were also observed before HSCT; however, these values normalized after transplantation. Despite undergoing HSCT, she was treated twice for bacterial pneumonia with acute respiratory distress syndrome at ages 37 and 38 months. Although HSCT effects on the clinical manifestations were limited, laboratory data including plasma lysosomal enzyme activities and serum levels of immunoglobulin showed improvement., (© 2016 Wiley Periodicals, Inc.)

Pierre Robin sequence (PRS) is a congenital condition with a heterogeneous and imprecise developmental prognosis. We conducted a longitudinal prospective study analyzing the long-term developmental outcome of a consecutive series of 39 children with PRS who had an a priori good prognosis (isolated PRS or PRS associated with a Stickler syndrome) but severe neonatal disorders (respiratory and feeding difficulties). Psychomotor and cognitive levels, speech, and eating behavior were assessed at 15 months of age and 3 and 6 years of age; 24 of the oldest children were interviewed at age 11 or 12 years. Results were analyzed by diagnosis, extent of respiratory and feeding disorders, and treatment modalities. Cognitive scores were within normal ranges and increased over time, from 90.5 at 15 months of age to 109.1 at 6 years. The 24 oldest children were enrolled in the appropriate junior high school grade at the normal age. For children 15 months of age, language scores were below the average, as were scores for vocabulary at 3 years for half of the patients. At 6 years, children's speech showed persistent rhinolalia, which was mild (47%), moderate (11%), or major (11%). At 15 months of age, 74% of the children had satisfactory eating behavior, and 15% had serious difficulties. At 3 and 6 years, 18% and 6% of the children, respectively, had eating problems. Treatment modalities had no significant effect on long-term outcome. Global developmental quotient scores were lower but not significantly for children with an associated Stickler syndrome than those with isolated PRS. Children with isolated PRS showed good prognosis., (Copyright © 2013 Wiley Periodicals, Inc.)

49, XXXXY is a rare chromosomal syndrome due to double nondisjunction of the replicating X chromosome. Considered a severe variant of XXY or Klinefelter syndrome, boys with this chromosome constitution are assumed to have severe mental retardation (MR) in addition to craniofacial, genital, endocrine, and heart abnormalities. Here, we present a multidisciplinary analysis including the clinical and neurobehavioral aspects of this condition in 20 boys with 49, XXXXY who share a common phenotype and neurobehavioral profile. The phenotypic presentation of the boys with 49, XXXXY shares some characteristics with 47, XXY, but there are also other unique and distinctive features. Previously unappreciated intact nonverbal skills are evident in conjunction with moderate to severe developmental dyspraxia. Variability in clinical and cognitive functioning may reflect skewed X inactivation, mosaicism, or other factors that warrant further investigation., ((c) 2010 Wiley-Liss, Inc.)

The purpose of the study was to delineate the anomalies and the natural life history of persons with the Bowen-Conradi syndrome [Bowen and Conradi 1976: Birth Defects: Orig Artic Ser XII(6):101-108]. We ascertained 39 cases and personally examined almost all. For those who were not seen, their clinical record were scrutinized. Pedigree analysis of all 39 was done and kinship coefficients computed. The birth prevalence was estimated to be 1/355 live births., (Copyright 2003 Wiley-Liss, Inc.)