Xp22.33p22.13 Duplication in a Male Patient Carrying a Recombinant X Chromosome Derived from an Inherited Intrachromosomal Insertion.

Intrachromosomal insertions are complex structural rearrangements that are challenging to interpret using classical cytogenetic methods. We report a male patient carrying a recombinant X chromosome derived from a maternally inherited intrachromosomal insertion. The patient exhibited developmental delay, intellectual disability, behavioral disorder, and dysmorphic facial features. To accurately identify the rearrangements in the abnormal X chromosome, additional cytogenetic studies were conducted, including fluorescence in situ hybridization (FISH), multicolor-banding FISH, and array comparative genomic hybridization. The results showed a recombinant X chromosome, resulting in a 13.05 Mb interstitial duplication of segment Xp22.33-Xp22.13, which was inserted at cytoband Xq26.1. The duplicated region encompasses 99 genes, some of which are associated with the patient's clinical manifestations. We propose that the combined effects of the Xp-duplicated genes may contribute to the patient's phenotype.

Oculo-auriculo-vertebral spectrum associated with aberrant subclavian artery in an infant with recurrent respiratory distress / Espectro oculoauriculovertebral associado à artéria subclávia aberrante em lactente com desconforto respiratório recorrente

ABSTRACT Objective: To describe an infant with craniofacial microsomia and recurrent respiratory distress associated with aberrant right subclavian artery in order to review its most frequent congenital anomalies and alert the pediatrician to its rarer and more severe complications. Case description: This case report involves an 18-month-old male infant, only son of non-consanguineous parents. At birth, the child presented craniofacial dysmorphisms (facial asymmetry, maxillary and mandibular hypoplasia, macrostomia, grade 3 microtia, and accessory preauricular tag) restricted to the right side of the face. Additional tests showed asymmetric hypoplasia of facial structures and thoracic hemivertebrae. No cytogenetic or cytogenomic abnormalities were identified. The patient progressed to several episodes of respiratory distress, stridor, and nausea, even after undergoing gastrostomy and tracheostomy in the neonatal period. Investigation guided by respiratory symptoms identified compression of the esophagus and trachea by an aberrant right subclavian artery. After surgical correction of this anomaly, the infant has not presented respiratory symptoms and remains under multidisciplinary follow-up, seeking rehabilitation. Comments: Craniofacial microsomia presents a wide phenotypic variability compared to both craniofacial and extracraniofacial malformations. The latter, similarly to the aberrant right subclavian artery, is rarer and associated with morbidity and mortality. The main contribution of this case report was the identification of a rare anomaly, integrating a set of malformations of a relatively common condition, responsible for a very frequent complaint in pediatric care.

RESUMO Objetivo: Descrever lactente com microssomia craniofacial e desconforto respiratório recorrente associado à artéria subclávia direita aberrante, com o intuito de revisar as anomalias congênitas mais frequentes e alertar o pediatra sobre suas complicações mais raras e de maior gravidade. Descrição do caso: Lactente do sexo masculino, 18 meses de idade e filho único de casal não consanguíneo. Ao nascimento, foram observadas dismorfias craniofaciais (assimetria facial, hipoplasia maxilar e mandibular, macrostomia, microtia grau 3 e apêndice na linha trago-oral) restritas ao lado direito da face. Os exames complementares evidenciaram hipoplasia assimétrica da face e hemivértebras torácicas. Não foram identificadas anormalidades citogenéticas ou citogenômicas. O paciente evoluiu com diversos episódios de desconforto respiratório, estridor e náuseas, mesmo tendo realizado gastrostomia e traqueostomia no período neonatal. A investigação direcionada para os sintomas respiratórios identificou a compressão de esôfago e traqueia por uma artéria subclávia direita aberrante. Após a correção cirúrgica dessa anomalia, o lactente não tem apresentado sintomas respiratórios e mantém seguimento multidisciplinar buscando reabilitação. Comentários: A microssomia craniofacial apresenta grande heterogeneidade fenotípica em relação às malformações tanto craniofaciais como extracraniofaciais. Estas últimas, como a artéria subclávia direita aberrante, são mais raras e associadas à morbimortalidade. A principal contribuição deste relato de caso foi o reconhecimento de uma anomalia rara, integrando um conjunto de malformações de uma condição relativamente comum e sendo responsável por uma queixa muito frequente no atendimento pediátrico.

OCULO-AURICULO-VERTEBRAL SPECTRUM ASSOCIATED WITH ABERRANT SUBCLAVIAN ARTERY IN AN INFANT WITH RECURRENT RESPIRATORY DISTRESS.

OBJECTIVE: To describe an infant with craniofacial microsomia and recurrent respiratory distress associated with aberrant right subclavian artery in order to review its most frequent congenital anomalies and alert the pediatrician to its rarer and more severe complications. CASE DESCRIPTION: This case report involves an 18-month-old male infant, only son of non-consanguineous parents. At birth, the child presented craniofacial dysmorphisms (facial asymmetry, maxillary and mandibular hypoplasia, macrostomia, grade 3 microtia, and accessory preauricular tag) restricted to the right side of the face. Additional tests showed asymmetric hypoplasia of facial structures and thoracic hemivertebrae. No cytogenetic or cytogenomic abnormalities were identified. The patient progressed to several episodes of respiratory distress, stridor, and nausea, even after undergoing gastrostomy and tracheostomy in the neonatal period. Investigation guided by respiratory symptoms identified compression of the esophagus and trachea by an aberrant right subclavian artery. After surgical correction of this anomaly, the infant has not presented respiratory symptoms and remains under multidisciplinary follow-up, seeking rehabilitation. COMMENTS: Craniofacial microsomia presents a wide phenotypic variability compared to both craniofacial and extracraniofacial malformations. The latter, similarly to the aberrant right subclavian artery, is rarer and associated with morbidity and mortality. The main contribution of this case report was the identification of a rare anomaly, integrating a set of malformations of a relatively common condition, responsible for a very frequent complaint in pediatric care.

Mucopolysaccharidosis VII in Brazil: natural history and clinical findings.

BACKGROUND: Mucopolysaccharidosis type VII (MPS VII), also known as Sly syndrome, caused by deficiency of the lysosomal enzyme ß-glucuronidase, is an ultra-rare disorder with scarce epidemiological data and few publications about natural history and clinical spectrum. METHODS: We conducted a case series report which included retrospective data from all MPS VII patients diagnosed through the "MPS Brazil Network" who were known to be alive in 2020 in Brazil (N = 13). Clinical data were obtained from a review of the medical records and descriptive statistics and variables were summarized using counts and percentages of the total population. RESULTS: The majority of the patients were from the Northeast region of Brazil. Among the signs and symptoms that raised the clinical suspicion of MPS, coarse face was the most frequent; 58% of the patients had a history of non-immune hydrops fetalis. All the subjects presented short neck and trunk. The majority presented typical phenotypical signs of MPS disorders. They all presented neurodevelopmental delay and cognitive impairment. About half of this cohort had knees deformities. Dysostosis multiplex was identified in almost all patients and cardiomyopathy was less frequent than observed in other types of MPSs. The mean age at diagnosis was 5 years, ranging from 1 to 14 years. Almost all patients (12/13) were homozygous for the c.526C>T (p.Leu176Phe) mutation. A novel variant of the GUSB gene was found, the c.875T>C (p.Leu292Pro), in a compound heterozygous with the c.526C>T (p.Leu176Phe) variant. CONCLUSIONS: This case series is the biggest data collection of MPS VII patients alive in Latin America. The overall clinical picture of the MPS VII patients is very similar to other MPS disorders, including a spectrum of severity and delayed diagnosis.

Contribution of SLC26A4 to the molecular diagnosis of nonsyndromic prelingual sensorineural hearing loss in a Brazilian cohort.

OBJECTIVE: Hereditary hearing loss (HL) is the most common sensorineural disorder in humans. Besides mutations in GJB2 and GJB6 genes, pathogenic variants in the SLC26A4 gene have been reported as a cause of hereditary HL due to its role in the physiology of the inner ear. In this research we wanted to investigate the prevalence of mutations in SLC26A4 in Brazilian patients with nonsyndromic prelingual sensorineural HL. We applied the high-resolution melting technique to screen 88 DNA samples from unrelated deaf individuals that were previously screened for GJB2, GJB6 and MT-RNR1 mutations. RESULTS: The frequency of mutations in the SLC26A4 gene was 28.4%. Two novel mutations were found: p.Ile254Val and p.Asn382Lys. The mutation c.-66C>G (rs17154282) in the promoter region of SLC26A4, was the most frequent mutation found and was significantly associated with nonsyndromic prelingual sensorineural HL. After mutations in the GJB2, GJB6 and mitochondrial genes, SLC26A4 mutations are considered the next most common cause of hereditary HL in Brazilian as well as in other populations, which corroborates with our data. Furthermore, we suggest the inclusion of the SCL26A4 gene in the investigation of hereditary HL since there was an increase in the frequency of the mutations found, up to 22.7%.

Erratum to: Familial chromosomal translocation X; 22 associated with infertility and recurrent X mosaicism.

[This corrects the article DOI: 10.1186/s13039-016-0249-5.].

Familial chromosomal translocation X; 22 associated with infertility and recurrent X mosaicism.

BACKGROUND: Individuals with apparently balanced translocations, often, show no clinical findings. However, in meiosis, translocations tend to cause errors on chromosome disjunction and the ones involving sex chromosomes have particular implications for the phenotype. Male carriers of balanced X-autosome translocations are almost invariably infertile due to interruption of the spermatogenesis, but the mechanism is not fully understood. CASE PRESENTATION: In this case report, we performed a combination of classical cytogenetics (G-banding), molecular cytogenetics (fluorescence in situ hybridization and X-chromosome inactivation study), and cytogenomics (microarray-based comparative genomic hybridization) techniques for characterization of an inherited (X;22) translocation in a family originally referred for infertility investigation. Both proband and his sister are infertile and present the maternally inherited translocation. Interestingly, the maternal grandmother was mosaic for X chromosome monosomy suggesting that the t(X;22) in the proband's mother arose by errors at oogenesis. The presence of the same mosaicism of the X chromosome in the proband's aunt is consistent with this consideration. Array- CGH analysis showed no constitutional pathogenic gains or losses in the translocation carriers. The X-chromosome inactivation studies revealed that the translocated X;22 was active in 99.3% of cells in the mother and in 88% of cells in the daughter. We suggest that incomplete skewing of X inactivation (>97 %) of the daughter could justify the infertility. This study is the first description of recurrent mosaicism of the X chromosome associated with a familial X-autosome translocation. CONCLUSIONS: The phenotype of infertility was probably caused by disruption of spermatogenesis due to gametogenesis specific errors resulted from meiotic pairing and segregation anomalies on the translocated chromosomes.