Shah-Waardenburg Syndrome Research Articles

Hirschsprung disease.

Hirschsprung disease (HSCR) is a rare congenital intestinal disease that occurs in 1 in 5,000 live births. HSCR is characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the intestine. Most patients present during the neonatal period with the first meconium passage delayed beyond 24 h, abdominal distension and vomiting. Syndromes associated with HSCR include trisomy 21, Mowat-Wilson syndrome, congenital central hypoventilation syndrome, Shah-Waardenburg syndrome and cartilage-hair hypoplasia. Multiple putative genes are involved in familial and isolated HSCR, of which the most common are the RET proto-oncogene and EDNRB. Diagnosis consists of visualization of a transition zone on contrast enema and confirmation via rectal biopsy. HSCR is typically managed by surgical removal of the aganglionic bowel and reconstruction of the intestinal tract by connecting the normally innervated bowel down to the anus while preserving normal sphincter function. Several procedures, namely Swenson, Soave and Duhamel procedures, can be undertaken and may include a laparoscopically assisted approach. Short-term and long-term comorbidities include persistent obstructive symptoms, enterocolitis and soiling. Continued research and innovation to better understand disease mechanisms holds promise for developing novel techniques for diagnosis and therapy, and improving outcomes inpatients.

Waardenburg-Shah syndrome rare and challenging case report from Somalia.

Introduction and importanceWaardenburg-Shah disorder could be an uncommon autosomal recessive inherited ailment characterized by aganglionic megacolon with a high mortality rate. Babies born with Waardenburg syndrome may have typical features of hair, skin and eye pigmentary abnormalities, and hearing loss. Here we present a case with typical presentation of Waardenburg Shah syndrome.Case presentationThis is a case of neonatal intestinal obstruction caused by a rare syndrome known as Waardenburg-Shah syndrome, with clinical manifestations of abdominal distension, bilious vomiting, and a history of delayed meconium passage with a family history of variant forms of this syndrome. The patients underwent first laparotomy, which found no atresia.post op colongarphy revealed a narrowed colon. Then reoperated, and a biopsy was taken and opened ileostomy. The pathology result showed gangilion negative. The patient was lost due to uncontrollable sepsis at the age of 2 months.Clinical discussionWaardenurg syndrome is a congenital audito-pigmentary syndrome first described in 1951.Waardenurg syndrome is classified into four types, WS1 to WS4, and they share the common presence of congenital sensoneural hearing loss and pigmentary defects. The diagnosis of WS has major and minor criteria. The definitive management of this disorder involves surgical removal of aganglionic segment of the bowel and connecting functioning gangilioic bowel to the anus.ConclusionShah-Waardenburg syndrome TYPE-4 is a relatively unusual syndrome characterized by a higher prevalence of whole colonic aganglionosis with or without small bowel involvement, resulting in substantial morbidity and mortality in the neonatal age range.

Endothelin-3 gene mutations in isolated and syndromic Hirschsprung disease.

Hirschsprung disease (HSCR, aganglionic megacolon) is a frequent congenital malformation regarded as a multigenic neurocristopathy. Four susceptibility genes have recently been identified in HSCR, namely the RET proto-oncogene, the glial cell line-derived neurotrophic factor (GDNF), the endothelin B receptor (EDNRB) and the endothelin-3 genes (EDN3). Homozygosity for EDN3 mutations has been previously shown to cause the Shah-Waardenburg syndrome, a combination of HSCR with features of the Waardenburg syndrome. Here, we report on heterozygous EDN3 missense mutations in isolatec HSCR. The present data give further support to the role of the endothelin signaling pathway in the development of neural crest-derived enteric neurons. They also suggest the possibility that either recessive or weakly penetrant dominant alleles could occur at the EDN3 locus, depending on the nature of the mutation.

Shah-Waardenburg syndrome

Introduction: Shah-Waardenburg syndrome (SWS) is WS associated with Hirschsprung's disease. It is very rare with Aim: The aim of this study was to describe our experience with SWS. Methods: The records of patients admitted to our tertiary care pediatric surgical institute between 2011 and 2015 were retrospectively reviewed. All patients with histopathological diagnosis of Hirschsprung's disease were studied. SWS was identified as per the diagnostic criteria proposed by the Waardenburg consortium. Results: There were 202 patients diagnosed with Hirschsprung's disease during 5 years. We identified three male patients fulfilling the diagnostic criteria for WS (white forelock with the involvement of eyebrows and eyelashes, pigmentary disturbances of the iris, and broad high nasal root). All presented in the neonatal period with clinical and radiological features of small bowel obstruction. Family history (sibling) of SWS was seen in one of the neonates. Exploration revealed distended jejunal and ileal loops in all of them; colon contracted and unused (microcolon). Multiple seromuscular biopsies were performed from colon in all 3 neonates. Initial ileostomy was performed in case 2 and case 3. In case 1, the right transverse colostomy was done primarily as total colonic aganglionosis (TCA) was not expected (absence of transition zone in the early neonatal period) and also frozen section facilities were not available. It was followed by ileostomy (second surgery) about 15 cm proximal to the ileocecal junction as colostomy was not functioning adequately. The histopathology of gut biopsies revealed aganglionosis in the entire colon, confirming the diagnosis of TCA in all the cases. Out of three patients in our study, two neonates died in the postoperative period, while third case succumbed due to severe episodes of ileostomy diarrhea. Conclusion: A patient of WS presenting with neonatal intestinal obstruction or constipation since birth should be evaluated on the lines of SWS . Patients with SWS have a higher incidence of TCA or long-segment Hirschsprung's disease. In SWS when transition zone is not clear, an ileostomy would be preferable in view of nonavailability of frozen section.

Skip segment Hirschsprung's disease in a patient with Shah-Waardenburg Syndrome

Abstract Introduction We present a new case of Skip segment Hirschsprung's disease (SSHD) associated to Waardenburg's syndrome, in a patient with total colonic aganglionosis (TCA). Even though there are more than 30 cases reported in the literature, SSHD's existence is controversial, due to the fact that there is not clear embriological theory to explain this phenomenon. Case report 20 months-old male patient, that at four days-old had a temporary ileostomy because of an episode of intestinal obstruction. A microileum and right microcolon was observed at the moment of surgery. Biopsies of the ileum and microcolon confirmed the aganglionism. At four months-old definitive surgery was performed according to Boley's procedure. Hystopathological study of the surgical piece showed absence of ganglion cells in cecum and ascending colon (SSHD). The postoperatory has been favorable. A mutation in SOX10 gen was objectified in the molecular study, that confirmed the Shah Waardenburg syndrome. Discussion Most of cases of SSHD were observed in patients with TCA, as in our case. These patients usually need a temporary stoma before the definitive surgery. We think that the only way to discover SSHD cases is to make extended biopsies in left, transverse and right colon, and in ileum, while performing the ileostomy or in the definitve surgery. Conclusion SSHD must be included as a new phenotype in Hirschsprung spectrum. Preservation of these intestinal segments can improve intestinal function, specially in patients with TCA.

Shah-Waardenburg Syndrome: A Spectrum of Aganglionosis

Aim: To report our experience with four neonates with Shah-Waardenburg syndrome (SWS) and highlight the spectrum of intestinal aganglionosis in this disorder. Method: Four consecutive cases of SWS that were managed over last five years at two pediatric surgical centres are described. The syndrome was identified by virtue of its various components. Results: All four children (3 boys/1 girl) presented in the neonatal period with features of intestinal obstruction. All had the characteristic white forelock and skin depigmentation with blue/grey irides. Two children were diverted (right transverse colostomy and ileostomy respectively) which never functioned satisfactorily. They died due to septicemia before further procedures could be planned. One child underwent three laparotomies with progressively proximal stoma construction. Eventual jejunal biopsy was also aganglionic and guardians chose to terminate therapy. The fourth child underwent an ileostomy in the neonatal period for total colonic aganglionosis and later on, an ileal pull-through. He is thriving on follow-up of 4 years. Conclusions: The striking association of phenotypic features makes SWS a rare but highly recognizable syndrome. Evaluation for Hirschsprungs’ disease must be done in such children while keeping a high suspicion for the extended varieties.

Perils of total colonic aganglionosis presenting in neonatal age.

The purpose of this study is to review the cases of total colonic aganglionosis seen in the span of ten years at a pediatric surgery unit of a tertiary care public hospital in New Delhi. Medical records of twelve patients with total colonic aganglionosis were retrieved. Ten out of the twelve patients were males; seven were of the Muslim community. Average recorded birth weight was 2.2 kg. Ten patients presented with features of intestinal obstruction, while two presented with perforation peritonitis. Among the cases of obstruction, Hirschsprung's disease was suspected in eight cases (one was associated with Shah-Waardenburg syndrome), one case each was preoperatively diagnosed as ileal atresia and meconium ileus. Abdominal X-rays at presentation of all the neonates except in one with Shah-Waardenburg syndrome showed multiple air fluid levels. Contrast enema was done in five patients. It showed micro-colon in two patients, and typical question mark sign, dilated small bowel with transition zone in hepatic flexure and normal caliber colon in one each. All the patients underwent exploratory laparotomy. Intra-operatively, the transition zone was seen at distal ileum in ten cases and at hepatic flexure and transverse colon in one each. Biopsies of all the twelve patients eventually showed absence of ganglion cells in entire colon. Ileostomy was done in nine cases, colostomy in two and primary Kimura's procedure in one (this patient was discharged and lost to follow up). Left colonic patch with Swenson's pull through with ileostomy was done for one patient on colostomy. His stoma was closed; he was eventually discharged and lost to follow up. In the other patient with colostomy, the stoma was closed and an ileostomy was created. Of all the patients on ileostomy, three expired in the immediate postoperative period. Four were lost to follow up. Two underwent Kimura's procedure; and expired few months later. One patient on ileostomy is awaiting further treatment. The outcomes for total colonic aganglionosis in those presenting in neonatal age tend to be unsatisfactory in the developing countries.

Perils of Total Colonic Aganglionosis Presenting in Neonatal Age

Background: The purpose of this study is to review the cases of total colonic aganglionosis seen in the span of ten years at a pediatric surgery unit of a tertiary care public hospital in New Delhi.Methods: Medical records of eleven patients with total colonic aganglionosis were retrieved.Results: Ten out of the twelve patients were males; seven were of the Muslim community. Average recorded birth weight was 2.2 kg. Ten patients presented with features of intestinal obstruction, while two presented with perforation peritonitis. Among the cases of obstruction, Hirschsprung's disease was suspected in eight cases (one was associated with Shah-Waardenburg syndrome), one case each was preoperatively diagnosed as ileal atresia and meconium ileus. Abdominal X-rays at presentation of all the neonates except in one with Shah-Waardenburg syndrome showed multiple air fluid levels. Contrast enema was done in five patients. It showed micro-colon in two patients, and typical question mark sign, dilated small bowel with transition zone in hepatic flexure and normal caliber colon in one each. All the patients underwent exploratory laparotomy. Intra-operatively, the transition zone was seen at distal ileum in ten cases and at hepatic flexure and transverse colon in one each. Biopsies of all the twelve patients eventually showed absence of ganglion cells in entire colon. Ileostomy was done in nine cases, colostomy in two and primary Kimura's procedure in one (this patient was discharged and lost to follow up). Left colonic patch with Swenson’s pull through with ileostomy was done for one patient on colostomy. His stoma was closed; he was eventually discharged and lost to follow up. In the other patient with colostomy, the stoma was closed and an ileostomy was created. Of all the patients on ileostomy, three expired in the immediate postoperative period. Four were lost to follow up. Two underwent Kimura's procedure; and expired few months later. One patient on ileostomy is awaiting further treatment.Conclusion: Management of total colonic aganglionosis is still in its infancy in the developing world. There is a lot of scope for improvement in the management. There is a need to have a stringent follow up of patients in order to know the long-term outcomes of the disease.

Waardenburg syndrome type 4: Report of two new cases caused by SOX10 mutations in Spain

Shah-Waardenburg syndrome or Waardenburg syndrome type 4 (WS4) is a neurocristopathy characterized by the association of deafness, depigmentation and Hirschsprung disease. Three disease-causing genes have been identified so far for WS4: EDNRB, EDN3, and SOX10. SOX10 mutations, found in 45-55% of WS4 patients, are inherited in autosomal dominant way. In addition, mutations in SOX10 are also responsible for an extended syndrome involving peripheral and central neurological phenotypes, referred to as PCWH (peripheral demyelinating neuropathy, central dysmyelinating leucodystrophy, Waardenburg syndrome, Hirschsprung disease). Such mutations are mostly private, and a high intra- and inter-familial variability exists. In this report, we present a patient with WS4 and a second with PCWH due to SOX10 mutations supporting again the genetic and phenotypic heterogeneity of these syndromes. Interestingly, the WS4 family carries an insertion of 19 nucleotides in exon 5 of SOX10, which results in distinct phenotypes along three different generations: hypopigmentation in the maternal grandmother, hearing loss in the mother, and WS4 in the proband. Since mosaicism cannot explain the three different related-WS features observed in this family, we propose as the most plausible explanation the existence of additional molecular events, acting in an additive or multiplicative fashion, in genes or regulatory regions unidentified so far. On the other hand, the PCWH case was due to a de novo deletion in exon 5 of the gene. Efforts should be devoted to unravel the mechanisms underlying the intrafamilial phenotypic variability observed in the families affected, and to identify new genes responsible for the still unsolved WS4 cases.

Anesthetic management of Shah-Waardenburg syndrome: Experience of two cases and review of literature

Waardenburg syndrome (WS) is a rare autosomally inherited and genetically heterogeneous disorder of neural crest cell development. Literature regarding the anesthetic management of these cases is limited. We present 2 cases of Shah–Waardenburg syndrome and discuss them in the context of review of previously published cases.

A novel SOX10 mutation in a patient with PCWH who developed hypoxic–ischemic encephalopathy after E. coli sepsis

We describe a male infant with a novel SOX10 mutation and a severe course of PCWH--a special phenotype of Shah-Waardenburg syndrome involving peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung's disease. The patient had severe hypoplastic hypoganglionosis of the small and total colonic intestine together with peripheral and central dysmyelination. The patient was completely dependent on parenteral nutrition. We identified a novel frameshift mutation, p.Asp293GlyfsX10, in the SOX10 gene of this patient. The mutation would encode a protein that lacked the transactivation domain and resulted in the largest duplication described to date. At the age of 20 months, the boy presented with a severe complication with a translocation of Escherichia coli and developed sepsis leading to severe hypoxic-ischemic encephalopathy with persistent vegetative state (PVS). The boy died at the age of 24 months. Septic encephalopathy with hypoxic-ischemic encephalopathy can be a serious complication in severe sepsis. It is unknown to what extent the mutant SOX10 protein influenced the degree of brain injury--for example central nervous system susceptibility to hypoxia-during sepsis, which may explain the severe encephalopathy with clinical signs of PVS the boy developed.

Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease

Hirschsprung disease (HSCR) is a common, multigenic neurocristopathy characterized by incomplete innervation along a variable length of the gut. The pivotal gene in isolated HSCR cases, either sporadic or familial, is RET. HSCR also presents in various syndromes, including Shah-Waardenburg syndrome (WS), Down (DS), and Bardet-Biedl (BBS). Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays. Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease. We also demonstrate that these genes interact genetically in vivo to modulate gut innervation, and that this interaction likely occurs through complementary, yet independent, pathways that converge on the same biological process.

Association of Shah-Waardenburgh syndrome: a review of 6 cases

Shah-Waardenburg syndrome (SWS) is a neurocristopathy and is characterized by Hirschsprung's disease (HD), deafness, and depigmentation of hairs, skin, and iris. Objective The aim of the article is to study the relative frequency of associations in 6 consecutive cases of SWS. Methods A review of 6 consecutive patients with SWS was performed to study the frequency of various components of the syndrome. Results Six patients had features of SWS. All patients had HD; of these, 3 had rectosigmoid HD, whereas 3 had extended HD. All patients had white forelock of hairs with skin depigmentation. One patient had sensorineural deafness, whereas other babies were less than 1 year, and thus, full evaluation of hearing deficiency was not assessed. Three patients had blue eyes, whereas other babies had normal iris pigmentation. Skin depigmentation was noted in 5 of the 6 patients. Three babies were seriously malnourished and showed higher association of enterocolitis. Conclusion Shah-Waardenburg syndrome is an uncommon association of HD. Depigmentation with a white forelock and skin manifestations are common, whereas blue iris, long segment disease, and enterocolitis are present in nearly half of the patients.

Shah-Waardenburg syndrome

A case of Shah-Waardenburg syndrome, a rare variant of Waardenburg syndrome, is presented. Inherited as an autosomal recessive or dominant trait, the disorder presumably results from defective migration of neural crest cells. It clinically manifests with pigmentary anomalies and congenital megacolon.

Shah-Waardenburg syndrome and PCWH associated with SOX10 mutations: A case report and review of the literature

Shah-Waardenburg syndrome is a rare congenital disorder with variable clinical expression, characterised by aganglionosis of the rectosigmoïd (Hirschsprung disease), and abnormal melanocyte migration, resulting in pigmentary abnormalities and sensorineural deafness (Waardenburg syndrome). Mutations in the EDN, EDNRB and SOX10 genes can be found in patients with this syndrome. SOX10 mutations are specifically associated with a more severe phenotype called PCWH: peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease. Neuronal expression of SOX10 occurs in neural crest cells during early embryonic development and in glial cells of the peripheral and central nervous systems during late embryonic development and in adults. We present a 4-year-old girl with the PCWH phenotype associated with a de novo nonsense mutation (S384X) in SOX10. Main clinical features were mental retardation, peripheral neuropathy, deafness, Hirschsprung disease, distal arthrogryposis, white hairlock, and growth retardation. She presented with hypotonia, developmental delay, reduced peripheral nerve conduction velocities, and radiologically assessed central hypomyelination. Subsequently, the formation of abnormal myelin within the central and peripheral nervous system was functionally and radiologically assessed. Children presenting with features of Waardenburg syndrome and neurological dysfunction should be tested for mutations in the SOX10 gene to enable diagnosis and counselling.

Human Connexin 32, a gap junction protein altered in the X-linked form of Charcot-Marie-Tooth disease, is directly regulated by the transcription factor SOX10.

Mutations in SOX10, a transcription modulator crucial in the development of the enteric nervous system (ENS), melanocytes and glial cells, are found in Shah-Waardenburg syndrome (WS4), a neurocristopathy that associates intestinal aganglionosis, pigmentation defects and sensorineural deafness. Expression of MITF and RET, two genes that play important roles during melanocyte and ENS development, respectively, are controlled by SOX10. The observation that some WS4 patients present with myelination defects of the central and peripheral nervous systems correlates with the recent finding that P(0), a major component of the peripheral myelin, is another transcriptional target of SOX10. These phenotypic features suggest that SOX10 could regulate expression of other genes involved in the myelination process as well. Thus, we tested the ability of SOX10 to regulate expression of MBP, PMP22 and Connexin 32, three major proteins of the peripheral myelin. Our study shows that this factor, in synergy with EGR2, strongly activates Cx32 expression in vitro by directly binding to its promoter. In agreement with this finding, SOX10 and EGR2 mutants identified in patients with peripheral myelin defects fail to transactivate the Cx32 promoter. Moreover, we show that a mutation of the Cx32 promoter previously described in a patient with the X-linked form of Charcot-Marie-Tooth (CMTX) disease impairs SOX10 function. In addition to providing new insights into the molecular mechanisms underlying some of the peripheral myelin defects observed in CMTX disease, these results further extend the spectrum of genes that are regulated by SOX10.

Relationship between the type of RET/GDNF/NTN or SOX10 gene mutations and long-term results after surgery for total colonic aganglionosis with small bowel involvement

Background/Purpose: Germline mutations of the RET-mediated or SOX10-mediated signaling pathway genes have been reported in total colonic aganglionosis (TCA). The authors investigated the possible relationship between the type of such genomic abnormalities and surgical outcomes. Methods: Sixteen patients with TCA with extensive small bowel involvement were studied. DNA sequences of all the RET/GDNF/NTN and SOX10 coding regions were determined by the direct DyeDeoxy Terminator Cycle method. Data on the patients' clinical courses were obtained retrospectively from their medical charts and surgical records. Results:RET or SOX10 germline mutations were identified in 11 of the 16 patients (68.8%). In children with aganglionosis up to the jejunum or ileum, most grew up within normal ranges, and the frequency of bowel movements decreased to 2 to 4 times per day within 5 years. However, in 5 infants with total intestinal aganglionosis, only 2 survived beyond 2 years of age, both of whom underwent Ziegler's myectomy-myotomy. A SOX10 mutation was identified in an infant with Shah-Waardenburg's syndrome, and he showed persistent bowel malfunction. Conclusion: The existence or type of RET mutation usually did not affect surgical results in this series of TCA patients, whereas the mutational analysis suggested 2 disease categories of TCA showing different postoperative courses, which may reflect the disparate pathogenesis in the enteric nervous system development induced by impaired RET or SOX10 signaling pathway. J Pediatr Surg 36:1685-1688. Copyright © 2001 by W.B. Saunders Company.

EDNRB/EDN3 and Hirschsprung disease type II.

The study of vertebrate pigmentary anomalies has greatly improved our understanding of melanocyte biology. One such disorder, Waardenburg syndrome (WS), is a mendelian trait characterized by hypopigmentation and sensorineural deafness. It is commonly subdivided into four types (WS1-4), defined by the presence or absence of additional symptoms. WS type 4 (WS4), or Shah-Waardenburg syndrome, is also known as Hirschsprung disease Type II (HSCR II) and is characterized by an absence of epidermal melanocytes and enteric ganglia. Mutations in the genes encoding the endothelin type-B receptor (EDNRB) and its physiological ligand endothelin 3 (EDN3) are now known to account for the majority of HSCR II patients. Null mutations in the mouse genes Ednrb and Edn3 have identified a key role for this pathway in the normal development of melanocytes and other neural crest-derived lineages. The pleiotropic effects of genes in this pathway, on melanocyte and enteric neuron development, have been clarified by the embryologic identification of their common neural crest (NC) ancestry. EDNRB and EDN3 are transiently expressed in crest-derived melanoblast and neuroblast precursors, and in the surrounding mesenchymal cells, respectively. The influence of EDNRB-mediated signaling on the emigration, migration, proliferation, and differentiation of melanocyte and enteric neuron precursors, in vivo and in vitro has recently been the subject of great scrutiny. A major emergent theme is that EDN3-induced signaling prevents the premature differentiation of melanocyte and enteric nervous system precursors and is essential between 10 and 12.5 days post-coitum. We review the present understanding of pigment cell development in the context of EDNRB/EDN3--a receptor-mediated pathway with pleiotropic effects.

Neurological Phenotype in Waardenburg Syndrome Type 4 Correlates with Novel SOX10 Truncating Mutations and Expression in Developing Brain

Waardenburg syndrome type 4 (WS4), also called Shah-Waardenburg syndrome, is a rare neurocristopathy that results from the absence of melanocytes and intrinsic ganglion cells of the terminal hindgut. WS4 is inherited as an autosomal recessive trait attributable to EDN3 or EDNRB mutations. It is inherited as an autosomal dominant condition when SOX10 mutations are involved. We report on three unrelated WS4 patients with growth retardation and an as-yet-unreported neurological phenotype with impairment of both the central and autonomous nervous systems and occasionally neonatal hypotonia and arthrogryposis. Each of the three patients was heterozygous for a SOX10 truncating mutation (Y313X in two patients and S251X [corrected] in one patient). The extended spectrum of the WS4 phenotype is relevant to the brain expression of SOX10 during human embryonic and fetal development. Indeed, the expression of SOX10 in human embryo was not restricted to neural-crest-derived cells but also involved fetal brain cells, most likely of glial origin. These data emphasize the important role of SOX10 in early development of both neural-crest-derived tissues, namely melanocytes, autonomic and enteric nervous systems, and glial cells of the central nervous system.

Expression of the SOX10 gene during human development

SOX10, a new member of the SOX gene family, is a transcription factor defective in the Dom ( Dominant megacolon) mouse and in the human Shah-Waardenburg syndrome. To help unravel its physiological role during human development, we studied SOX10 gene expression in embryonic, fetal, and adult human tissues by Northern blot and in situ hybridization. As in mice, the human SOX10 gene was essentially expressed in the neural crest derivatives that contribute to the formation of the peripheral nervous system, and in the adult central nervous system. Nevertheless, it was more widely expressed in humans than in rodents. The spatial and temporal pattern of SOX10 expression supports an important function in neural crest development.