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Lateral Meningocele Syndrome

Synonym: Lehman Syndrome

, MD, FRCPC, , MD, MSc, and , MD.

Author Information

Initial Posting: .

Estimated reading time: 15 minutes

Summary

Clinical characteristics.

Lateral meningocele syndrome (LMS) is characterized by multiple lateral spinal meningoceles (protrusions of the arachnoid and dura through spinal foramina), distinctive facial features, joint hyperextensibility, hypotonia, and skeletal, cardiac, and urogenital anomalies. Neurologic sequelae of the meningoceles depend on size and location and can include neurogenic bladder, paresthesias, back pain, and/or paraparesis. Other neurologic findings can include Chiari I malformation, syringomyelia, and rarely, hydrocephalus. Additional findings of LMS include mixed or conductive hearing loss and cleft palate. Skeletal abnormalities may include scoliosis, vertebral fusion, scalloping of vertebrae, and wormian bones. Although developmental delay is common, cognition is often preserved. Feeding difficulties and gastroesophageal reflux disease (GERD) are common.

Diagnosis/testing.

The diagnosis of LMS syndrome is established in a proband with consistent clinical findings and a heterozygous pathogenic variant in NOTCH3.

Management.

Treatment of manifestations: Routine management of neurologic sequelae of lateral meningoceles (neurogenic bladder, paresthesias, back pain, and/or paraparesis). Although rarely required, surgical intervention may be necessary for neurologic manifestations secondary to meningocele size and location. As needed: management by specialists in chronic pain management or rehabilitation medicine; physiotherapy to reduce the risk for joint subluxation and dislocation. Routine management of: cleft palate, hearing loss, congenital cardiac defects, GU abnormalities, feeding difficulties.

Surveillance: Ongoing monitoring by the appropriate subspecialists for neurologic, developmental, musculoskeletal, cardiovascular, genitourinary, and/or gastrointestinal issues.

Genetic counseling.

LMS is inherited in an autosomal dominant manner. Although most probands have the disorder as a result of a de novo NOTCH3 pathogenic variant, affected parent-child pairs have been reported. Each child of an individual with LMS has a 50% chance of inheriting the NOTCH3 pathogenic variant. When the NOTCH3 pathogenic variant has been identified in an affected family member, prenatal testing and preimplantation genetic testing for a pregnancy at increased risk are possible options.

Diagnosis

Formal diagnostic clinical criteria for lateral meningocele syndrome (LMS) have not been established.

Suggestive Findings

LMS should be suspected in individuals with the following findings:

  • Multiple lateral spinal meningoceles (protrusion of the arachnoid and dura through the spinal foramina). Present in all affected individuals (Figure 1). Associated neurologic findings can include: Chiari I malformation, hydrocephalus, syringomyelia, and neurogenic bladder.
  • Characteristic craniofacial appearance [Castori et al 2014, Gripp et al 2015, Ejaz et al 2016] including widely spaced eyes, highly arched eyebrows, downslanted palpebral fissures, ptosis, malar flattening, long philtrum, thin vermilion of the upper lip, high and narrow palate (cleft palate present in some individuals), micrognathia, and coarse hair with a low posterior hairline (Figure 2)
  • High nasal voice
  • Mixed or conductive hearing loss (present in some individuals)
  • Developmental delay or (rarely) intellectual disability
  • Musculoskeletal. Hypotonia, decreased muscle bulk, joint hyperextensibility with possibility of frequent dislocations, hernias, scoliosis, vertebral fusion, and scalloping of vertebrae
  • Congenital cardiovascular malformations. Aortic abnormalities (bicuspid aortic valve, aortic dilation, and coarctation of the aortic arch) and ventricular septal defects
  • Genitourinary. Cryptorchidism and hydronephrosis
  • Gastrointestinal. Poor feeding, dysphagia, and gastroesophageal reflux disease (GERD)
Figure 1. . Numerous lateral meningoceles (see arrows) protrude through the thoracic foramina in a sagittal view (a) and through the lumbar foramina in a sagittal (b) and axial (c) view.

Figure 1.

Numerous lateral meningoceles (see arrows) protrude through the thoracic foramina in a sagittal view (a) and through the lumbar foramina in a sagittal (b) and axial (c) view. The curved arrow in (a) shows a meningocele protruding from the middle cranial (more...)

Figure 2.

Figure 2.

Photographs of individuals with lateral meningocele syndrome A-D. Patient 1 at age 24 years:

Establishing the Diagnosis

The diagnosis of LMS syndrome is established in a proband with consistent clinical findings and identification of a heterozygous pathogenic variant in NOTCH3 by molecular genetic testing (see Table 1).

Molecular genetic testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing:

  • Single-gene testing. Sequence analysis of NOTCH3 is performed first, followed by gene-targeted deletion/duplication analysis if no pathogenic variant is found. Note: To date all causative pathogenic variants have been in exon 33, the last exon of NOTCH3 [Gripp et al 2015, Ejaz et al 2016]; see Molecular Genetics, Pathogenic variants.
  • A multigene panel that includes NOTCH3 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
    For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
  • More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered if single-gene testing (and/or use of a multigene panel that includes NOTCH3) fails to confirm a diagnosis in an individual with features of LMS. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation). Note: Clinicians should ensure that exome sequencing or genome sequencing has sufficient coverage to detect small deletions in the last exon of NOTCH3 as these pathogenic variants could otherwise be missed [Ejaz et al 2016].
    For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.

Table 1.

Molecular Genetic Testing Used in Lateral Meningocele Syndrome

Gene 1MethodProportion of Probands with a Pathogenic Variant 2 Detectable by Method
NOTCH3Sequence analysis 37/8 4
Gene-targeted deletion/duplication analysis 5Unknown 6
UnknownSee footnote 7
1.
2.

See Molecular Genetics for information on allelic variants detected in this gene.

3.

Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.

4.
5.

Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.

6.

No data on detection rate of gene-targeted deletion/duplication analysis are available.

7.

The one individual reported by Castori et al [2014] did not have an identifiable NOTCH3 pathogenic variant [Kym Boycott, MD; email communication February 17, 2016].

Clinical Characteristics

Clinical Description

Lateral meningocele syndrome (LMS) is characterized by multiple lateral spinal meningoceles, distinctive facial features, joint hyperextensibility, hypotonia, and skeletal, cardiac, and urogenital anomalies.

LMS is a recognizable clinical phenotype, with half of known affected individuals having a molecularly confirmed diagnosis [Gripp et al 2015]; to date, most others have not been tested for a NOTCH3 pathogenic variant.

Multiple lateral spinal meningoceles (protrusions of the arachnoid and dura through the spinal foramina) are found in all affected individuals. Neurologic sequelae of the meningoceles can include neurogenic bladder, paresthesias, back pain, and/or paraparesis depending on size and location. Other neurologic findings can include Chiari I malformation (4/14), syringomyelia (3/14) and rarely, hydrocephalus [Gripp et al 1997, Castori et al 2014, Gripp et al 2015, Ejaz et al 2016].

Head and neck. Mixed or conductive hearing loss has been noted in seven of 14 individuals with LMS. Cleft palate is occasionally seen. Eye abnormalities can include iris coloboma, proptosis, and oculomotor restriction [Castori et al 2014, Gripp et al 2015, Ejaz et al 2016].

Developmental delay is frequently seen in individuals with LMS but cognition is often preserved. All seven individuals with a molecularly confirmed diagnosis had developmental delay, and one also had intellectual disability [Gripp et al 2015, Ejaz et al 2016]. Psychomotor development may vary within a family; for example, in an affected mother-daughter pair only the daughter had developmental delay [Lehman et al 1977].

Musculoskeletal. Overlap with features of connective tissue disorders include neonatal hypotonia (11/14), abdominal hernias (9/14), ligamentous laxity (12/14), keloid scars (5/14), and back pain (3/14) in later life.

Nonspecific muscle or generalized pain has been described. One woman age 55 years had multiple joint dislocations [Castori et al 2014].

Many individuals have skeletal changes including scoliosis, vertebral fusion, scalloping of vertebrae, and wormian bones [Gripp et al 1997, Castori et al 2014, Gripp et al 2015].

Congenital cardiovascular malformations described in five individuals with a molecularly confirmed diagnosis include ventricular septal defect (3), bicuspid aortic valve (2), dilatation of the aorta (2), and coarctation of the aortic arch (1) [Alves et al 2013, Gripp et al 2015, Ejaz et al 2016].

Genitourinary. Cryptorchidism is frequently seen. Hydronephrosis has been occasionally reported [Castori et al 2014].

Gastrointestinal. Infants with LMS may demonstrate dysphagia with poor weight gain. Dysphagia was severe enough to warrant gastrostomy tube feeding in one [Ejaz et al 2016].

Gastroesophageal reflux disease (GERD) which can persist into adulthood has been described in a woman age 55 years, the oldest reported individual with LMS to date [Castori et al 2014]. Of note, she did not have a NOTCH3 pathogenic variant on exome sequencing and targeted sequencing [Kym Boycott, MD; email communication 2-17-16].

Genotype-Phenotype Correlations

Given that lateral meningocele syndrome (LMS) is a rare disorder with fewer than 20 reported cases, no genotype-phenotype correlations have been determined.

Penetrance

Penetrance appears to be complete but data are limited.

Nomenclature

Lehman et al [1977] first described a woman with dysmorphic facial features, skeletal sclerosis, and multiple meningoceles, and her mother with similar craniofacial dysmorphisms. Philip et al [1995], who published a second case, named the syndrome after Lehman. The authors prefer the term "lateral meningocele syndrome" as it emphasizes the hallmark feature of the condition.

Prevalence

Lateral meningocele syndrome is very rare, with approximately 14 reported individuals, seven of whom have a molecularly confirmed diagnosis. There does not appear to be increased prevalence in specific populations.

Differential Diagnosis

The differential diagnosis for lateral meningocele syndrome (LMS) can include the following:

  • Hadju-Cheney syndrome (OMIM 102500), a skeletal disorder caused by a heterozygous pathogenic variant in NOTCH2, is characterized by dysmorphic facial features (e.g., malar flattening, thick eyebrows, micrognathia), osteoporosis with acro-osteolysis, wormian bones, premature loss of dentition, and joint laxity. One individual with LMS was initially misdiagnosed with Hadju-Cheney syndrome due to the presence of acro-osteolysis [Avela et al 2011, Gripp 2011].
  • Marfan syndrome. LMS has significant overlap with other connective tissue disorders. Spinal meningeal anomalies, specifically dural ectasias, are frequently seen in Marfan syndrome. Individuals with Marfan syndrome may also have joint laxity, scoliosis, cardiovascular anomalies, and some shared facial features, such as malar flattening and retrognathia. Marfan syndrome is inherited in an autosomal dominant manner and is caused by mutation of FBN1.
  • Noonan syndrome. LMS and Noonan syndrome share similarities in their characteristic facial features (including widely spaced eyes, ptosis, epicanthus, and low-set ears with increased posterior angulation) and a low posterior hairline. Prenatal signs of Noonan syndrome, such as a nuchal edema and congenital cardiac defect, were also seen in one individual with LMS [Ejaz et al 2016]. Noonan syndrome is inherited in an autosomal dominant manner. Genes known to be associated with the disorder include PTPN11, SOS1, RAF1, RIT1, and KRAS.
  • Neurofibromatosis type 1. Lateral meningoceles and dural ectasia have been described in some individuals with NF1 [Ueda et al 2015]. The distincitve facial features of LMS are not seen in individuals with NF1; other distinctive characteristics of NF1 include café-au-lait spots, neurofibromas, and Lisch nodules. NF1 and LMS may also have similar skeletal and neurologic changes including scoliosis, hydrocephalus, and developmental delays. NF1 is inherited in an autosomal dominant manner and is caused by mutation of NF1.

Management

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with lateral meningocele syndrome (LMS), the following evaluations are recommended:

  • Spine MRI to assess for meningoceles (if not performed at time of diagnosis) and neurosurgical assessment to evaluate the effect of lateral spinal meningocele size and location on neurologic function
  • Brain MRI to assess for Chiari I malformation or hydrocephalus, if not performed at time of diagnosis
  • Thorough physical and neurologic examination for signs of neuropathy, joint abnormalities, and abdominal hernias
  • Neurocognitive assessment
  • Assessment by general surgery for abdominal hernia repair
  • Assessment by orthopedic surgery for symptomatic skeletal deformities
  • Visualization of the aortic arch by echocardiogram or MRI
  • Urologic assessment for cryptorchidism if present
  • Feeding assessment
  • Hearing assessment
  • Ophthalmologic assessment
  • Consultation with a clinical geneticist and/or genetic counselor

Treatment of Manifestations

Specific treatment for LMS does not currently exist. Supportive management of the clinical finding depends on the involved system as outlined below.

Lateral spinal meningoceles. Symptomatic treatment of neurologic sequelae (e.g., neurogenic bladder, paresthesias, back pain, and/or paraparesis) is as per routine.

Although rarely required, surgical intervention may be necessary for neurologic manifestations secondary to meningocele size and location. When required, surgical approach is individualized and can include laminectomy for smaller meningoceles and costotransversectomy for larger meningoceles [Kim et al 2011]. Of note, the 55-year-old woman with LMS experienced irreversible nerve damage following surgery for two lumbosacral meningoceles (to manage back and referred neuropathic pain) [Castori et al 2014].

Psychomotor development. Provide timely supportive interventions as needed to optimize development through occupational therapy and education resources.

Musculoskeletal

  • Management by specialists in chronic pain management or rehabilitation medicine as needed
  • Physiotherapy to reduce risk for joint subluxation and dislocation

Routine management of the following:

  • Cleft palate
  • Hearing loss
  • Congenital cardiac defects
  • Genitourinary abnormalities
  • GERD. Note that a feeding tube may be necessary if persistent feeding difficulties result in failure to thrive.

Surveillance

No surveillance guidelines for LMS have been published.

Ongoing monitoring by the appropriate subspecialists for neurologic, developmental, musculoskeletal, cardiovascular, genitourinary, and/or gastrointestinal issues is indicated.

Evaluation of Relatives at Risk

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Lateral meningocele syndrome (LMS) is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

Sibs of a proband

  • The risk to the sibs of the proband depends on the genetic status of the proband’s parents.
  • If a parent of the proband is affected, the risk to the sibs is 50%.
  • When the parents are clinically unaffected, the risk to the sibs of a proband appears to be low.
  • If the NOTCH3 pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the risk to sibs is slightly greater than that of the general population (though still <1%) because of the theoretic possibility of parental germline mosaicism.

Offspring of a proband. Each child of an individual with LMS has a 50% chance of inheriting the NOTCH3 pathogenic variant.

Other family members. The risk to other family members depends on the status of the proband's parents: if a parent is affected, his or her family members may be at risk.

Related Genetic Counseling Issues

Considerations in families with an apparent de novo pathogenic variant. When neither parent of a proband with LMS has the pathogenic variant or clinical evidence of the disorder, the NOTCH3 pathogenic variant is likely de novo. However, non-medical explanations including alternate paternity or maternity (e.g., with assisted reproduction) or undisclosed adoption could also be explored.

Family planning

  • The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy.
  • It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to the parents of affected individuals and young adults who are affected.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Testing

Once the NOTCH3 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic testing for LMS are possible.

Resources

GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.

No specific resources for Lateral Meningocele Syndrome have been identified by GeneReviews staff.

Molecular Genetics

Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED.

Table A.

Lateral Meningocele Syndrome: Genes and Databases

Data are compiled from the following standard references: gene from HGNC; chromosome locus from OMIM; protein from UniProt. For a description of databases (Locus Specific, HGMD, ClinVar) to which links are provided, click here.

Table B.

OMIM Entries for Lateral Meningocele Syndrome (View All in OMIM)

130720LATERAL MENINGOCELE SYNDROME; LMNS
600276NOTCH RECEPTOR 3; NOTCH3

Molecular Pathogenesis

Lateral meningocele syndrome (LMS) is caused by heterozygous, likely gain-of-function, pathogenic variants in NOTCH3. NOTCH3 is a part of a highly conserved signaling pathway that is responsible for cell differentiation, proliferation, and apoptosis, through regulating transcription of target genes.

Gene structure. NOTCH3 comprises 33 exons and has a transcript length of approximately 8.089 kb (NM_000435.2). For a detailed summary of gene and protein information, see Table A, Gene.

Pathogenic variants. To date, all seven pathogenic variants reported in LMS occurred in exon 33, the last exon of NOTCH3. These include three missense variants, two deletions, and one insertion [Gripp et al 2015, Ejaz et al 2016]. See Table 2.

Table 2.

NOTCH3 Pathogenic Variants Discussed in This GeneReview

DNA Nucleotide Change
(Alias 1)
Predicted Protein Change
(Alias 1)
Reference Sequences
c.6247A>Tp.Lys2083TerNM_000435​.2
NP_000426​.2
c.6461_6486delp.Gly2154fsTer78
c.6498_6577delp.Ala2167ProfsTer48
c.6692dupC
(6692_6693delC)
p.Ala2233GlyfsTer9
(Pro2231fsTer11)
c.6663C>Gp.Tyr2221Ter
c.6732C>Ap.Tyr2244Ter

Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.

GeneReviews follows the standard naming conventions of the Human Genome Variation Society (varnomen​.hgvs.org). See Quick Reference for an explanation of nomenclature.

1.

Variant designation that does not conform to current naming conventions

Normal gene product. NOTCH3 encodes the neurogenic locus notch homolog protein 3 (NOTCH3), a transmembrane receptor involved in cell signaling and activation of target genes. It appears to be universally expressed. NOTCH3 comprises of 2321 amino acids with extracellular, transmembrane, and intracellular components. The 34 EGF-like domains and three Lin/Notch repeats lie within the extracellular region; the five ANK repeats, one membrane-proximal RAM domain, and one C-terminal PEST domain lie intracellularly. Activation of the extracellular domain via ligand binding results in intracellular release of NOTCH3 intracellular domain (NICD), which enters the nucleus and interacts with specific transcription factors to regulate target gene transcription [Bellavia et al 2008].

Abnormal gene product. The NOTCH3 nonsense or frameshift pathogenic variants occur in exon 33, the last exon. It is predicted that the transcripts of such variants in this location escape nonsense-mediated decay and express a truncated NOTCH3 protein, which has been documented in the cells of one patient [Gripp et al 2015]. Through negative regulation of protein stability these truncated NOTCH3 proteins would lack the C-terminal PEST domain which is responsible for degradation of the intracellular signaling portion of activated NOTCH3. The truncated protein is more likely to escape degradation, thereby prolonging its cellular half-life [Bellavia et al 2008, Wang et al 2015]. Therefore, the LMS phenotype is thought to be caused by NOTCH3 gain-of-function variants [Gripp et al 2015, Wang et al 2015]. The precise mechanism by which excess NOTCH3 results in LMS is not understood. The protein has been shown to promote proliferation of vascular smooth muscle; this aberrant protein function may contribute to the aortic anomalies seen in a few individuals with LMS [Baeten & Lilly 2015].

References

Literature Cited

  • Alves D, Sampaio M, Figueiredo R, Leao M. Lateral meningocele syndrome: additional report and further evidence supporting a connective tissue basis. Am J Med Genet A. 2013;161A:1768–72. [PubMed: 23696373]
  • Avela K, Valanne L, Helenius I, Mäkitie O. Hajdu-Cheney syndrome with severe dural ectasia. Am J Med Genet A. 2011;155A:595–8. [PubMed: 21337686]
  • Baeten JT, Lilly B. Differential regulation of NOTCH2 and NOTCH3 contribute to their unique functions in vascular smooth muscle cells. J Biol Chem. 2015;290:16226–37. [PMC free article: PMC4481222] [PubMed: 25957400]
  • Bellavia D, Checquolo S, Campese AF, Felli MP, Gulino A, Screpanti I. Notch3: from subtle differences to functional diversity. Oncogene. 2008;27:5092–98. [PubMed: 18758477]
  • Castori M, Morlino S, Ritelli M, Brancati F, De Bernardo C, Colombi M, Grammatico P. Late diagnosis of lateral meningocele syndrome in a 55-year-old woman with symptoms of joint instability and chronic musculoskeletal pain. Am J Med Genet A. 2014;164A:528–34. [PubMed: 24311540]
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  • Chida A, Shintani M, Matsushita Y, Sato H, Eitoku T, Nakayama T, Furutani Y, Hayama E, Kayamura Y, Inai K. Ohtsuki, Saji, Nonoyama S, Nakanishi T. Mutations of NOTCH3 in childhood pulmonary hypertension. Mol Genet Genomic Med. 2014;2:229–39. [PMC free article: PMC4049363] [PubMed: 24936512]
  • Ejaz R, Qin W, Huang L, Blaser S, Tetreault M, Hartley T, Boycott KM, Carter MT, et al. Lateral meningocele (Lehman) syndrome: A child with a novel NOTCH3 mutation. Am J Med Genet A. 2016;170A:1070–5. [PubMed: 26754023]
  • Gripp KW. Lateral meningocele syndrome and Hajdu-Cheney syndrome: different disorders with overlapping phenotypes. Am J Med Genet. 2011;155A:1773–4. [PubMed: 21671395]
  • Gripp KW, Robbins KM, Sobreira NL, Witmer PD, Bird LM, Avela K, Makitie O, Alves D, Hogue JS, Zackai EH, Doheny KF, Stabley DL, Sol-Church K. Truncating mutations in the last exon of NOTCH3 cause lateral meningocele syndrome. Am J Med Genet Part A. 2015;167A:271–81. [PMC free article: PMC5589071] [PubMed: 25394726]
  • Gripp KW, Scott CI Jr, Hughes HE, Wallerstein R, Nicholson L, States L, Bason LD, Kaplan P, Zderic SA, Duhaime AC, Miller F, Magnusson MR, Zackai EH. Lateral meningocele syndrome: three new patients and review of the literature. Am J Med Genet. 1997;70:229–39. [PubMed: 9188658]
  • Kim YJ, Cho H, Yoon C, Lee C, Lee T, Seok J. Surgical treatment of thoracic meningocele associated with neurofibromatosis and kyphoscholiosis. Korean J Thorac Cardiovasc Surg. 2011;44:383–6. [PMC free article: PMC3249347] [PubMed: 22263195]
  • Lehman RA, Stears JC, Wesenberg RL, Nusbaum ED. Familial osteosclerosis with abnormalities of the nervous system and meninges. J Pediatr. 1977;90:49–54. [PubMed: 830893]
  • Martignetti JA, Tian L, Li D, Ramirez MC, Camacho-Vanegas O, Camacho SC, Guo Y, Zand DJ, Bernstein AM, Masur SK, Kim CE, Otieno FG, Hou C, Abdel-Magid N, Tweddale B, Metry D, Fournet JC, Papp E, McPherson EW, Zabel C, Vaksmann G, Morisot C, Keating B, Sleiman PM, Cleveland JA, Everman DB, Zackai E, Hakonarson H. Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis. Am J Hum Genet. 2013;92:1001–7. [PMC free article: PMC3675260] [PubMed: 23731542]
  • Philip N, Andrac L, Moncla A, Sigaudy S, Zanon N, Lena G, Choux M. Multiple lateral meningoceles, distinctive facies and skeletal anomalies: a new case of Lehman syndrome. Clin Dysmorphol. 1995;4:347–51. [PubMed: 8574426]
  • Tikka S, Baumann M, Siitonen M, Pasanen P, Pöyhönen M, Myllykangas L, Viitanen M, Fukutake T, Cognat E, Joutel A, Kalimo H. CADASIL and CARASIL. Brain Pathol. 2014;24:525–44. [PubMed: 25323668]
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Chapter Notes

Revision History

  • 23 June 2016 (bp) Review posted live
  • 19 February 2016 (re) Original submission
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