Anne V Hing

Seattle Children's Hospital, Seattle, Washington, United States

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Publications (54)189.5 Total impact

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    ABSTRACT: The craniofacial skeleton is made up of the neurocranium, which encases the brain, and the viscerocranium, which includes the bones of the face and cranial base. At birth, the human craniofacial skeleton is comprised of 44 bones that develop via both endochondral and intramembranous ossification, depending on the bone. Undifferentiated mesenchyme separates the bones for varying periods of postnatal life, playing a key role in regulating cranioskeletal growth. Appositional bone growth at the suture margins is regulated by a complex crosstalk between growth factor signaling pathways, some of which function more prominently in specific sutures. In this chapter, we review the embryology and current understanding of the molecular genetic basis of premature fusions (synostosis) of both the calvarial and facial sutures gleaned from genetic studies in humans and model organisms such as the mouse. In addition, we reassess the spectrum of mutations found in FGFR2, the most prominent factor implicated in craniofacial synostosis, and propose a new model for explaining the impact of many of the common amino acid substitutions that result in pathology. Finally, advancements that promise to enable use of mesenchymal stem cells in tissue engineering-based approaches are discussed with respect to prospects for more effective treatment of these craniofacial conditions.
    No preview · Chapter · Jan 2015
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    ABSTRACT: Mutations in components of the major spliceosome have been described in disorders with craniofacial anomalies, e.g., Nager syndrome and mandibulofacial dysostosis type Guion-Almeida. The U5 spliceosomal complex of eight highly conserved proteins is critical for pre-mRNA splicing. We identified biallelic mutations in TXNL4A, a member of this complex, in individuals with Burn-McKeown syndrome (BMKS). This rare condition is characterized by bilateral choanal atresia, hearing loss, cleft lip and/or palate, and other craniofacial dysmorphisms. Mutations were found in 9 of 11 affected families. In 8 families, affected individuals carried a rare loss-of-function mutation (nonsense, frameshift, or microdeletion) on one allele and a low-frequency 34 bp deletion (allele frequency 0.76%) in the core promoter region on the other allele. In a single highly consanguineous family, formerly diagnosed as oculo-oto-facial dysplasia, the four affected individuals were homozygous for a 34 bp promoter deletion, which differed from the promoter deletion in the other families. Reporter gene and in vivo assays showed that the promoter deletions led to reduced expression of TXNL4A. Depletion of TXNL4A (Dib1) in yeast demonstrated reduced assembly of the tri-snRNP complex. Our results indicate that BMKS is an autosomal-recessive condition, which is frequently caused by compound heterozygosity of low-frequency promoter deletions in combination with very rare loss-of-function mutations. Copyright © 2014 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Nov 2014 · The American Journal of Human Genetics
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    ABSTRACT: Acromelic frontonasal dysostosis (AFND) is a rare disorder characterized by distinct craniofacial, brain, and limb malformations, including frontonasal dysplasia, interhemispheric lipoma, agenesis of the corpus callosum, tibial hemimelia, preaxial polydactyly of the feet, and intellectual disability. Exome sequencing of one trio and two unrelated probands revealed the same heterozygous variant (c.3487C>T [p. Arg1163Trp]) in a highly conserved protein domain of ZSWIM6; this variant has not been seen in the 1000 Genomes data, dbSNP, or the Exome Sequencing Project. Sanger validation of the three trios confirmed that the variant was de novo and was also present in a fourth isolated proband. In situ hybridization of early zebrafish embryos at 24 hr postfertilization (hpf) demonstrated telencephalic expression of zswim6 and onset of midbrain, hindbrain, and retinal expression at 48 hpf. Immunohistochemistry of later-stage mouse embryos demonstrated tissue-specific expression in the derivatives of all three germ layers. qRT-PCR expression analysis of osteoblast and fibroblast cell lines available from two probands was suggestive of Hedgehog pathway activation, indicating that the ZSWIM6 mutation associated with AFND may lead to the craniofacial, brain and limb malformations through the disruption of Hedgehog signaling.
    Preview · Article · Aug 2014 · The American Journal of Human Genetics
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    ABSTRACT: Craniofacial microsomia (CFM) is a complex condition associated with microtia, mandibular hypoplasia, and preauricular tags. It is the second most common congenital facial condition treated in many craniofacial centers and requires longitudinal multidisciplinary patient care. The purpose of this article is to summarize current recommendations for clinical management and discuss opportunities to advance clinical research in CFM. © 2013 Wiley Periodicals, Inc.
    No preview · Article · Nov 2013 · American Journal of Medical Genetics Part C Seminars in Medical Genetics
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    ABSTRACT: Background: Metopic craniosynostosis can occur in isolation or in conjunction with other congenital anomalies. The surgical decision making and outcomes between these 2 groups are analyzed. Methods: A retrospective review of all children evaluated in the craniofacial clinic at Seattle Children’s Hospital for metopic craniosynostosis between 2004 and 2009 was performed. Physical examination and CT scan characteristics were analyzed as were the treatment decisions and surgical outcomes. Results: From 2004 to 2009, 282 patients were evaluated and 100 were determined to have metopic craniosynostosis. Of these, 19 patients were found to have additional congenital anomalies. Review of these patients’ CT scans revealed 13 with classic trigonencephaly, 3 with microcephaly, and 3 with narrow frontal bones, abnormal orbits, and small anterior fossa. Patients (90%) with isolated metopic craniosynostosis underwent cranial vault expansion, whereas only 63% of the complex group did so. The complex metopic group had a longer hospital stay (5 d vs 3.4 d), more intraoperative complications, and required more repeat surgery. Conclusion: Patients with metopic craniosynostosis and additional anomalies require special consideration when deciding upon surgical intervention and should be cared for by a multidisciplinary team to address their additional needs.
    Full-text · Article · Oct 2013
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    ABSTRACT: Frontonasal Dysplasia (FND) and Oculo-auriculo-vertebral spectrum (OAVS) are two well-recognized clinical entities. With features of both FND and OAVS, the term oculoauriculofrontonasal syndrome (OAFNS) was coined in 1981. The OAFNS phenotype combines elements of abnormal morphogenesis of the frontonasal and maxillary process (derived from forebrain neural crest) with abnormal development of the first and second branchial arches (derived from hindbrain neural crest). We present a case series of 33 children with OAFNS ascertained from a comprehensive review of the literature and report an additional retrospective series of eight patients displaying features consistent with OAFNS. Notably, in a subset of our cases, we have observed abnormalities in nasal ossification and bony structures of the maxilla that have not previously described in OAFNS and are not seen in either FND or OAVS. We present the phenotype and novel naso-maxillary findings and explore potential etiologic and developmental pathways for OAFNS. We highlight the differences in phenotypic characteristics of OAFNS compared to OAVS and FND. These observations support the classification of OAFNS as a discrete syndrome. Further phenotypic refinements of OAFNS are needed to understand pathogenesis of this syndrome and the newly described nasal malformation may help identify the etiology. © 2013 Wiley Periodicals, Inc.
    No preview · Article · Jun 2013 · American Journal of Medical Genetics Part A
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    ABSTRACT: The metopic suture is the only calvarial suture which normally closes during infancy. Upon closure, a palpable and visible ridge often forms which can be confused with metopic craniosynostosis. Metopic ridging (MR) is treated nonsurgically while metopic craniosynostosis (MCS) is treated surgically. Differentiating between the two is paramount; however, consensus is lacking about where a clear diagnostic threshold lies. The goal of this study is to describe the physical examination and CT scan characteristics which may help to differentiate between physiological closure of the metopic suture with ridging (MR) and MCS. A retrospective chart review of all patients seen at Seattle Children's Hospital between 2004 and 2009 with the diagnosis of either MCS or MR (n = 282) was performed. Physical examination characteristics described by diagnosing practitioners were analyzed. Clinical photos were assessed by 3 expert raters to determine the importance of these characteristics. CT scan findings were abstracted and compared between the two diagnoses. The "classic" triad of narrow forehead, biparietal widening, and hypotelorism was present in only 14% of patients with MCS. Ninety-eight percent of patients in both groups had a palpable metopic ridge. The photographic finding of narrow forehead and pterional constriction was present in all patients with MCS, but only in 11.2% and 2.8% of patients with MR. On CT scan, the presence of 3 or more MCS findings was diagnostic of MCS in 96% of patients. Patients with MCS were more likely to present before 6 months of age (66% vs. 32%). Patients with MCS tend to present earlier than those with MR. Upon physical examination, the relationship between the lateral frontal bone and the lateral orbit is important in distinguishing between the two diagnoses. A CT scan can be helpful in making the diagnosis not to confirm a closed suture but to identify 3 or more MCS characteristics.
    Full-text · Article · Jan 2013 · The Journal of craniofacial surgery
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    ABSTRACT: Heterozygous mutations in the EFTUD2 were identified in 12 individuals with a rare sporadic craniofacial condition termed Mandibulofacial dysostosis with microcephaly (MIM 610536). We present clinical and radiographic features of three additional patients with de novo heterozygous mutations in EFTUD2. Although clinical features overlap with findings of the original report (choanal atresia, cleft palate, maxillary and mandibular hypoplasia, and microtia), microcephaly was present in two of three patients and cognitive impairment was milder in those with head circumference proportional to height. Our cases expand the phenotypic spectrum to include epibulbar dermoids and zygomatic arch clefting. We suggest that craniofacial computed tomography studies to assess cleft of zygomatic arch may assist in making this diagnosis. We recommend consideration of EFTUD2 testing in individuals with features of oculo-auriculo-vertebral spectrum and bilateral microtia, or individuals with atypical CHARGE syndrome who do not have a CHD7 mutation, particularly those with a zygomatic arch cleft. The absence of microcephaly in one patient indicates that it is a highly variable phenotypic feature. © 2012 Wiley Periodicals, Inc.
    No preview · Article · Jan 2013 · American Journal of Medical Genetics Part A
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    ABSTRACT: Background: Craniofacial microsomia (CFM) is a congenital condition characterized by microtia and mandibular underdevelopment. Healthcare databases and birth defects surveillance programs could be used to improve knowledge of CFM. However, no specific International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code exists for this condition, which makes standardized data collection challenging. Our aim was to evaluate the validity of existing ICD-9-CM codes to identify individuals with CFM. Methods: Study sample eligibility criteria were developed by an expert panel and matched to 11 ICD-9-CM codes. We queried hospital discharge data from two craniofacial centers and identified a total of 12,254 individuals who had ≥1 potentially CFM-related code(s). We reviewed all (n = 799) medical records identified at the University of North Carolina (UNC) and 500 randomly selected records at Seattle Children's Hospital (SCH). Individuals were classified as a CFM case or non-case. Results: Thirty-two individuals (6%) at SCH and 93 (12%) at UNC met the CFM eligibility criteria. At both centers, 59% of cases and 95% of non-cases had only one code assigned. At both centers, the most frequent codes were 744.23 (microtia), 754.0 and 756.0 (nonspecific codes), and the code 744.23 had a positive predictive value (PPV) >80% and sensitivity >70%. The code 754.0 had a sensitivity of 3% (PPV <1%) at SCH and 36% (PPV = 5%) at UNC, whereas 756.0 had a sensitivity of 38% (PPV = 5%) at SCH and 18% (PPV = 26%) at UNC. Conclusions: These findings suggest the need for a specific CFM code to facilitate CFM surveillance and research.
    Full-text · Article · Dec 2012 · Birth Defects Research Part A Clinical and Molecular Teratology
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    ABSTRACT: Auriculocondylar syndrome (ACS) is a rare, autosomal-dominant craniofacial malformation syndrome characterized by variable micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic "question-mark" ear malformation. Careful phenotypic characterization of severely affected probands in our cohort suggested the presence of a mandibular patterning defect resulting in a maxillary phenotype (i.e., homeotic transformation). We used exome sequencing of five probands and identified two novel (exclusive to the patient and/or family studied) missense mutations in PLCB4 and a shared mutation in GNAI3 in two unrelated probands. In confirmatory studies, three additional novel PLCB4 mutations were found in multigenerational ACS pedigrees. All mutations were confirmed by Sanger sequencing, were not present in more than 10,000 control chromosomes, and resulted in amino-acid substitutions located in highly conserved protein domains. Additionally, protein-structure modeling demonstrated that all ACS substitutions disrupt the catalytic sites of PLCB4 and GNAI3. We suggest that PLCB4 and GNAI3 are core signaling molecules of the endothelin-1-distal-less homeobox 5 and 6 (EDN1-DLX5/DLX6) pathway. Functional studies demonstrated a significant reduction in downstream DLX5 and DLX6 expression in ACS cases in assays using cultured osteoblasts from probands and controls. These results support the role of the previously implicated EDN1-DLX5/6 pathway in regulating mandibular specification in other species, which, when disrupted, results in a maxillary phenotype. This work defines the molecular basis of ACS as a homeotic transformation (mandible to maxilla) in humans.
    Full-text · Article · May 2012 · The American Journal of Human Genetics
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    ABSTRACT: Craniofacial anomalies comprise a frequent cause of birth defects requiring surgical treatment. A subset of children with craniofacial anomalies will have additional birth defects, developmental delays, or recognizable genetic syndromes. Genetic consultation should be offered to the families of children in this subgroup. The overall goal of a genetic consultation is the identification of a unifying diagnosis to direct medical management and provide families with information regarding prognosis and recurrence risk. Current clinical genetic testing options for children with recognizable craniofacial syndromes include single-gene-targeted mutation analysis, complete gene sequencing, and gene duplication/deletion analysis. Testing options for children who have multiple birth defects without a recognizable genetic syndrome include karyotype analysis and array comparative genomic hybridization. Future testing may include exome or whole-genome sequencing. In this article, we will discuss indications for genetic consultation and review current and future gene testing options for craniofacial conditions.
    No preview · Article · Jan 2012 · The Journal of craniofacial surgery
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    ABSTRACT: Microtia is a congenital anomaly of the ear that ranges in severity from mild structural abnormalities to complete absence of the ear, and can occur as an isolated birth defect or as part of a spectrum of anomalies or a syndrome. Microtia is often associated with hearing loss and patients typically require treatment for hearing impairment and surgical ear reconstruction. The reported prevalence varies among regions, from 0.83 to 17.4 per 10,000 births, and the prevalence is considered to be higher in Hispanics, Asians, Native Americans, and Andeans. The etiology of microtia and the cause of this wide variability in prevalence are poorly understood. Strong evidence supports the role of environmental and genetic causes for microtia. Although some studies have identified candidate genetic variants for microtia, no causal genetic mutation has been confirmed. The application of novel strategies in developmental biology and genetics has facilitated elucidation of mechanisms controlling craniofacial development. In this paper we review current knowledge of the epidemiology and genetics of microtia, including potential candidate genes supported by evidence from human syndromes and animal models. We also discuss the possible etiopathogenesis in light of the hypotheses formulated to date: Neural crest cells disturbance, vascular disruption, and altitude. © 2011 Wiley Periodicals, Inc.
    Full-text · Article · Jan 2012 · American Journal of Medical Genetics Part A
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    ABSTRACT: Abstract Bathrocephaly, a deformity of the posterior skull with bulging of the mid-portion of the occipital bone, is often associated with a benign variant of the mendosal suture (Mulliken and Le, 2008). The endochondral and membranous portions of the occipital bone converge at the mendosal suture, which normally closes during fetal life or early infancy. When it persists, it is associated with a characteristic head shape that requires no intervention. We review the clinical findings associated with postnatal persistence of the mendosal suture and discuss other factors that may be associated with bathrocephaly. Key Words: mendosal suture, craniosynostosis, occipital protuberance, bathrocephaly, cephalohematoma.
    No preview · Article · Oct 2011 · The Cleft Palate-Craniofacial Journal
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    ABSTRACT: The triad of micrognathia, glossoptosis, and resultant airway obstruction is known as Robin sequence (RS). Although RS is a well-recognized clinical entity, there is wide variability in the diagnosis and care of children born with RS. Systematic evaluations of treatments and clinical outcomes for children with RS are lacking despite the advances in clinical care over the past 20 years. We explore the pathogenesis, developmental and genetic models, morphology, and syndromes and malformations associated with RS. Current classification systems for RS do not account for the heterogeneity among infants with RS, and they do not allow for prediction of the optimal management course for an individual child. Although upper airway obstruction for some infants with RS can be treated adequately with positioning, other children may require a tracheostomy. Care must be customized for each patient with RS, and health care providers must understand the anatomy and mechanism of airway obstruction to develop an individualized treatment plan to improve breathing and achieve optimal growth and development. In this article we provide a comprehensive overview of evaluation strategies and therapeutic options for children born with RS. We also propose a conceptual treatment protocol to guide the provider who is caring for a child with RS.
    Preview · Article · Apr 2011 · PEDIATRICS
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    ABSTRACT: The genetic contribution to the pathogenesis of isolated single suture craniosynostosis is poorly understood. The role of mutations in genes known to be associated with syndromic synostosis appears to be limited. We present our findings of a candidate gene resequencing approach to identify rare variants associated with the most common forms of isolated craniosynostosis. Resequencing of the coding regions, splice junction sites, and 5' and 3' untranslated regions of 27 candidate genes in 186 cases of isolated non-syndromic single suture synostosis revealed three novel and two rare sequence variants (R406H, R595H, N857S, P190S, M446V) in insulin-like growth factor I receptor (IGF1R) that are enriched relative to control samples. Mapping the resultant amino acid changes to the modeled homodimer protein structure suggests a structural basis for segregation between these and other disease-associated mutations found in IGF1R. These data suggest that IGF1R mutations may contribute to the risk and in some cases cause single suture craniosynostosis.
    Full-text · Article · Jan 2011 · American Journal of Medical Genetics Part A
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    ABSTRACT: The short arm of chromosome 16 is rich in segmental duplications, predisposing this region of the genome to a number of recurrent rearrangements. Genomic imbalances of an approximately 600-kb region in 16p11.2 (29.5-30.1 Mb) have been associated with autism, intellectual disability, congenital anomalies, and schizophrenia. However, a separate, distal 200-kb region in 16p11.2 (28.7-28.9 Mb) that includes the SH2B1 gene has been recently associated with isolated obesity. The purpose of this study was to better define the phenotype of this recurrent SH2B1-containing microdeletion in a cohort of phenotypically abnormal patients not selected for obesity. Array comparative hybridization was performed on a total of 23,084 patients in a clinical setting for a variety of indications, most commonly developmental delay. Deletions of the SH2B1-containing region were identified in 31 patients. The deletion is enriched in the patient population when compared with controls (P = 0.003), with both inherited and de novo events. Detailed clinical information was available for six patients, who all had developmental delays of varying severity. Body mass index was ≥95th percentile in four of six patients, supporting the previously described association with obesity. The reciprocal duplication, found in 17 patients, does not seem to be significantly enriched in our patient population compared with controls. Deletions of the 16p11.2 SH2B1-containing region are pathogenic and are associated with developmental delay in addition to obesity.
    Preview · Article · Oct 2010 · Genetics in medicine: official journal of the American College of Medical Genetics
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    ABSTRACT: Little is known about genes that underlie isolated single-suture craniosynostosis. In this study, we hypothesize that rare copy number variants (CNV) in patients with isolated single-suture craniosynostosis contain genes important for cranial development. Using whole genome array comparative genomic hybridization (CGH), we evaluated DNA from 186 individuals with single-suture craniosynostosis for submicroscopic deletions and duplications. We identified a 1.1 Mb duplication encompassing RUNX2 in two affected cousins with metopic synostosis and hypodontia. Given that RUNX2 is required as a master switch for osteoblast differentiation and interacts with TWIST1, mutations in which also cause craniosynostosis, we conclude that the duplication in this family is pathogenic, albeit with reduced penetrance. In addition, we find that a total of 7.5% of individuals with single-suture synostosis in our series have at least one rare deletion or duplication that contains genes and that has not been previously reported in unaffected individuals. The genes within and disrupted by CNVs in this cohort are potential novel candidate genes for craniosynostosis.
    Full-text · Article · Sep 2010 · American Journal of Medical Genetics Part A
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    ABSTRACT: Quantification of facial characteristics is important for research in dysmorphology, otolaryngology, oral and maxillofacial, and plastic surgical disciplines, among others. Three-dimensional surface imaging systems offer a quick and practical method for quantifying craniofacial variation and appear to be highly reliable. However, some sources of measurement error have not yet been thoroughly evaluated. The authors assessed the reliability of using stereophotogrammetry for measuring craniofacial characteristics in 40 individuals, including 20 without craniofacial conditions and 20 with 22q11.2 deletion syndrome. The authors recruited staff and relatives of staff, and individuals with a laboratory-confirmed 22q11.2 deletion. Thirty anthropometric measurements were obtained on participants and on three-dimensional images. Intrarater and interrater reliability for most interlandmark distances on three-dimensional images had intraclass correlation coefficients greater than 95 percent, mean absolute differences of less than 1 mm, relative error measurement less than 5, and technical error of measurement less than 1 mm. The Pearson correlation coefficients of greater than 0.9 for most distances suggest high intermethod reliability between direct and image-based measurements. Three-dimensional image-based measurements were systematically larger for the head length and width, forehead, and skull base widths, and upper and lower facial widths. This study provides further evidence of the high reliability of three-dimensional imaging systems for several craniofacial measurements, including landmarks and interlandmark distances not included in previous studies. The authors also discuss possible errors introduced with palpable landmarks and when working with less compliant participants, such as children. The authors offer guidelines for establishing protocols that can be tailored to each population and research question to maximize the accuracy of image-based measurements.
    Full-text · Article · Oct 2009 · Plastic and Reconstructive Surgery
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    ABSTRACT: Multisutural craniosynostosis that includes bilateral lambdoid and sagittal synostosis (BLSS) results in a very characteristic head shape with frontal bossing, turribrachycephaly, biparietal narrowing, occipital concavity, and inferior displacement of the ears. This entity has been reported both in the genetics literature as craniofacial dyssynostosis and in the surgical literature as "Mercedes Benz" syndrome. Craniofacial dyssynostosis was first described in 1976 by Dr. Neuhauser when he presented a series of seven patients with synostosis of the sagittal and lambdoid sutures, short stature, and developmental delay. Over the past 30 years nine additional patients with craniofacial dyssynostosis have been reported in the literature adding to the growing evidence for a distinct craniosynostosis syndrome. The term "Mercedes Benz" syndrome was coined by Moore et al. in 1998 due to the characteristic appearance of the fused sutures on three-dimensional CT imaging. In contrast to the aforementioned reported cases of craniofacial dyssynostosis, all three patients had normal development. Recently, there have been several case reports of patients with BLSS and distinct chromosomal anomalies. These findings suggest that BLSS is a heterogeneous disorder perhaps with syndromic, chromosomal, and isolated forms. In this manuscript we will present the largest series of patients with BLSS and review clinical, CT, and molecular findings.
    No preview · Article · May 2009 · American Journal of Medical Genetics Part A
  • Carrie L Heike · Anne V Hing
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    ABSTRACT: Craniofacial microsomia (CFM) includes a spectrum of malformations primarily involving structures derived from the first and second branchial arches. Findings include facial asymmetry resulting from maxillary and/or mandibular hypoplasia; preauricular or facial tags; ear malformations that can include microtia (hypoplasia of the external ear), anotia (absence of the external ear), or aural atresia (absence of the external ear canal); and hearing loss. Severity can range from subtle facial asymmetry with a small skin tag in front of an otherwise normal-appearing ear to bilateral involvement (typically asymmetric), microtia/anotia with atresia of the ear canals, microphthalmia, and respiratory compromise from severe mandibular hypoplasia. Other craniofacial malformations including cleft lip and/or palate can be seen. Non-craniofacial malformations, especially vertebral, cardiac, and limb, can be seen. The diagnosis of CFM is based on clinical findings. CFM most frequently occurs as a simplex case (i.e., occurrence in a single individual in a family) with unknown etiology; recurrence risks are empiric. If an individual with CFM is found to have an inherited or de novo chromosome abnormality, genetic counseling for that condition is indicated. Occasional autosomal dominant or autosomal recessive inheritance is observed. If a proband has CFM and no reported family history of CFM, the risk to sibs is two to three percent; this may be an underestimate because of the difficulty of obtaining an accurate family history for some of the subtle features of CFM. Treatment of manifestations: For optimal outcome children with CFM require timely and coordinated assessments and interventions. Ideally, children should be managed by an experienced multidisciplinary craniofacial team. The goals of treatment for CFM are to assure adequate respiratory support and feeding in infants with severe facial malformations, maximize hearing and communication, improve facial symmetry, and optimize dental occlusion. Treatment is age-dependent, with time-sensitive interventions at appropriate stages of craniofacial growth and development.
    No preview · Chapter · Jan 2009

Publication Stats

2k Citations
189.50 Total Impact Points

Institutions

  • 2005-2014
    • Seattle Children's Hospital
      • • Craniofacial Center
      • • Children's Hospital and Regional Medical Center
      Seattle, Washington, United States
    • Washington Regional Medical Center
      Fayetteville, Arkansas, United States
  • 2001-2014
    • University of Washington Seattle
      • • Department of Pediatrics
      • • Department of Radiology
      Seattle, Washington, United States
  • 1992-1999
    • Washington University in St. Louis
      • • Department of Pediatrics
      • • Department of Genetics
      San Luis, Missouri, United States
  • 1996
    • SickKids
      Toronto, Ontario, Canada
  • 1993
    • University of Missouri - St. Louis
      Saint Louis, Michigan, United States