Handbook of Genetic Counseling/Oral-Facial-Digital Syndrome – Sort 1

Handbook of Genetic Counseling/Oral-Facial-Digital Syndrome - Type 1
December 18, 2020 0 Comments

Oral-Facial-Digital Syndrome – Sort 1

Introduction and Contracting[edit]

  • What’s your understanding about why Dr. wished to observe up with ____in our genetics clinic?
  • What do you already learn about OFD syndrome?
  • Do you’ve gotten any questions you desire to us to handle at present?
  • What’s your most important concern?
  • Define the go to
  • I’ve slightly household historical past data from when Dr. visited ____ within the hospital, however I’ll take a extra detailed household historical past.
  • I may even receive slightly extra details about _______’s medical historical past
  • Dr. will are available in to look at _____ and he’ll in all probability need to check out a few of the options that you simply (her mom) share with ________.
  • We are going to then focus on the analysis of OFD1 together with the inheritance, and points concerning the medical administration.


  • The analysis of OFD1 is established by scientific findings
  • Established at delivery in some infants as a result of mixture of oral, facial, and digital anomalies
  • In others it’s suspected solely after polycystic kidney illness is recognized (often in later childhood or maturity)
  • In some it’s only urged after a girl has an affected youngster.

Attribute Options[edit]


  • tongue is lobed (bifid or trifid)
  • tongue nodules (often hamartomas or lipomas) happen in no less than a 3rd of these with OFD1
  • ankyloglossia is frequent (partial or full fusion of the tongue to the underside of the mouth) attributable to a brief lingual frenulum
  • Cleft exhausting or taste bud, submucous cleft palate, or extremely arched palate happen in over half of sufferers
  • Trifurcation of the taste bud has been reported
  • Alveolar clefts and accent gingival frenulae are frequent (these fibrous bands are hyperplastic frenulae extending from the buccal mucous membrane to the alveolar ridge, leading to notching of the alveolar ridges)
  • Dental abnormalities embody lacking tooth (most typical), additional tooth, enamel dysplasia, and malocclusion


  • Ocular hypertelorism or telecanthus happens in no less than 33%
  • Hypoplasia of the alae nasi, median cleft lip or pseudocleft higher lip, and micrognathia are frequent (precise frequencies unknown )


  • brachydactyly (brief digits), syndactyly (fused digits) of various levels, and clinodactyly (inward curvature) of the fifth finger are all frequent
  • different fingers, notably the third (i.e., center finger) might present variable radial or ulnar deviation
  • duplicated hallux (nice toe) happens in lower than half of sufferers and is often unilateral
  • preaxial or postaxial polydactyly of the palms (1-2% of sufferers)
  • Radiographs of the palms typically exhibit nice reticular radiolucencies, described as irregular mineralization of the bone, with or with out spicule formation of the phalanges


  • Structural mind abnormalities happen in 10-15% (could also be an underestimate)
  • most typical embody
    • intracerebral cysts
    • agenesis of the corpus callosum
    • cerebellar agenesis with or with out Dandy-Walker malformation
  • Different reported anomalies have every been described in just a few sufferers
    • sort 2 porencephaly (schizencephalic porencephaly)
    • pachygyria (abnormally giant convolutions of cerebral cortex) and heterotopias (displacement of grey matter sometimes into the white matter)
    • hydrocephalus
    • cerebral or cerebellar atrophy


  • polycystic kidney illness (unknown frequency) fewer than 50%
  • age of onset most frequently maturity (however have been described in youngsters)


  • As many as half of the people with OFD1 have a point of psychological retardation, which is often delicate
  • Relies upon partly on mind abnormalities, however not all the time constant
  • Extreme psychological retardation within the absence of mind malformations seems to be uncommon


  • Uncommon manifestations embody choanal atresia, tibial pseudarthrosis, and berry aneurysms
  • Hair is commonly described as dry, coarse, and brittle
  • Alopecia (absence of hair), often partial, is an occasional discovering
  • Milia, small keratinizing cysts, happen in no less than 10% (however seemingly extra) happen most frequently on the scalp, ear pinnae, face, and dorsa of the palms
  • milia are often current in infancy after which resolve, however can then go away pitting scars


  • Estimates vary from 1/50,000 to 1/250,000


  • OFD1 is inherted in an X-linked dominant method
  • Nearly all affected people are feminine
  • experiences of males with OFD1
    • some males are described as malformed fetuses born to ladies with OFD1
    • normally the analysis is unsure as a result of the mom is unaffected
  • Roughly 75% of instances are sporadic (ought to study mom and take household historical past to find out this)

Caveats of inheritance[edit]

  • One household with a peculiar inheritance sample has been described. On this pedigree, a girl with OFDI had 4 unaffected sons, three of whom then had daughters all affected with OFDI
  • Typically, mildly affected feminine family are identified solely after the identification of a severely affected particular person

Recurrance dangers[edit]

  • If there is no such thing as a household historical past of OFD1, the danger that an unaffected mom of an affected feminine may have one other feminine with OFD1 is lower than 1% as a result of the potential of
    • 1) a brand new mutation in a second youngster
    • 2) germline mosaicism in a mother or father (extra seemingly than new mutation)
      • Germline mosaicism is when an individual unaffected by OFD1 has a number of copies of the OFD1 mutation of their gametes
      • Theoretically, germline mosaicism can happen in both mother or father of a feminine with OFD1
  • At conception, the danger to the offspring of females with OFD1 of inheriting the mutant OFD1 is 50% (most male conceptuses with the mutant OFD1 allele miscarry)
  • At supply the anticipated intercourse ratio of offspring is: 33% unaffected females; 33% affected females; 33% unaffected males

Recurrance is a misspelling. This could as a substitute be ‘Recurrence’

Genetic Testing[edit]

  • OFD1 is the one gene presently identified to be related to oral-facial-digital syndrome sort I
  • chromosomal locus Xp22.3-p22.2
  • Molecular genetic testing of the OFD1 gene is accessible on a analysis foundation solely
  • Examined in a restricted variety of sufferers
  • A wide range of mutations have been recognized, the bulk lead to untimely protein truncation
  • Detection price unknown

Molecular genetics[edit]

  • Regular allelic variants:
    • OFD1 has 23 exons
    • OFD1 is on the portion of the X chromosome that escapes inactivation
    • OFD1 was expressed in all grownup tissues that have been examined. Nevertheless, throughout early improvement, expression is completely within the genital ridges, quickly adopted by expression in craniofacial constructions and nervous system
    • Homologous genes embody Cyorf1 (Y chromosomes) and C5orf1 (chromosome 5)
  • Pathologic allelic variants:
    • Exonic and intronic mutations have each been described
    • Mutations in exons embody single base pair modifications, frameshifts, and deletions
    • These modifications have occurred to this point in exons 3, 11, 13, and 16 solely
    • Irregular splicing has additionally been reported in introns 4 and 5

Regular gene product[edit]

    • The protein OFD1 happens in two varieties, Cxorf5-1 and Cxorf5-2, that are differentiated by way of an alternate splice web site
    • Cxorf5-1 is a 1011 amino acid protein, whereas Cxorf5-2 is a 367 amino acid protein
    • The 2 proteins share the primary 351 amino acids; Cxorf5-2 then has a C-terminal area of 16 amino acids
    • The operate of the protein is unknown, however considered associated to a protein-protein interplay mechanism throughout improvement

Irregular gene product[edit]

  • Many of the mutations result in the untimely truncation of the protein and are subsequently thought to lead to a lack of operate
  • Since this gene is on the portion of the X chromosome that escapes inactivation, the truncated protein might work together with the wildtype product to supply a dominant-negative impact
  • No genotype-phenotype correlation exists to this point.

Prenatal testing[edit]

  • Prenatal testing utilizing molecular genetic methods will not be clinically obtainable
  • Prenatal ultrasound examination might detect structural mind malformations and duplicated hallux

Differential analysis[edit]

(consists of the opposite oral-facial-digital syndromes and issues together with cystic renal illness)

  • OFD II (Mohr syndrome)
    • Autosomal recessive
    • primarily distinguished by polydactyly (bilateral postaxial polydactyly of palms, bilateral polysyndactly of ft)
    • different manifestations embody broad (typically bifid) nasal tip
    • midline partial cleft of lip
    • these people would not have milia or polycystic kidney illness
  • OFD III (Sugarman syndrome)
    • Autosomal recessive
    • characterised by see-saw winking and polydactyly solely postaxial
    • myoclonic jerks (additionally happen)
    • bulbous nostril (can also happen)
    • apparently low set ears (additionally happen)
  • OFD IV (Buru-Baraister syndrome)
    • Autosomal recessive
    • tibial involvement (brief tibia) and pre and or postaxial polydactyly (major manifestations)
    • Different findings embody pectus excavatum and brief stature
  • OFD V (Thurston syndrome)
    • Autosomal recessive
    • consists of polydactyly and median cleft lip solely
    • Just one affected particular person has had hyperplastic frenula
  • OFD VI (Varadi-Papp syndrome)
    • distinguished by polydactyly (notably central) and cerebellar malformations
    • Renal agenesis and dysplasia have been described
  • OFD VII (Whelan syndrome)
    • consists of unilateral cleft lip and hydronephrosis
    • solely been described in a single mother-daughter pair
    • congenital hydronephrosis, coarse hair, facial asymmetry, facial weak spot, preauricular tags
    • Inheritance both autosomal or X-linked dominant
    • could also be allelic to OFD1 if X-linked dominant
    • apparently inherited as an X-linked recessive trait
    • mixture of polydactyly, tibial and radial defects, and epiglottal abnormalities
    • pre and postaxial polydactyly of hans and bilateral duplication of halluces, brief stature, bypoplasia of the epiglottis, absent/irregular central incisors, broad/bifid nasal tip
    • could also be allelic to OFD1
  • OFD IX
    • consists of retinal abnormalities and nonmedian cleft lip
    • reported in three males
  • Autosomal dominant polycystic kidney illness (ADPKD)
    • In ADPKD cysts develop from tubules, whereas in OFD1 cysts develop from each tubules and glomeruli
    • nonetheless, imaging research can’t all the time distinguish the renal cystic illness of OFD1 from that of ADPKD and different cystic renal issues
    • cysts are stated to be smaller and extra uniform in measurement in OFD1 than in ADPKD, and the kidneys should not as enlarged or deformed in OFD1
    • hepatic cysts and berry aneurysms have been noticed in OFD1
    • Different distinguishing options are mode of inheritance and the shortage of oral, facial, digital, or mind abnormalities in ADPKD
  • Meckel-Gruber syndrome
    • autosomal recessive situation characterised by the mix of encephalocele, polydactyly, and polycystic kidney illness
    • Different frequent findings embody microphthalmia (small eyes) or anophthalmia (no eyes), cleft lip/palate, hepatic fibrosis and cysts, and congenital cardiac defects

Well being issues and administration[edit]

  • Therapy for OFD1 is supportive
  • Elimination of accent tooth; orthodontia for malocculsion; and beauty or reconstructive surgical procedure for clefts of the lip and/or palate, tongue nodules, accent frenula, and syndactyly
  • Listening to loss from recurrent otitis media, often related to cleft palate, has been reported
  • Finish stage renal illness (ESRD) has been reported in affected women and girls ranging in age from 11 years to age 70 years
  • Administration of renal illness might require hemodialysis or peritoneal dialysis and renal transplantation.
  • Not too long ago it has been emphasised that the danger for important renal illness could also be better than beforehand reported
  • Liver and pancreatic cysts could also be noticed
  • Laboratory investigations similar to creatinine ranges and blood stress dedication to observe renal operate ought to be completed
  • if applicable, imaging research of the kidneys, liver, and pancreas ought to be carried out

Affected person Assets[edit]

(I discovered no affected person literature that I felt was good or applicable)

  • http://www.netnet.web/mums/ — Web site the place dad and mom are matched up in keeping with the situation that their youngster has. There are presently no less than 4 folks registered with OFD syndrome sort I and 15 simply listed below OFD syndrome.
  • American Cleft Palate-Craniofacial Affiliation
104 South Estes Drive, Suite 204
Chapel Hill, NC 27514
Cellphone: 919-933-9044
Fax: 919-933-9604
E mail: [email protected]
  • Nationwide Kidney Basis
30 East thirty third Avenue, Suite 1100
New York, NY 10016
Cellphone: 800-622-9010 or 212-889-2210
Fax: 212-689-9261
E mail: [email protected]


  • Geneclinics-Oral-facial-digital syndrome sort 1 (most data got here from this reference)
  • Smith’s Recognizable Sample’s of Inheritance. (p. 262-264) (detailed details about differential analysis)

The knowledge on this define was final up to date in 2002.

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