Clinical Diagnosis

The diagnosis of oral-facial-digital syndrome type I (OFD1) is established at birth in some infants on the basis of characteristic oral, facial, and digital anomalies; in other instances, the diagnosis is suspected only after polycystic kidney disease is identified in later childhood or adulthood [Coll et al 1997].

Oral. Oral findings affect primarily the tongue, palate, and teeth:

• The tongue is lobed and often described as bifid or trifid. Tongue nodules, which are usually hamartomas or lipomas, also occur in at least one third of individuals with OFD1. Ankyloglossia attributable to a short lingual frenulum is common.

• Cleft hard or soft palate, submucous cleft palate, or highly arched palate occurs in more than 50% of affected individuals. Trifurcation of the soft palate has been reported [al-Qattan 1998].

• Alveolar clefts and accessory gingival frenulae are common. These fibrous bands are hyperplastic frenulae extending from the buccal mucous membrane to the alveolar ridge, resulting in notching of the alveolar ridges.

• Dental abnormalities include missing teeth (most common), extra teeth, enamel dysplasia, and malocclusion.

Facial

• Ocular hypertelorism or telecanthus occurs in at least 33% of affected individuals.

• Hypoplasia of the alae nasi, median cleft lip, or pseudocleft upper lip is common.

• Micrognathia and downslanting palpebral fissures are common.

Digital

• Brachydactyly, syndactyly of varying degrees, and clinodactyly of the fifth finger are common.

• The other fingers, particularly the third (i.e., middle finger) may show variable radial or ulnar deviation.

• Duplicated hallux (great toe) occurs in fewer than 50% of affected individuals, and if present is usually unilateral.

• Preaxial or postaxial polydactyly of the hands occurs in 1%-2% of affected individuals.

• Radiographs of the hands often demonstrate fine reticular radiolucencies, described as irregular mineralization of the bone, with or without spicule formation of the phalanges [al-Qattan & Hassanain 1997].

Brain. Structural brain abnormalities may occur in as many as 65% of individuals with OFD1 [Thauvin-Robinet et al 2006, Saal et al 2009]. Anomalies most commonly include intracerebral cysts, agenesis of the corpus callosum, and cerebellar agenesis with or without Dandy-Walker malformation. Other reported anomalies include type 2 porencephaly (schizencephalic porencephaly), pachygyria and heterotopias, hydrocephalus, cerebral or cerebellar atrophy, and berry aneurysms, each of which has been described in a few affected individuals.

Intellect. It is estimated that as many as 50% of individuals with OFD1 have some degree of intellectual disability or learning disability. Intellectual disability depends in part on the presence of brain abnormalities, but no consistent correlation exists. When present, intellectual disability is usually mild. Severe intellectual disability in the absence of brain malformations appears to be rare.

Kidney. Renal cysts can develop from both tubules and glomeruli. Polycystic kidney disease occurs in at least 50% of individuals with OFD1 although the exact frequency is unknown. Recent data indicate that renal cystic disease is present in 60% of affected individuals older than age 18 years [Prattichizzo et al 2008]. The age of onset is most often in adulthood, but renal cysts in children as young as age two years have been described.

Molecular Genetic Testing

Gene. OFD1 is the only gene currently known to be associated with oral-facial-digital syndrome type I [Ferrante et al 2001].

Clinical testing

• Sequence analysis. A variety of mutations have been identified, the majority of which predict premature protein truncation. The reported mutation detection rate is about 80% [Nowaczyk et al 2003, Thauvin-Robinet et al 2006, Prattichizzo et al 2008].
  
  Note: Sequence analysis of genomic DNA cannot detect deletion of an exon(s) or a whole gene on the X chromosome of affected females.

• Deletion/duplication analysis. One study found that six of 131 individuals with OFDI had a deletion ranging in size from one to 14 exons. None had the same deletion. Within this group, 23% of those who did not have a mutation identified on gene sequencing were found on qPCR to have an exonic or multiexonic deletion [Thauvin-Robinet et al 2009].

Table 1. Summary of Molecular Genetic Testing Used in Oral-Facial-Digital Syndrome Type I

View in own window

Gene Symbol	Test Method	Mutations Detected	Mutation Detection Frequency by Test Method 1		Test Availability
			Affected Males	Affected Females
OFD1	Sequence analysis	Sequence variants 2	Not applicable (lethal in males)	80%	Clinical
		Partial- and whole-gene deletions		0% 3
	Duplication / deletion analysis 4	Partial- and whole-gene deletions		5%

Test Availability refers to availability in the GeneTests Laboratory Directory. GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information.

1. The ability of the test method used to detect a mutation that is present in the indicated gene

2. Examples of mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations.

3. Sequence analysis cannot detect exonic or whole-gene deletions on the X chromosome in females.

4. Testing that identifies deletions/duplications not readily detectable by sequence analysis of genomic DNA; a variety of methods including quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), or targeted array GH (gene/segment-specific) may be used. A full array GH analysis that detects deletions/duplications across the genome may also include this gene/segment. See array GH.

Interpretation of test results. For issues to consider in interpretation of sequence analysis results, click here.

Testing Strategy

To confirm/establish the diagnosis in a proband. Gene sequencing followed by qPCR for detection of deletions identifies a mutation in approximately 85% of affected individuals.

Carrier testing for at-risk relatives requires prior identification of the disease-causing mutation in the family.

Note: (1) Carriers are heterozygotes for this X-linked disorder and will likely have clinical findings related to the disorder. (2) Identification of female carriers requires either prior identification of the disease-causing mutation in the family or molecular genetic testing first by sequence analysis, and then, if no mutation is identified, by methods to detect structural abnormalities.

Prenatal diagnosis and preimplantation genetic diagnosis (PGD) for at-risk pregnancies require prior identification of the disease-causing mutation in the family.

Note: It is the policy of GeneReviews to include clinical uses of testing available from laboratories listed in the GeneTests Laboratory Directory; inclusion does not necessarily reflect the endorsement of such uses by the author(s), editor(s), or reviewer(s).

Genetically Related (Allelic) Disorders

OFD7, which includes unilateral cleft lip and hydronephrosis, has only been described in one mother-daughter pair, who were later found to have a mutation in OFD1; thus, this condition is either allelic to OFD1 or demonstrates variable expression of OFD1 [Nowaczyk et al 2003].

A family with X-linked Joubert syndrome and an isolated male with Joubert syndrome were found to have frameshift mutations in exon 21 of the OFD1 gene [Coene et al 2009].

An X-linked recessive syndrome associated with cognitive impairment, macrocephaly, and ciliary dysfunction is associated with a four-base duplication within the OFD1 gene, which led to a premature stop codon in exon 16 [Budny et al 2006].

Natural History

In addition to the findings described in Clinical Diagnosis, the following may be present in oral-facial-digital syndrome type I (OFD1):

Brain. Structural brain abnormalities may be accompanied by seizures and ataxia, especially in those with cerebellar atrophy.

Intellect. As many as 50% of individuals with OFD1 have some degree of intellectual disability, usually mild. Those with brain malformations are more likely to have intellectual disability, but the association is not consistent.

Oral manifestations. Hearing loss from recurrent otitis media, usually associated with cleft palate, has been reported. On occasion, speech and mastication can be affected.

Skin and hair. The hair is often described as dry, coarse, and brittle. Alopecia, usually partial, is an occasional finding. Alopecia has been described to follow the lines of Blaschko [Del C Boente et al 1999]. Milia, small keratinizing cysts, occur in at least 10%, and likely more, most often appearing on the scalp, ear pinnae, face, and dorsa of the hands. Milia are usually present in infancy and then resolve, but can then leave pitting scars.

Kidney. Although renal cysts have been reported as a prenatal finding [Nishimura et al 1999], the diagnosis is doubtful in these cases. Typically, cysts appear no earlier than late childhood. End-stage renal disease (ESRD) has been reported in affected girls and women ranging in age from 11 to 70 years. Recently it has been emphasized that the risk for significant renal disease appears to be higher than 60% after age 18 years [Prattichizzo et al 2008, Saal et al 2009]. In addition, liver and pancreatic cysts may be observed, but only in those who have renal cysts as well.

Other. Rare manifestations include short stature, choanal atresia, tibial pseudarthrosis, and berry aneurysms.

Almost all affected individuals with OFD1 are female; however, a few affected males have been reported. In most cases, these males are described as malformed fetuses delivered by women with OFD1; however, a male described by Goodship et al [1991] survived to term and expired on the first day of life. Virtually all reported males are simplex cases (i.e., a single occurrence in a family); the certainty of the diagnosis is thus unknown. Some of the other reported males with suspected OFD1 may in fact have other diagnoses, such as another OFD or Meckel-Gruber syndrome. It is theoretically possible (though highly unlikely) for an affected male to survive birth. Phenotypic variability is often seen in affected females, possibly as a result of random X-chromosome inactivation [Morleo & Franco 2008].

Genotype-Phenotype Correlations

There is some evidence that genotype-phenotype correlation exists:

• According to Thauvin-Robinet et al [2006], renal cysts appear to be correlated with splice mutations. Saal et al [2009], however, did not find this correlation.

• High-arched/cleft palate was found most frequently with missense and splice site mutations [Prattichizzo et al 2008].

• Intellectual disability is more often associated with mutations in exons 3, 8, 9, 13, and 16.

• Anomalous teeth are more often found in those with mutations in coiled coil domains.

Penetrance

OFD1 appears to be highly penetrant, although highly variable in expression. In some reports, renal cysts are the only apparent manifestation in affected women [McLaughlin et al 2000].

Anticipation

No evidence for anticipation exists.

Nomenclature

OFD1 was previously called Papillon-Léage-Psaume syndrome.

Prevalence

Estimates range from 1:250,000 to 1:50,000.

Evaluations Following Initial Diagnosis

To establish the extent of disease in an individual diagnosed with oral-facial-digital syndrome type I (OFD1), the following evaluations are recommended:

• Examination of the face, especially the mouth, and the hands for characteristic anomalies

• Formal, age-appropriate assessment of development

• Blood pressure and serum creatinine concentration

• Urinalysis, serum chemistries, and ultrasound evaluation of the kidneys, liver, and pancreas for cysts if the individual is age ten years or older

Treatment of Manifestations

• Cosmetic or reconstructive surgery for clefts of the lip and/or palate, tongue nodules, and accessory frenulae; treatment as for isolated cleft palate, including speech therapy and assessment for and aggressive treatment of otitis media

• Removal of accessory teeth

• Orthodontia for malocclusion

• Surgery to repair syndactyly, if present

• Routine management of renal disease, which may require hemodialysis or peritoneal dialysis and renal transplantation

• Routine management of seizures

• Special educational evaluation and input to address learning disabilities and other cognitive impairments

Surveillance

• Regular follow-up for assessment of speech and ear infections/hearing loss if cleft lip is present

• Annual determination of blood pressure and serum creatinine concentration to monitor renal function

• Annual assessment of renal function with follow-up by renal ultrasound evaluation to assess cyst development if abnormalities are detected

Testing of Relatives at Risk

Molecular testing of daughters of known gene carriers, even in the absence of oral, facial, and digital anomalies, may be reasonable.

Similarly, mothers of affected daughters could benefit from testing to determine if they are at risk for renal disease.

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

Therapies Under Investigation

Search ClinicalTrials.gov 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.

Other

Genetics clinics, staffed by genetics professionals, provide information for individuals and families regarding the natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information about available consumer-oriented resources. See the GeneTests Clinic Directory.

See Consumer Resources for disease-specific and/or umbrella support organizations for this disorder. These organizations have been established for individuals and families to provide information, support, and contact with other affected individuals.

Mode of Inheritance

Oral-facial-digital syndrome type I (OFD1) is inherited in an X-linked dominant manner.

Risk to Family Members

Parents of a proband

• Approximately 25% of females diagnosed with OFD1 have an affected mother.

• A female proband with OFD1 may have the disorder as the result of a de novo gene mutation. Approximately 75% of affected females are simplex cases (i.e., occurrence of OFD1 in a single family member) [Feather et al 1997, Macca & Franco 2009].

• Recommendations for the evaluation of the mother of a proband with an apparent de novo mutation include clinical evaluation and molecular genetic testing if the mutation in the proband has been identified. If the mother meets the diagnostic criteria for OFD1 or if she has another affected relative, she is an obligate carrier of an OFD1 gene mutation.

Sibs of a proband

• The risk to sibs depends on the genetic status of the mother.

• When the mother of an affected female is also affected, the risk to sibs of inheriting the disease-causing OFD1 allele at conception is 50%; however, most male conceptuses with the disease-causing OFD1 allele miscarry [Macca & Franco 2009]. Thus, at delivery the expected sex ratio of offspring is: 33% unaffected females; 33% affected females; 33% unaffected males.

• If no family history of OFD1 exists, the risk that the unaffected mother of an affected female will give birth to another female with OFD1 is less than 1%. Two possibilities account for this small increased risk: (1) a new mutation in a second child or (2) germline mosaicism in a parent [Nishimura et al 1999]. Although germline mosaicism has not been reported, it remains a possibility.

Offspring of a proband. The risk to the offspring of females with OFD1 must take into consideration the presumed lethality to affected males during gestation. At conception, the risk that the disease-causing OFD1 allele will be transmitted is 50%; however, most male conceptuses with the disease-causing OFD1 allele miscarry. Thus, at delivery the expected sex ratio of offspring is: 33% unaffected females; 33% affected females; 33% unaffected males.

Other family members of a proband. The risk to other family members depends on the status of the proband's mother. If the mother is affected, her family members could be at risk.

Related Genetic Counseling Issues

Specific risk issues. Males described as having OFD1 have been reported. As virtually all are simplex cases (i.e., a single occurrence in a family), the certainty of the diagnosis is unknown. It is theoretically possible for an affected male to be born alive, though this would be exceedingly rare. One family with a peculiar inheritance pattern has been described. In this pedigree, a woman with OFD1 had four unaffected sons, three of whom then had daughters all affected with OFD1.

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 young adults who are affected or at risk of being carriers.

Ascertainment of affected individuals. Often, mildly affected female relatives are diagnosed only after the identification of a severely affected individual [Thauvin-Robinet et al 2001].

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, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals. See for a list of laboratories offering DNA banking.

Prenatal Testing

Molecular genetic testing. Prenatal diagnosis for pregnancies at increased risk is possible by analysis of DNA extracted from fetal cells obtained by amniocentesis usually performed at about 15 to 18 weeks’ gestation or chorionic villus sampling (CVS) at about ten to 12 weeks’ gestation. The disease-causing allele must be identified before prenatal testing can be performed.

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Ultrasound examination

• High-risk pregnancies. In pregnancies of a female with OFD1, which are at 50% risk, prenatal ultrasound examination may detect structural brain malformations such as porencephaly [Shipp et al 2000, Thauvin-Robinet et al 2001] and/or duplicated hallux.

• Low-risk pregnancies. In pregnancies not known to be at increased risk for OFD1, the findings of structural brain anomalies and unilateral polydactyly of the great toe (hallucal duplication) should lead to consideration of OFD1. In such instances, it is appropriate to evaluate the mother for manifestations of OFD1.

Preimplantation genetic diagnosis (PGD) may be available for families in which the disease-causing mutation has been identified. For laboratories offering PGD, see .

Note: It is the policy of GeneReviews to include clinical uses of testing available from laboratories listed in the GeneTests Laboratory Directory; inclusion does not necessarily reflect the endorsement of such uses by the author(s), editor(s), or reviewer(s).

Literature Cited

1. al-Qattan MM. Cone-shaped epiphyses in the toes and trifurcation of the soft palate in oral-facial-digital syndrome type-I. Br J Plast Surg. 1998;51:476–9. [PubMed: 9849370]
2. al-Qattan MM, Hassanain JM. Classification of limb anomalies in oral-facial-digital syndromes. J Hand Surg Br. 1997;22:250–2. [PubMed: 9149999]
3. Budny B, Chen W, Omran H, Friegauf M, Tzschach A, Wisniewska M, Jensen LR, Raynaud M, Shoichet SA, Badura M, Lenzner S, Latos-Bielenska A, Ropers HH. A novel X-linked recessive mental retardation syndrome comprising macrocephaly and ciliary dysfunction is allelic to oral-facial-digital type I syndrome. Hum Genet. 2006;120:171–8. [PubMed: 16783569]
4. Coene KLM, Roepman R, Doherty D. OFD1 is mutated in X-linked Joubert syndrome and interacts with LCA5- encoded lebercilin. Am J Hum Genet. 2009;85:465–81. [PMC free article: PMC2756557] [PubMed: 19800048]
5. Coll E, Torra R, Pascual J, Botey A, Ara J, Perez L, Ballesta F, Darnell A. Sporadic orofaciodigital syndrome type I presenting as end-stage renal disease. Nephrol Dial Transplant. 1997;12:1040–2. [PubMed: 9175067]
6. de Conciliis L, Marchitiello A, Wapenaar MC, Borsani G, Giglio S, Mariani M, Consalez GG, Zuffardi O, Franco B, Ballabio A, Banfi S. Characterization of Cxorf5 (71-7A), a novel human cDNA mapping to Xp22 and encoding a protein containing coiled-coil alpha-helical domains. Genomics. 1998;51:243–50. [PubMed: 9722947]
7. Del C, Boente M, Primc N, Veliche H, Rosales S, Carrero-Valenzuela R, Saleme C, Asial R. A mosaic pattern of alopecia in the oral-facial-digital syndrome type I (Papillon-Léage and psaume syndrome). Pediatr Dermatol. 1999;16:367–70. [PubMed: 10571835]
8. Feather SA, Winyard PJ, Dodd S, Woolf AS. Oral-facial-digital syndrome type 1 is another dominant polycystic kidney disease: clinical, radiological and histopathological features of a new kindred. Nephrol Dial Transplant. 1997;12:1354–61. [PubMed: 9249769]
9. Ferrante MI, Giorgio G, Feather SA, Bulfone A, Wright V, Ghiani M, Selicorni A, Gammaro L, Scolari F, Woolf AS, Sylvie O, Bernard L, Malcolm S, Winter R, Ballabio A, Franco B. Identification of the gene for oral-facial-digital type I syndrome. Am J Hum Genet. 2001;68:569–76. [PMC free article: PMC1274470] [PubMed: 11179005]
10. Ferrante MI, Zullo A, Barra A, Bimonte S, Messaddeq N, Studer M, Dolle P, Franco B. Oral-facial-digital type I protein is required for primary cilia formation and left-right axis specification. Nat Genet. 2006;38(1):112–7. [PubMed: 16311594]
11. Goodship J, Platt J, Smith R, Burn J. A male with type I orofaciodigital syndrome. J Med Genet. 1991;28:691–4. [PMC free article: PMC1017056] [PubMed: 1941964]
12. Macca M, Franco B. The molecular basis of oral-facial-digital syndrome, type 1. Am J Med Genet C Semin Med Genet. 2009;151C(4):318–25. [PubMed: 19876934]
13. McLaughlin K, Neilly JB, Fox JG, Boulton-Jones JM. The hypertensive young lady with renal cysts--it is not always polycystic kidney disease. Nephrol Dial Transplant. 2000;15:1245–7. [PubMed: 10910455]
14. Morisawa T, Yagi M, Surono A, Yokoyama N, Ohmori M, Terashi H, Matsuo M. Novel double-deletion mutations of the Ofd1 gene creating multiple novel transcripts. Hum Genet. 2004;115:97–103. [PubMed: 15221448]
15. Morleo M, Franco B. Dosage compensation of the mammalian X-chromosome influences the phenotypic variability of X-linked dominant male-lethal disorders. J Med Genet. 2008;45:401–8. [PubMed: 18463129]
16. Nishimura G, Kuwashima S, Kohno T, Teramoto C, Watanabe H, Kubota T. Fetal polycystic kidney disease in oro-facio-digital syndrome type I. Pediatr Radiol. 1999;29:506–8. [PubMed: 10398784]
17. Nowaczyk MJ, Zeesman S, Whelan DT, Wright V, Feather SA. Oral-facial-digital syndrome VII is oral-facial-digital syndrome I: a clarification. Am J Med Genet. 2003;123A:179–82. [PubMed: 14598343]
18. Prattichizzo C, Macca M, Novelli V, Giorgio G, Barra A, Franco B. Mutational spectrum of the oral-facial-digital type I syndrome: a study on a large collection of patients. Hum Mutat. 2008;29(10):1237–46. [PubMed: 18546297]
19. Rakkolainen A, Ala-Mello S, Kristo P, Orpana A, Jarvela I. Four novel mutations in the OFD1 (Cxorf5) gene in Finnish patients with oral-facial-digital syndrome 1. J Med Genet. 2002;39:292–6. [PMC free article: PMC1735103] [PubMed: 11950863]
20. Romio L, Wright V, Price K, Winyard PJ, Donnai D, Porteous ME, Franco B, Giorgio G, Malcolm S, Woolf AS, Feather SA. OFD1, the gene mutated in oral-facial-digital syndrome type 1, is expressed in the metanephros and in human embryonic renal mesenchymal cells. J Am Soc Nephrol. 2003;14:680–9. [PubMed: 12595504]
21. Saal S, Faivre L, Aral B. Renal insufficiency, a frequent complication with age in oral-facial-digital syndrome type I. Clin Genet. 2009;77:258–65. [PubMed: 19817772]
22. Scolari F, Valzorio B, Carli O, Vizzardi V, Costantino E, Grazioli L, Bondioni MP, Savoldi S, Maiorca R. Oral-facial-digital syndrome type I: an unusual cause of hereditary cystic kidney disease. Nephrol Dial Transplant. 1997;12:1247–50. [PubMed: 9198060]
23. Shipp TD, Chu GC, Benacerraf B. Prenatal diagnosis of oral-facial-digital syndrome, type I. J Ultrasound Med. 2000;19:491–4. [PubMed: 10898304]
24. Stoll C, Sauvage P. Long-term follow-up of a girl with oro-facio-digital syndrome type I due to a mutation in the OFD 1 gene. Ann Genet. 2002;45:59–62. [PubMed: 12119212]
25. Thauvin-Robinet C, Franco B, Saugier-Veber P, Aral B, Gigot N, Donzel A, Van Maldergem L, Bieth E, Layet V, Mathieu M, Teebi A, Lespinasse J, Callier P, Mugneret F, Lasurel-Paulet A, Gautier E, Huet F, Teyssier JR, Tosi M, Frebourg T, Faivre L. Genomic deletions of OFD1 account for 23% of oral-facial-digital type 1 syndrome after negative DNA sequencing. Hum Mutat. 2009;30:E320–9. [PubMed: 19023858]
26. Thauvin-Robinet C, Cossee M, Cormier-Daire V, Van Maldergem L, Toutain A, Alembik Y, Bieth E, Layet V, Parent P, David A, Goldenberg A, Mortier G, Heron D, Sagot P, Bouvier AM, Huet F, Cusin V, Donzel A, Devys D, Teyssier JR, Faivre L. Clinical, molecular, and genotype-phenotype correlation studies from 25 cases of oral-facial-digital syndrome type 1: a French and Belgian collaborative study. J Med Genet. 2006;43:54–61. [PMC free article: PMC2564504] [PubMed: 16397067]
27. Thauvin-Robinet C, Rousseau T, Durand C, Laurent N, Maingueneau C, Faivre L, Sagot P, Nivelon-Chevallier A. Familial orofaciodigital syndrome type I revealed by ultrasound prenatal diagnosis of porencephaly. Prenat Diagn. 2001;21:466–70. [PubMed: 11438951]

Suggested Reading

1. Franco B. The molecular basis of oral-facial-digital type 1 (OFD1) syndrome. In: Epstein JC, Erickson RP, Wynshaw-Boris A, eds. Inborn Errors of Development. 2 ed. Vol 1. New York: Oxford University Press; 2008:1379-86.
2. Odent S, Le Marec B, Toutain A, David A, Vigneron J, Treguier C, Jouan H, Milon J, Fryns JP, Verloes A. Central nervous system malformations and early end-stage renal disease in oro-facio-digital syndrome type I: a review. Am J Med Genet. 1998;75:389–94. [PubMed: 9482645]

Author History

Brunella Franco, MD (2010-present)
Danilo Moretti-Ferreira, PhD; São Paulo State University, Brazil (2002-2010)
Izolda Nunes Guimaraes, PhD; São Paulo State University, Brazil (2002-2010)
Helga V Toriello, PhD (2002-present)

Revision History

• 14 October 2010 (me) Comprehensive update posted live

• 9 March 2007 (ht, cd) Revision: sequence analysis and prenatal diagnosis clinically available

• 14 August 2006 (me) Comprehensive update posted to live Web site

• 29 June 2004 (me) Comprehensive update posted to live Web site

• 24 July 2002 (me) Review posted to live Web site

• 27 February 2002 (ht) Original submission