Three patients with DeSanto-Shinawi syndrome: Further phenotypic delineation.

Somatic truncating variants of the WAC gene have been observed in patients with hematologic malignancies. Furthermore, de novo heterozygous constitutional pathogenic variants of WAC have recently been shown to cause a syndromic form of intellectual disability, DeSanto-Shinawi syndrome. It is unknown whether the constitutional pathogenic variants observed in the intellectual disability syndrome overlap with the somatic pathogenic variants observed in hematologic abnormalities. Herein, we report three patients with constitutional truncating variants of WAC in an attempt to address the above questions. All three of the patients had mild to moderate intellectual disability and dysmorphic features. We then reviewed the phenotypic features of 19 patients with DeSanto-Shinawi syndrome, including the three currently reported ones: eight and seven patients showed a bulbous nasal tip and short fingers, respectively. As for the pathogenetic mechanism, we demonstrated that the expression level of the mRNA derived from the wildtype allele was higher than that derived from the mutated allele, demonstrating nonsense-mediated mRNA decay. This observation makes a haploinsufficiency mechanism likely. Reviews of the constitutional and somatic pathogenic variants observed in patients with hematologic malignancies showed a significant overlap of the two. To date, no patients with DeSanto-Shinawi syndrome have been reported to have developed hematologic abnormalities, except for one of the three patients reported herein who developed leukopenia and thrombocytopenia at the age of 19 years. Larger data sets are required to determine hematologic prognosis of patients with constitutional WAC variants.

Ethnic rhinoplasty.

Rhinoplasty is one of the main facial plastic procedures performed worldwide. Ethnic patients today are mainly mixed-race patients. Diagnosis is based on anatomical findings and surgery should be planned based on patients' needs and what they define as beautiful. Different surgical techniques are presented where a structural approach to rhinoplasty is explained. Very little tissue is resected and support structures of the nose are strengthened with sutures and grafts. A gradual approach to the nasal tip is also presented progressing from simple predictable techniques to more complex unpredictable ones. The final result should be noses with greater definition and refinement that are harmonious and blend in with patients' faces.

Frequency of chromosome 22q11.2 deletion among newborns with non-syndromic congenital heart defects from western Mexico.

BACKGROUND: Congenital heart defects (CHD) are among the most frequent manifestations of 22q11.2 deletion syndrome. Although we found relatively few studies aimed at specifically detecting 22q11.2 deletion in newborns (NB) with CHD, none of them has been performed in Mexico. METHODS: We conducted a prospective hospital-based study from January 2017 to March 2021 in the Genetics and Pediatric Cardiology Services of the Hospital Civil de Guadalajara Dr. Juan I. Menchaca (Guadalajara, Mexico). All consecutive NBs identified with any non-syndromic major CHD confirmed by echocardiography were eligible to participate. A total of 98 NBs were included, 51 males and 47 females. Fluorescence in situ hybridization (FISH) analysis was conducted to search for deletion of chromosome 22q11.2 in interphase nuclei of standard lymphocyte cultures. RESULTS: We found eight patients (8.2%) with CHD and the 22q11.2 deletion, all of them with conotruncal defects, particularly of the truncus arteriosus (p = 0.013), tetralogy of Fallot (p = 0.024), and pulmonary atresia with ventricular septal defect (p = 0.031) subtypes. With de exception of one infant with hypocalcemia and another with hypocalcemia and thymic aplasia, the diagnosis of 22q11.2 deletion was not clinically suspected in the other patients. CONCLUSIONS: Our results confirm the importance of excluding the presence of the 22q11.2 deletion in every NB with CHDs, particularly of the conotruncal subtype, even in the absence of other manifestations.

INTRODUCCIÓN: Las cardiopatías congénitas (CC) son una de las manifestaciones más frecuentes del síndrome de deleción 22q11.2. A pesar de que existen relativamente pocos estudios dirigidos a detectar específicamente la deleción 22q11.2 en recién nacidos (RN) con CC, ninguno de ellos ha sido realizado en México. MÉTODOS: Se realizó un estudio prospectivo de base hospitalaria desde enero de 2017 hasta marzo de 2021 en los Servicios de Genética y Cardiología Pediátrica del Hospital Civil de Guadalajara Dr. Juan I. Menchaca (Guadalajara, México). Todos los RN consecutivos identificados con cualquier tipo de CC mayor no sindrómica confirmada por ecocardiografía fueron elegibles para participar. Se incluyeron 98 recién nacidos, 51 de sexo masculino y 47 de sexo femenino. Mediante el análisis de hibridación fluorescente in situ (FISH, por sus siglas en inglés) se realizó la búsqueda de la deleción del cromosoma 22q11.2 en núcleos en interfase de cultivos de linfocitos estándar. RESULTADOS: Se encontraron ocho pacientes (8.2%) con CC y la deleción 22q11.2, todos ellos con defectos conotruncales, particularmente de los subtipos tronco arterioso (p = 0.013), tetralogía de Fallot (p = 0.024) y atresia pulmonar con comunicación interventricular (p = 0.031). Con excepción de un lactante con hipocalcemia y otro con hipocalcemia y aplasia tímica, el diagnóstico de deleción 22q11.2 no se sospechó clínicamente en los demás pacientes. CONCLUSIONES: Los resultados de este trabajo confirman la importancia de excluir la presencia de la deleción 22q11.2 en todos los RN con CC, particularmente del subtipo conotruncal, incluso en ausencia de otras manifestaciones.

An early diagnosis of trichorhinophalangeal syndrome type 1: a case report and a review of literature.

BACKGROUND: Trichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant disorder caused by defects involving the TRPS1 gene. It exhibits distinctive craniofacial, ectodermal and skeletal abnormalities, such as sparse hair, bulbous nasal tip and short deformed fingers, with extremely variable expressivity. CASE PRESENTATION: We report the case of a 17 months old girl, who presented growth retardation and dysmorphic features. Postnatal growth was always below - 2 Standard Deviation for both weight and length and physical examination revealed relative macrocephaly, sparse hair, bulbous nasal tip, thin upper lip, protruding ears, prominent forehead, small jaw, and short hands and feet. Patient's mother shared the same facial features, and presented sparse hair and small hands. The maternal grandfather and two uncles presented short stature, bulbous nasal tip, thin hair, and premature alopecia. Molecular analysis of TRPS1 gene showed a heterozygous c.2086C > T;(p.Arg696Ter) mutation both in the patient and her mother, confirming the diagnosis of TRPS, type I. CONCLUSIONS: Clinical phenotype of TRPS can be subtle and the syndrome often remains undiagnosed. A comprehensive clinical examination and an exhaustive family history are crucial to reach the correct diagnosis, which is essential to perform adequate follow-up and timely therapeutic procedures.

Frequency of chromosome 22q11.2 deletion among newborns with non-syndromic congenital heart defects from western Mexico / Frecuencia de la deleción del cromosoma 22q11.2 en recién nacidos con cardiopatías congénitas no sindrómicas del occidente de México

Abstract Background: Congenital heart defects (CHD) are among the most frequent manifestations of 22q11.2 deletion syndrome. Although we found relatively few studies aimed at specifically detecting 22q11.2 deletion in newborns (NB) with CHD, none of them has been performed in Mexico. Methods: We conducted a prospective hospital-based study from January 2017 to March 2021 in the Genetics and Pediatric Cardiology Services of the Hospital Civil de Guadalajara Dr. Juan I. Menchaca (Guadalajara, Mexico). All consecutive NBs identified with any non-syndromic major CHD confirmed by echocardiography were eligible to participate. A total of 98 NBs were included, 51 males and 47 females. Fluorescence in situ hybridization (FISH) analysis was conducted to search for deletion of chromosome 22q11.2 in interphase nuclei of standard lymphocyte cultures. Results: We found eight patients (8.2%) with CHD and the 22q11.2 deletion, all of them with conotruncal defects, particularly of the truncus arteriosus (p = 0.013), tetralogy of Fallot (p = 0.024), and pulmonary atresia with ventricular septal defect (p = 0.031) subtypes. With de exception of one infant with hypocalcemia and another with hypocalcemia and thymic aplasia, the diagnosis of 22q11.2 deletion was not clinically suspected in the other patients. Conclusions: Our results confirm the importance of excluding the presence of the 22q11.2 deletion in every NB with CHDs, particularly of the conotruncal subtype, even in the absence of other manifestations.

Resumen Introducción: Las cardiopatías congénitas (CC) son una de las manifestaciones más frecuentes del síndrome de deleción 22q11.2. A pesar de que existen relativamente pocos estudios dirigidos a detectar específicamente la deleción 22q11.2 en recién nacidos (RN) con CC, ninguno de ellos ha sido realizado en México. Métodos: Se realizó un estudio prospectivo de base hospitalaria desde enero de 2017 hasta marzo de 2021 en los Servicios de Genética y Cardiología Pediátrica del Hospital Civil de Guadalajara Dr. Juan I. Menchaca (Guadalajara, México). Todos los RN consecutivos identificados con cualquier tipo de CC mayor no sindrómica confirmada por ecocardiografía fueron elegibles para participar. Se incluyeron 98 recién nacidos, 51 de sexo masculino y 47 de sexo femenino. Mediante el análisis de hibridación fluorescente in situ (FISH, por sus siglas en inglés) se realizó la búsqueda de la deleción del cromosoma 22q11.2 en núcleos en interfase de cultivos de linfocitos estándar. Resultados: Se encontraron ocho pacientes (8.2%) con CC y la deleción 22q11.2, todos ellos con defectos conotruncales, particularmente de los subtipos tronco arterioso (p = 0.013), tetralogía de Fallot (p = 0.024) y atresia pulmonar con comunicación interventricular (p = 0.031). Con excepción de un lactante con hipocalcemia y otro con hipocalcemia y aplasia tímica, el diagnóstico de deleción 22q11.2 no se sospechó clínicamente en los demás pacientes. Conclusiones: Los resultados de este trabajo confirman la importancia de excluir la presencia de la deleción 22q11.2 en todos los RN con CC, particularmente del subtipo conotruncal, incluso en ausencia de otras manifestaciones.

Rhinoplasty in Latino Patients.

Rhinoplasty is the main facial plastic procedure performed in Latin America. Mestizo or Latino patients tend to have noses with thick skin, bulbous tips with poor projection, and flimsy osteocartilaginous underlying frameworks. A technique is presented in which structural grafts are used to strengthen support structures of the nose. A gradual approach is used to obtain tip definition, rotation, and projection using sutures and grafts. Simple techniques are used initially, progressing to more aggressive and less predictable ones in patients who require greater changes. The result should be noses that look more refined, with greater definition, but without looking bigger.

Reshaping of the Broad and Bulbous Nasal Tip.

This article presents a contemporary overview of tip suturing and tip structural grafting techniques used to refine the wide nasal tip. Previous reductive techniques have proved to produce unnatural results over time. It is imperative to correctly evaluate the nose and assess all possible pitfalls during the preoperative period before outlining a surgical plan. Intraoperatively, an algorithmic approach helps obtain a reproducible and refined yet properly narrowed domal tip region with graceful contours that extend laterally to the alar lobule with proper shadowing.

Rhinoplasty in the Mestizo nose.

Mestizo patients are the largest ethnic minority in the United States; the main facial plastic procedure they request is rhinoplasty. Mestizo noses are a challenge. It is common to find bulbous, undefined nasal tips sitting on a poorly structured osteocartilaginous framework. A structural approach is presented whereby support structures of the nose are strengthened and reinforced with structural grafts. A gradual approach to the nasal tip is presented whereby sutures and grafts are used to improve rotation and projection and create more definition. Cases showing long-term results are presented with discussion of the different surgical techniques used.

Rhinoplasty of wide and bulbous nasal tip with a piece of septal cartilage as septal extender / 中华医学美学美容杂志

Objective To evaluate the role of autologous septal cartilage in the rhinoplasty of the wide and bulbous nasal tip. Methods A big piece of autologous nasal septal cartilage was removed and transplanted to the front of nasal septum, acting as a septal extender to fix the nasal alar cartilage,and then the shape of nasal tip was reconstructed by middle crus suture technique, excessive soft tissue under skin of tip and a part of lateral crura cartilage were removed to stand out the shape of the nasal tip. Results After one year follow-up, 118 of 126 cases achieved satisfied effects, but 8 cases dissatisfied because of their undue thick skin. Conclusions This method is reliable in the correction of the wide and bulbous nasal tip.