Pseudo-Roberts Syndrome: An Entity or Not?

Background: Roberts syndrome is a genetic disorder characterized by tetra-phocomelia with abnormalities of ESCO2. We report a male stillborn with tetra-phocomelia and no ESCO2 mutation. Case report: Pre- and post-natal imaging and autopsy findings included schizencephaly, phocomelia of four limbs, micrognathia, oligodactyly, and cardiopulmonary malformations. Microcephaly on pre-natal imaging was not confirmed by autopsy examination. Karyotype, prenatal chromosome microarray and ESCO2 gene testing were normal. Conclusion: Given the various skeletal anomalies found on autopsy and imaging evaluations, at least phenotypically, our case appeared to conform into Roberts syndrome spectrum. Since the infant did not have the mutation associated with this disorder, this infant could be labeled as the first report of a pseudo-Roberts syndrome because many of his phenotypic anomalies are characteristic of Roberts syndrome in absence of the ESCO2 gene mutation.

Craniofacial phenotypes associated with Robinow syndrome.

Robinow syndrome is characterized by mesomelic limb shortening, hemivertebrae, and genital hypoplasia. Due to low prevalence and considerable phenotypic variability, it has been challenging to definitively characterize features of Robinow syndrome. While craniofacial abnormalities associated with Robinow syndrome have been broadly described, there is a lack of detailed descriptions of genotype-specific phenotypic craniofacial features. Patients with Robinow syndrome were invited for a multidisciplinary evaluation conducted by specialist physicians at our institution. A focused assessment of the craniofacial manifestations was performed by a single expert examiner using clinical examination and standard photographic images. A total of 13 patients with clinical and molecular diagnoses consistent with either dominant Robinow syndrome (DRS) or recessive Robinow syndrome (RRS) were evaluated. On craniofacial examination, gingival hyperplasia was nearly ubiquitous in all patients. Orbital hypertelorism, a short nose with anteverted and flared nares, a triangular mouth with a long philtrum, cleft palate, macrocephaly, and frontal bossing were not observed in all individuals but affected individuals with both DRS and RRS. Other anomalies were more selective in their distribution in this patient cohort. We present a comprehensive analysis of the craniofacial findings in patients with Robinow Syndrome, describing associated morphological features and correlating phenotypic manifestations to underlying genotype in a manner relevant for early recognition and focused evaluation of these patients.

Roberts syndrome in an Indian patient with humeroradial synostosis, congenital elbow contractures and a novel homozygous splice variant in ESCO2.

Roberts syndrome (also known as Roberts-SC phocomelia syndrome) is an autosomal recessive developmental disorder, characterized by pre- and postnatal growth retardation, limb malformations including bilateral symmetric tetraphocomelia or mesomelia, and craniofacial dysmorphism. Biallelic loss-of-function variants in ESCO2, which codes for establishment of sister chromatid cohesion N-acetyltransferase 2, cause Roberts syndrome. Phenotypic spectrum among patients is broad, challenging clinical diagnosis in mildly affected individuals. Here we report a 3-year-old boy with a mild phenotype of Roberts syndrome with bilateral elbow contractures, humeroradial synostosis, mild lower limb disparity, and facial dysmorphism. Trio whole-exome sequencing identified the novel biallelic splice variant c.1673+1G>A in ESCO2 in the patient. Aberrant ESCO2 pre-mRNA splicing, reduced relative ESCO2 mRNA amount, and characteristic cytogenetic defects, such as premature centromere separation, heterochromatin repulsion, and chromosome breaks, in patient cells strongly supported pathogenicity of the ESCO2 variant affecting one of the highly conserved guanine-thymine dinucleotide of the donor splice site. Our case highlights the difficulty in establishing a clinical diagnosis in individuals with minor clinical features of Roberts syndrome and normal intellectual and social development. However, next-generation sequencing tools allow for molecular diagnosis in cases presenting with mild developmental defects.

Treating Craniofacial Dysostoses with Hypertelorism by Monobloc Facial Bipartition Distraction: Surgical and Educational Videos.

Simultaneously advancing and medializing the orbital segments in a stable bone bloc constitutes a major advancement in craniofacial surgery. Monobloc bipartition enables destigmatization of the syndromic face by correcting the abnormal orbital axis and interorbital distance. The authors stratified this complex surgical approach into five major steps to facilitate a holistic understanding of the surgical sequence. The rationale for latency and activation periods and the advantages and disadvantages of this technique are described.

Neuropsychological Findings in Hamamy Syndrome: A Clinical Case Report.

This study, reports for the first time, the neuropsychological profile of a child with Hamamy syndrome-a rare genetic disorder with only five published cases (Buget, Canbolat, Akgul, & Kucukay, 2015). The patient was seen for a neuropsychological evaluation at ages 6 and 7, at the American University of Beirut Medical Center. Procedures included an extended clinical interview with the parent, behavioral observations, formal tests, and a series of parental rating scales. Patient was found to have relatively spared nonverbal intelligence, borderline-impaired language, and clinically impaired verbal reasoning, attention, and motor coordination. Additionally, he showed clinically significant concerns with behavioral regulation, metacognition, attention-deficit, and hyperactivity/impulsivity. The patient was diagnosed with a DSM-V Language Disorder, Speech Sound Disorder, and Attention Deficit/Hyperactivity Disorder, combined presentation, in the context of low-average intelligence. At follow-up, the neuropsychological profile was consistent, albeit improvement was noted following pharmacotherapy. This is the first published report that describes the neuropsychological functions of Hamamy syndrome. We make recommendations for early identification of cognitive strengths and weaknesses, and interventions to address them. Future research should evaluate additional functions such as memory and social/emotional development. (JINS, 2019, 25, 336-342).

Biopsy-proven multiple sclerosis in an adult patient with atypical craniometaphyseal dysplasia.

Craniometaphyseal dysplasia (CMD) is a rare condition characterised by progressive, diffuse hyperostosis of cranial and long bones, with compression of cranial nerves, linked to mutations in ANKH or GJA1 genes. Here we describe an adult case with clinical features of CMD, who developed cerebral expansive lesion of undetermined nature. Brain biopsy revealed active demyelinating lesions, consistent with multiple sclerosis. The genetic screening of target genes for CMD (ANKH and GJA1) resulted negative in this patient. The peculiar clinical association and the negativity of genetic analyses allow to hypothesise that other genetic causes, not already known, are responsible for the combination of these pathological conditions. Future studies aim to identify the genetic causes of CMD, which will be important to further understand the pathogenetic mechanism of this rare and invalidating disease.

Surgical approach of hypertelorbitism in craniofrontonasal dysplasia. / Abordagem cirúrgica do hiperteleorbitismo na displasia craniofrontonasal.

OBJECTIVE: to present our experience in the hypertelorbitism surgical treatment in craniofrontonasal dysplasia. METHODS: retrospective analysis of craniofrontonasal dysplasia patients operated through orbital box osteotomy or facial bipartition between 1997 and 2015. Surgical data was obtained from medical records, complementary tests, photographs, and clinical interviews. Surgical results were classified based on the need for additional surgery and orbital relapse was calculated. RESULTS: seven female patients were included, of whom three (42.86%) underwent orbital box osteotomy and four (57.14%) underwent facial bipartition. There was orbital relapse in average of 3.71±3,73mm. Surgical result according to the need for further surgery was 2.43±0.53. CONCLUSION: surgical approach to hypertelorbitism in craniofrontonasal dysplasia should be individualized, respecting the age at surgery and preferences of patients, parents, and surgeons.

OBJETIVO: apresentar nossa experiência no tratamento cirúrgico do hiperteleorbitismo na displasia craniofrontonasal. MÉTODOS: análise retrospectiva dos pacientes com displasia craniofrontonasal operados por orbital box osteotomy ou por bipartição facial entre os anos de 1997 e 2015. Informações sobre as intervenções cirúrgicas foram obtidas dos prontuários médicos, exames complementares, fotografias e entrevistas clínicas. Os resultados cirúrgicos foram classificados com base na necessidade de cirurgia adicional, e a recidiva orbital foi calculada. RESULTADOS: sete pacientes do sexo feminino foram incluídas, três submetidas à orbital box osteotomy (42,86%) e quatro (57,14%) à bipartição facial. Houve uma recidiva orbital média de 3,71±3,73mm. A média global dos resultados cirúrgicos de acordo com a necessidade de novas cirurgias foi de 2,43±0,53. CONCLUSÃO: a abordagem cirúrgica do hiperteleorbitismo na displasia craniofrontonasal deve ser individualizada, respeitando, sempre que possível, a idade e as preferências dos pacientes, seus familiares e cirurgiões.

Síndrome de Alagille; una patología que tener en cuenta / Alagille syndrome. A pathology to be considered

El síndrome de Alagille es una patología poco frecuente. Afecta a uno de cada 100 000 recién nacidos vivos. Se caracteriza por una hipoplasia de vías biliares que se asocia a otras malformaciones. Se presenta el caso de un niño chino de cuatro años al que se le diagnosticó esta patología tras ser adoptado a los 11 meses de edad (AU)

Alagille syndrome is an uncommon pathology. It is found in 1/100,000 live births. It is characterized by biliary duct hypoplasia associated with other malformations. We report the case of a four-year-old Chinese child who was diagnosed with this pathology after being adopted at 11 months of age (AU)

Abordagem cirúrgica do hiperteleorbitismo na displasia craniofrontonasal / Surgical approach of hypertelorbitism in craniofrontonasal dysplasia

RESUMO Objetivo: apresentar nossa experiência no tratamento cirúrgico do hiperteleorbitismo na displasia craniofrontonasal. Métodos: análise retrospectiva dos pacientes com displasia craniofrontonasal operados por orbital box osteotomy ou por bipartição facial entre os anos de 1997 e 2015. Informações sobre as intervenções cirúrgicas foram obtidas dos prontuários médicos, exames complementares, fotografias e entrevistas clínicas. Os resultados cirúrgicos foram classificados com base na necessidade de cirurgia adicional, e a recidiva orbital foi calculada. Resultados: sete pacientes do sexo feminino foram incluídas, três submetidas à orbital box osteotomy (42,86%) e quatro (57,14%) à bipartição facial. Houve uma recidiva orbital média de 3,71±3,73mm. A média global dos resultados cirúrgicos de acordo com a necessidade de novas cirurgias foi de 2,43±0,53. Conclusão: a abordagem cirúrgica do hiperteleorbitismo na displasia craniofrontonasal deve ser individualizada, respeitando, sempre que possível, a idade e as preferências dos pacientes, seus familiares e cirurgiões.

ABSTRACT Objective: to present our experience in the hypertelorbitism surgical treatment in craniofrontonasal dysplasia. Methods: retrospective analysis of craniofrontonasal dysplasia patients operated through orbital box osteotomy or facial bipartition between 1997 and 2015. Surgical data was obtained from medical records, complementary tests, photographs, and clinical interviews. Surgical results were classified based on the need for additional surgery and orbital relapse was calculated. Results: seven female patients were included, of whom three (42.86%) underwent orbital box osteotomy and four (57.14%) underwent facial bipartition. There was orbital relapse in average of 3.71±3,73mm. Surgical result according to the need for further surgery was 2.43±0.53. Conclusion: surgical approach to hypertelorbitism in craniofrontonasal dysplasia should be individualized, respecting the age at surgery and preferences of patients, parents, and surgeons.

Cranium Bifidum Occultum Associated with Hypertelorism Treated with Posterior Vault Reconstruction and Orbital Box Osteotomies: Case Report and Technical Note.

Cranium bifidum occultum is a disorder of skull ossification presenting as an enlarged posterior fontanelle in the upper posterior angle of the parietal bone near the intersection of the sagittal and lambdoid sutures. The standard treatment for cranium bifidum occultum is observation. We present a case of a 5-year-old boy who presented with a 15 × 4.5 cm midline posterior cranial vault defect consistent with diagnosis of cranium bifidum occultum associated with orbital hypertelorism and a widened nose. The patient underwent posterior vault reconstruction for correction of cranium bifidum occultum defect followed by bifrontal craniotomy and orbital box osteotomies for correction of orbital hypertelorism and nasal deformity. To our knowledge, this is the first reported case describing surgical treatment for cranium bifidum occultum associated with orbital hypertelorism.

Afectación cardiovascular en el síndrome de Loeys-Dietz / Cardiovascular involvement in Loeys-Dietz syndrome

No disponible

Hypertelorism and Orofacial Clefting Revisited: An Anthropometric Investigation.

OBJECTIVE: Since the 1960s, multiple studies have reported a tendency toward hypertelorism in individuals with nonsyndromic orofacial clefts (OFCs). However, the association between specific cleft types and increased interorbital distance has been inconsistent. Using three-dimensional (3D) surface imaging, we tested whether different forms of clefting showed evidence of increased interorbital distance. METHODS: Intercanthal and outercanthal distances and intercanthal indices were calculated from 3D facial surface images of 287 individuals with repaired OFCs. Raw measurements were converted to sex and age-normalized Z-scores. Mean Z-scores for individuals with cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP) were compared with reference normative values (controls) and one another directly using t tests and analysis of variance. RESULTS: The CLP group showed a significant increase in intercanthal width (P = .001) and intercanthal index (P < .001) compared with reference norms. The CP group showed a significant decrease (P < .001) in outercanthal width. The CL group showed no difference from reference norms. The proportion of clinically hyperteloric individuals was generally low but highest in the CLP group (7.4%). Cleft severity had little effect on interorbital spacing. CONCLUSIONS: Individuals with CLP exhibited on average a tendency toward mild hypertelorism, driven primarily by an increase in intercanthal distance. This tendency was not seen in CL or CP.

Dental treatment of a patient with Opitz G/BBB syndrome.

Opitz G/BBB syndrome is a genetic condition characterized by several abnormalities along the midline of the body, such as hypertelorism, craniofacial deformities, and dysphagia. This study reports the clinical features of Optiz syndrome and its importance in the knowledge of patients who are developmentally challenged as a whole, in order to establish adequate dental treatment for a certain clinical case. A 19-year-old patient visited the Paulista University for a dental treatment. The extraoral examination revealed ocular hypertelorism (wide-spaced eyes), oblique eyelids, epicanthus, low-set cart, and intellectual disability. During the intraoral examination, large caries lesions were observed surrounding the braces of the fixed orthodontic appliance and poor oral hygiene. Preventive and restorative treatments were carried out. It was concluded that the knowledge of patients with special needs as a whole is mandatory for an adequate dental treatment. This is a case report that highlights the importance of dentist and interdisciplinary care attendance for all patient systems, the examination and analyses should not be restricted to the oral cavity.

Craniometaphyseal dysplasia with obvious biochemical abnormality and rickets-like features.

BACKGROUND: Craniometaphyseal dysplasia (CMD) is a rare genetic disorder that is characterized by progressive sclerosis of the craniofacial bones and metaphyseal widening of long bones, and biochemical indexes were mostly normal. To further the understanding of the disease from a biochemical perspective, we reported a CMD case with obviously abnormal biochemical indexes. CASE REPORT: A 1-year-old boy was referred to our clinic. Biochemical test showed obviously increased alkaline phosphatase (ALP) and parathyroid hormone (PTH), mild hypocalcemia and hypophosphatemia. Moreover, significant elevated receptor activator of nuclear factor kappa-B ligand (RANKL) level, but normal ß-C-terminal telopeptide of type I collagen (ß-CTX) concentration were revealed. He was initially suspected of rickets, because the radiological examination also showed broadened epiphysis in his long bones. Supplementation with calcium and calcitriol alleviated biochemical abnormality. However, the patient gradually developed osteosclerosis which was inconformity with rickets. Considering that he was also presented with facial paralysis and nasal obstruction symptom, the diagnosis of craniometaphyseal dysplasia was suspected, and then was confirmed by the mutation analysis of ANKH of the proband and his family, which showed a de novo heterozygous mutation (C1124-1126delCCT) on exon 9. CONCLUSIONS: Our study revealed that obvious biochemical abnormality and rickets-like features might present as uncommon characteristics in CMD patients, and the calcium and calcitriol supplementation could alleviate biochemical abnormalities. Furthermore, although early osteoclast differentiation factor was excited in CMD patient, activity of osteoclast was still inert.

INTERMITTENT EXOTROPIA COURSE IN FRONTONASAL DYSPLASIA AND SEVERE ORBITAL HYPERTELORISM: CASE REPORT.

INTRODUCTION: Frontonasal dysplasia is a rare condition of congenital structure malformations of the midface. Ophthalmologic abnormalities have been estimated to occur in 87% of cases of frontonasal dysplasia. CASE REPORT: We report a case of type I frontonsal dysplasia in a 15-year old boy after the correction of severe hypertelorism, median nasal cleft w~ith a broad nasal root and associated decompensated intermittent exotropia with overaction. of the inferior oblique muscles and V pattern. He underwent bilateral lateral rectus recessions of 6.0 mm for intermittent exotropia when he was six years old. The correction of hypertelorism was performed with orbital rotation surgery when he was thirteen years old. For some time after strabismus surgery, the ocular alignment improved, but it deteriorated gradually. The ocular alignment improved after the hipertelorismus correction; however, intermittent exotropia deteriorated gradually again six to seven months later. On the last ophthalmologic examination, he had the ocular alignment on the level of small angle exotropia and associated hypertropia and occasionally even.small angle esotropiaat near. There was bilateral overelevation in addiction and V pattern, which remained unchanged after extensive facial bones surgical procedures. CONCLUSION: The high incidence of ocular abnormalities, particularly exodeviations, indicates that the early assessment by an ophthalmologist should be a part of the initial evaluation of patients with frontonasal dysplasia to detect treatable visual or ocular problems.

The Gorlin-Goltz Syndrome: diagnosis of a case associated with heart disease and type 2 diabetes mellitus / Síndrome de Gorlin-Goltz: diagnóstico de um caso associado à cardiopatia e diabetes mellitus 2

The Gorlin-Goltz syndrome (GGS) is a hereditary, autosomal dominant condition, with high penetrance and variable expressivity, resulting from mutations in the genes PTCH1, PTCH2, or SUFU. The diagnosis is based on the presence of 2 major criteria or a major criterion associated with 2 minor criteria, including multiple basal cell carcinomas, keratocystic odontogenic tumor (KOT), and bifid rib. Other endocrine, neurological, ophthalmologic, genital, respiratory, and cardiovascular alterations are found in the literature, but with variable manifestations. This study reports the case of a patient diagnosed with GGS associated with diastolic congestive heart failure and type 2 diabetes mellitus, who underwent multiple treatments for components of the syndrome. More recently, the patient underwent decompression followed by cystic enucleation of two KOTs in the jaw, oral rehabilitation with removable prosthodontics, cardiological evaluation, and attempted clinical control of endocrine and cardiac problems.

A síndrome de Gorlin-Goltz (SGG) é uma condição hereditária, autossômica dominante, com alta penetrância e expressividade variável, decorrente de mutações nos genes PTCH1, PTCH2 ou SUFU. O diagnóstico é baseado na presença de dois critérios maiores ou um critério maior associado a dois critérios menores, dentre eles múltiplos carcinomas basocelulares, tumor odontogênico ceratocístico (TOC) e costela bífida. Outras alterações endócrinas, neurológicas, oftalmológicas, genitais, respiratórias e cardiovasculares são encontradas na literatura, porém com manifestações variáveis. O objetivo deste trabalho é relatar um caso clínico de uma paciente sistematicamente diagnosticada com SGG associada à insuficiência cardíaca congestiva diastólica e diabetes mellitus 2 submetida a tratamentos seriados das respectivas manifestações sindrômicas. Mais recentemente, à descompressão cística seguida da enucleação de dois TOC em mandíbula, reabilitação oral com prótese total removível, avaliação cardiológica e tentativa de controle clínico das alterações endócrinas e cardíacas.

Diagnóstico tardio de síndrome de DiGeorge em criança hipocalcêmica: relato de caso / Late diagnosis of DiGeorge syndrome in hypocalcemic child: case report

A Síndrome de DiGeorge (SDG) decorre de uma microdeleção 22q11.2, sendo considerada uma das microdeleções mais frequentes em humanos. Caracteriza-se por espectro fenotípico bastante amplo, incluindo dificuldade de aprendizado, fácies dismórfica, anomalias cardíacas, hipocalcemia, hipoparatireoidismo, fenda palatina, anomalias do timo, insuficiência imunológica e problemas de fala e alimentação. Contudo, nenhum achado é patognomônico ou mesmo obrigatório. Este relato de caso pretende chamar a atenção para essa síndrome como causa potencial de hipocalcemia e convulsões hipocalcêmicas mesmo após o período neonatal. Reporta-se a história clinico-laboratorial e manejo de um menino de 12 anos, diagnosticado aos sete com SDG em decorrência de facies típica e crise convulsiva hipocalcêmica. O paciente apresentava diagnóstico prévio de transtorno do déficit de atenção e hiperatividade, atraso no desenvolvimento neuropsicomotor e fácies suspeita (micrognatia, orelhas de implantação baixa, hipertelorismo, nariz angular). A hipocalcemia que deflagrou a crise convulsiva foi secundária ao hipoparatireoidismo, sendo tratado com carbonato de cálcio e calcitriol. Houve melhora clínica, porém se manteve hipocalcêmico, apesar de dose otimizada da medicação. O caso é atípico, já que o diagnóstico de SDG foi feito tardiamente, visto que a maioria dos casos é diagnosticada no período neonatal. Além disso, o quadro demonstra a variabilidade de achados clínicos que podem ser encontrados nessa síndrome e a importância de se investigar a SDG em pacientes que apresentem hipocalcemia, mesmo em idades mais avançadas. Salienta-se que o diagnostico tem relevância na implicação dos cuidados à saúde, devido aos riscos imunológicos e cardiológicos apresentados pelos pacientes portadores, devendo ser realizado o mais precocemente possível.(AU)

The DiGeorge Syndrome (DGS) stems from a 22q11.2 microdeletion and is considered one of the most frequent microdeletions in humans. It is characterized by very wide phenotypic spectrum, including learning disability, dysmorphicfacies, cardiac abnormalities, hypocalcemia, hypoparathyroidism, cleft palate, thymus abnormalities, immune impairment and speech and feeding problems. However, any finding is pathognomonic or even mandatory. This case report aims to draw attention to this syndrome as a potential cause of hypocalcemia and hypocalcemic seizures even after the neonatal period. Refers to clinical and laboratory history and management of a boy of 12, diagnosed at 07 with DGS due to typical facies and hypocalcemic seizure. The patient had a previous diagnosis of attention deficit hyperactivity disorder, developmental delay and suspected facies (micrognathia, low-set ears, hypertelorism, angular nose). Hypocalcemia that triggered the seizure was secondary to hypoparathyroidism, being treated with calcium carbon- ate and calcitriol. There was clinical improvement, but hypocalcemic remained despite optimal medication dose. The case is atypical, since the diagnosis DGS was made later, as the majority of cases are diagnosed in the neonatal period. In addition, the table shows the variability of clinical findings that can be found in this syndrome and the importance of investigating the DGS in patients who have hypocalcaemia, even at older ages. Please note that the diagnosis is relevant in the involvement of health care due to immunological and cardiac risks posed by patients and should be done as early as possible.(AU)

Turbinoplasty surgery for nasal obstruction in craniometaphyseal dysplasia: A case report and review of the literature.

Craniometaphyseal dysplasia is a rare genetic condition characterised by hyperostosis of the skull base and sclerosis of craniofacial bones. This can cause nasal obstruction. This paper presents the case of a 14-year old with craniometaphyseal dysplasia presenting with nasal obstruction successfully treated with turbinoplasty. A literature search was conducted using PUBMED and EMBASE. In conclusion, in cases of craniometaphyseal dysplasia with nasal obstruction conventional techniques such as submucosal diathermy and outfracturing of inferior turbinates may not be adequate. Bony turbinoplasties along the whole length of the inferior turbinate may be required.