Neurocristopathies: Enigmatic Appearances of Neural Crest Cell-derived Abnormalities.

The neural crest is an important transient structure that develops during embryogenesis in vertebrates. Neural crest cells are multipotent progenitor cells that migrate and develop into a diverse range of cells and tissues throughout the body. Although neural crest cells originate from the ectoderm, they can differentiate into mesodermal-type or endodermal-type cells and tissues. Some of these tissues include the peripheral, autonomic, and enteric nervous systems; chromaffin cells of the adrenal medulla; smooth muscles of the intracranial blood vessels; melanocytes of the skin; cartilage and bones of the face; and parafollicular cells of the thyroid gland. Neurocristopathies are a group of diseases caused by the abnormal generation, migration, or differentiation of neural crest cells. They often involve multiple organ systems in a single person, are often familial, and can be associated with the development of neoplasms. As understanding of the neural crest has advanced, many seemingly disparate diseases, such Treacher Collins syndrome, 22q11.2 deletion syndrome, Hirschsprung disease, neuroblastoma, neurocutaneous melanocytosis, and neurofibromatosis, have come to be recognized as neurocristopathies. Neurocristopathies can be divided into three main categories: dysgenetic malformations, neoplasms, and combined dysgenetic and neoplastic syndromes. In this article, neural crest development, as well as several associated dysgenetic, neoplastic, and combined neurocristopathies, are reviewed. Neurocristopathies often have clinical manifestations in multiple organ systems, and radiologists are positioned to have significant roles in the initial diagnosis of these disorders, evaluation of subclinical associated lesions, creation of treatment plans, and patient follow-up. Online supplemental material is available for this article. ©RSNA, 2019.

Goldenhar syndrome: a rare diagnosis with possible prenatal findings.

Goldenhar syndrome is a rare congenital disease associated with hemifacial hypoplasia as well as ear and ocular defects. Sometimes it is also associated with vertebral and other bone defects, cardiac malformations and central nervous system anomalies. Its aetiology is not yet clarified in the literature. We present a case of multiple malformations detected in the morphology ultrasound (at 22 weeks of gestation), namely absent nasal bones, micrognathia and absent left radius, among other defects. Genetic counselling, fetal brain MRI and cardiac sonography, which showed ventricular septal defect, were performed. 11 syndromes with poor fetal or neonatal prognosis were identified as possible diagnosis, using a genetic database and the couple asked for a medical termination of pregnancy. Postmortem examination has shown features consistent with Goldenhar syndrome.

Asociación sindromática: Poland, Goldenhar, Moebius, Klippel-Feil: presentación de un caso clínico / Poland, Goldenhar, Moebius, Klippel-Feil syndrome: a clinical case

Poland Syndrome is a congenital defect characterized by a unilateral absence of the clavicular and stem costal portion of the pectoral muscles associated to abnormalities of other muscles of the thoracic wall, ribs, breast and upper extremity. It is found in one of 20 to 32 thousand newborns. It is found sometimes associated to other syndromes, most often with Moebius Syndrome, and rarely with Goldenhar and Klippel-Feil. Due to the association, a common pathogenic cause has been postulated, that being an anomaly of vascularization during embryonic development. Clinical Case: A newborn male was seen who presented with Poland, Goldenhar, Moebius and Klippel-Feil Syndromes. Clinically, he presented left hemi facial microsomy, microtia, shortening and paralysis of the facial nerve; his neck was short and movement was limited due to C4-C5 fusion; agenesis of left pectorals, hypoplasia of left radius and hand. There were no known additional family cases, being thus, a sporadic syndromatic association.

Introducción: El síndrome de Poland es un defecto muscular congénito, heterogéneo, caracterizado por ausencia unilateral de las porciones clavicular y/o esternocostal del músculo pectoral mayor, que se puede asociar a compromiso de otros músculos de la pared torácica, costillas, mama y extremidad superior. Se presenta con una frecuencia entre 1/20 000 al/32 000 nacidos. El síndrome de Poland se presenta en algunas ocasiones asociado a otros síndromes, siendo clásica con el síndrome de Moebius. Excepcionalmente se ha descrito la aparición conjunta con otros síndromes como Goldenhar y Klippel-Feil. Por la relación que existe entre ellos se plantea una patogenia común: anomalía en la vascularización, durante el desarrollo embrionario. Caso Clínico: Paciente de sexo masculino, con asociación sindromática de Poland, Goldenhar, Moebius y Klippel-Feil. Como características clínicas presenta a izquierda microsomia hemifacial, microtia, acortamiento de rama mandibular y parálisis facial; cuello corto y limitación de movimientos por fusión de C4-C5; agenesia del pectoral mayor izquierdo, hipoplasia de radio y mano izquierda. Sin antecedentes familiares, se trataría de un caso esporádico de asociación sindromática.

Hemifacial microsomia: from gestation to childhood.

Hemifacial microsomia (HFM) is a variable, complex malformation involving asymmetric hypoplasia of the face and ear. Little is known about the risk factors for or consequences of HFM. In this study, we describe 3 studies that have been or are currently being conducted to further our understanding of this malformation. The first completed study examined whether HFM risk is related to maternal exposures that may affect blood flow. In that case-control study, interview data from 230 mothers of children in the case group and 678 mothers of children in the control group suggested that maternal use of vasoactive medications in the first trimester, particularly in combination with cigarette smoking, was associated with increased risks of HFM. The second study is currently underway, in which we are evaluating whether HFM risk is related to genetic variation in pathways associated with vasculogenesis and hemostasis, using DNA collected in the first study. The third ongoing study observes children with HFM to identify psychosocial, cognitive, dental, and medical sequelae. When the children from the original case-control study are 6 or 7 years of age, mothers and teachers complete self-administered questionnaires that cover a wide range of psychosocial development domains. Preliminary analyses of 115 case and 314 control children suggest that children with HFM may have worse teacher-reported academic performance and possibly higher levels of internalizing behavior problems than control children. When data on the full study sample are available, further analyses will determine whether the preliminary findings remain and if they vary by HFM phenotype, parenting style, or indicators of social risk.

Congenital deformities and developmental abnormalities of the mandibular condyle in the temporomandibular joint.

The temporomandibular joint (TMJ) consists of the mandibular condyle and the articular eminence of the temporal bone. The morphological development of the TMJ during prenatal life lags behind other joints in terms of both the timing of its appearance and its progress. At birth, the joint is still largely underdeveloped. There are many causes of the various growth disturbances and abnormalities of the mandibular condyle and related structures. Growth disturbances in the development of the mandibular condyle may occur in utero late in the first trimester and may result in disorders such as aplasia or hypoplasia of the mandibular condyle. Meanwhile, hyperplasia of the mandibular condyle is not visible at birth and seems to be gradually acquired during growth. In the present review article, the congenital abnormalities of the mandibular condyle are classified morphologically into three major groups and two subgroups from a clinical standpoint: (1) hypoplasia or aplasia of the mandibular condyle, including (i) primary condylar aplasia and hypoplasia, (ii) secondary condylar hypoplasia; (2) hyperplasia; and (3) bifidity. In addition, the molecular-based etiology of anomalies of the mandibular condyle is also discussed.

Clinical-embryological and radiological correlations of oculo-auriculo-vertebral spectrum using 3D-CT.

OBJECTIVES: The purpose of this paper is to present a variety of imaging findings of oculo-auriculo-vertebral spectrum (Goldenhar syndrome) using three-dimensional reconstructed images from computed tomography (3D-CT), associating clinical and embryological patterns of the syndrome. METHODS: The study population consisted of 10 patients with oculo-auriculo-vertebral spectrum with clinically identified hemifacial microsomia. The patients were examined using spiral CT, and abnormal imaging features were grouped under facial, ear and temporal bone, vertebral, and skull base anomalies. The original CT data were transferred to a networked computer workstation with a computer graphics system to generate 3D-CT volume rendered images of the skull and vertebra. Two observers analysed the bone and muscular setting protocols to assess the relationship between bone and muscular structures. RESULTS: Asymmetric underdevelopment was a characteristic pattern of this syndrome resulting from hypoplasia of the mandibular ramus and condyle, the zygomatic, sphenoid and auricular conduct bones, and the temporal and masseter muscles. The syndrome was associated with local atrophy seen on 3D-CT images using specific bone and muscles protocols in all cases. CONCLUSIONS: Understanding the aetiology, embryology and wide imaging spectrum of this syndrome is essential to make a correct diagnosis, for treatment planning, and for evaluation when associated with a 3D-CT computer graphics system.

Goldenhar's syndrome: case report.

A case of Goldenhar's Syndrome (oculoauriculovertebral dysplasia) in a 3-day-old Nigerian neonate with right anophthalmos and lipodermoid, left limbal dermoid, bilateral preauricular appendages and mandibular hypoplasia is presented. The lipodermoid was attached to the tarsal conjunctiva of the lower lid of the anophthalmic side. The causative factor was presumably maternal drug (traditional medicine) ingestion at three months gestation. No similar case has been reported previously. The literature on Goldenhar's Syndrome is briefly reviewed.

A theory on the embryogenesis of oculo-auriculo-vertebral (Goldenhar) syndrome.

Oculo-auriculo-vertebral (OAV) syndrome is made up of anomalies, mainly of first and second branchial arch derivatives. Characteristic features include structural malformations of the external and middle ears, face, and jaw. It has been previously suggested that hemorrhage involving the first and second branchial arches causes hypoplasia and malformation of the face and auricle, but this theory cannot explain the multisystemic and protean manifestations of this disease. The theory set forth describes the cutaneous, facial, vertebral, and systemic anomalies in the OAV spectrum as a result of ectodermal nondisjunction early in development with subsequent mesodermal tethering. A subgroup of OAV may therefore be a disorder of ectodermal nondisjunction involving the otic placode similar to the spectrum of diseases such as occult spinal dysraphism that is associated with the same mechanism in the embryonic neuraxis. This would imply a molecular mechanism involving cell adhesion molecules that unify the two disease processes and explain the multisystem anomalies of the OAV syndrome.

OEIS complex with craniofacial anomalies--defect of blastogenesis?

We report on a 31-week fetus with hydrocephalus, hypertelorism, microtia, short neck, vertebral and rib defects, scoliosis, omphalocele, exstrophy of bladder, absent external genitalia and pubic rami, imperforate anus, diaphragmatic hernia, defective lobulation of lungs, single kidney, bicornuate uterus, and flexion deformities of the limbs. Similar extensive anomalies in the rostral and caudal regions were described by Russell et al. [Pediatrics, 67:176-182, 1981] and Stewart et al. [Am J Med Genet, 45:426-429, 1993]. The patients described by them had a combination of the oculo-auriculo-vertebral sequence (OAV) and caudal deficiency sequence, whereas the patient reported here can best be described as a combination of OAV and OEIS (omphalocele, exstrophy of bladder, imperforate anus, spinal defects) complexes. The widespread malformations seen in our patient may be the result of an error during blastogenesis.

Severe axial anomalies in the oculo-auriculo-vertebral (Goldenhar) complex.

We have studied 4 infants with oculo-auriculo-vertebral (OAV) complex or Goldenhar "syndrome" who also had severe axial anomalies, including multiple vertebral segmentation errors affecting the thoracic and the lumbar spine. One of them presented a previously unreported pattern of vertebral and rib anomalies similar to spondylocostal dysostosis. Three patients had twins, and all 4 patients had other associated non-skeletal malformations which affected the midline, i.e., cleft lip and palate, esophageal atresia with tracheoesophageal fistula, and ventricular septal defect. The broad extent of the axial anomalies, the association with midline defects and twinning, and the combination in the same patient of two distinct conditions support the concept that OAV complex is a polytopic developmental field defect arising during blastogenesis.

A patient with median cleft face anomaly and bilateral Goldenhar anomaly.

We describe a girl with a median cleft face anomaly and oculoauriculovertebral "dysplasia" (bilateral Goldenhar anomaly). The facial anomalies in this child are thought to be due to malfusion of neural crest cells of midline, lateral, and oblique facial processes. Disturbances of these migrating waves of neural crest cells may result in maldevelopment of the intercanthal area, nose, lip, palate, lower eyelid, and lateral aspect of mouth and ear. Except for cleft palate, all of these anomalies are present in this case. The child might have a new "syndrome" which we propose be called oculoauriculofrontonasal anomaly.

Role of the neural crest in anterior segment development and disease.

Certain eye and associated systemic developmental anomalies are apparently related by virture of a common neural crest origin. The development of the anterior segment is extremely complex and is dependent upon the presence or absence of certain local factors (including extracellular matrices and glycoproteins), inductors, receptors, and specific time sequencing. Understanding anterior segment anomalies and their systemic associations requires an understanding of neural crest proliferation and migration patterns; and they may be unified under the designation of neurocristopathies. Goldenhar's syndrome, not previously considered a neurocristopathy, may be considered one on the basis of the relationship between clinical findings and neural crest embryology.

Cranial defects in the Goldenhar syndrome.

Four patients are presented with the Goldenhar syndrome (GS) and cranial defects consisting of plagiocephaly, microcephaly, skull defects, or intracranial dermoid cysts. Twelve cases from the literature add hydrocephalus, encephalocele, and arhinencephaly to a growing list of brain anomalies in GS. As a group, these patients emphasize the variability of GS and the increased risk for developmental retardation with multiple, severe, or unusual manifestations. The temporal relation of proposed teratogenic events in GS provides an opportunity to reconstruct biological relationships within the 3-5-week human embryo.