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Orofacial-digital syndrome IV(OFD4)

MedGen UID:
98358
Concept ID:
C0406727
Disease or Syndrome
Synonyms: Baraitser-Burn syndrome; MOHR-MAJEWSKI SYNDROME; OFD syndrome 4; OFD syndrome with tibial defects; OFD SYNDROME, BARAITSER-BURN TYPE; OFD4; OFDS 4; OFDS IV; Oral-facial-digital syndrome type 4; ORAL-FACIAL-DIGITAL SYNDROME, TYPE IV; Orofaciodigital syndrome 4; Orofaciodigital syndrome IV; Orofaciodigital syndrome with tibial dysplasia
SNOMED CT: OFD IV - Orofacial-digital syndrome IV (239031000); Orofacial-digital syndrome IV (239031000); Orofaciodigital syndrome type 4 (239031000); Oral-facial-digital syndrome type 4 (239031000); Baraitser Burn syndrome (239031000); Mohr Majewski syndrome (239031000)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): TCTN3 (10q24.1)
 
Monarch Initiative: MONDO:0009794
OMIM®: 258860
Orphanet: ORPHA2753

Definition

Oral-facial-digital syndrome is actually a group of related conditions that affect the development of the oral cavity (the mouth and teeth), facial features, and digits (fingers and toes).

Researchers have identified at least 13 potential forms of oral-facial-digital syndrome. The different types are classified by their patterns of signs and symptoms. However, the features of the various types overlap significantly, and some types are not well defined. The classification system for oral-facial-digital syndrome continues to evolve as researchers find more affected individuals and learn more about this disorder.

The signs and symptoms of oral-facial-digital syndrome vary widely. However, most forms of this disorder involve problems with development of the oral cavity, facial features, and digits. Most forms are also associated with brain abnormalities and some degree of intellectual disability.

Abnormalities of the oral cavity that occur in many types of oral-facial-digital syndrome include a split (cleft) in the tongue, a tongue with an unusual lobed shape, and the growth of noncancerous tumors or nodules on the tongue. Affected individuals may also have extra, missing, or defective teeth. Another common feature is an opening in the roof of the mouth (a cleft palate). Some people with oral-facial-digital syndrome have bands of extra tissue (called hyperplastic frenula) that abnormally attach the lip to the gums.

Other features occur in only one or a few types of oral-facial digital syndrome. These features help distinguish the different forms of the disorder. For example, the most common form of oral-facial-digital syndrome, type I, is associated with polycystic kidney disease. This kidney disease is characterized by the growth of fluid-filled sacs (cysts) that interfere with the kidneys' ability to filter waste products from the blood. Other forms of oral-facial-digital syndrome are characterized by neurological problems, particular changes in the structure of the brain, bone abnormalities, vision loss, and heart defects.

Distinctive facial features often associated with oral-facial-digital syndrome include a split in the lip (a cleft lip); a wide nose with a broad, flat nasal bridge; and widely spaced eyes (hypertelorism).

Abnormalities of the digits can affect both the fingers and the toes in people with oral-facial-digital syndrome. These abnormalities include fusion of certain fingers or toes (syndactyly), digits that are shorter than usual (brachydactyly), or digits that are unusually curved (clinodactyly). The presence of extra digits (polydactyly) is also seen in most forms of oral-facial-digital syndrome. [from MedlinePlus Genetics]

Clinical features

From HPO
Hand polydactyly
MedGen UID:
510636
Concept ID:
C0158733
Congenital Abnormality
A kind of polydactyly characterized by the presence of a supernumerary finger or fingers.
Foot polydactyly
MedGen UID:
510637
Concept ID:
C0158734
Congenital Abnormality
A kind of polydactyly characterized by the presence of a supernumerary toe or toes.
Postaxial polydactyly
MedGen UID:
67394
Concept ID:
C0220697
Congenital Abnormality
Polydactyly refers to the occurrence of supernumerary digits and is the most frequent of congenital hand and foot deformities. Based on the location of the extra digits, polydactyly can be classified into preaxial, involving the thumb or great toe; postaxial, affecting the fifth digit; and central, involving the 3 central digits. Postaxial polydactyly (PAP) is further subclassified into 2 types: in type A, a well-formed extra digit articulates with the fifth or a sixth metacarpal, whereas in type B, a rudimentary, poorly developed extra digit is present (summary by Umm-e-Kalsoom et al., 2012). Genetic Heterogeneity of Postaxial Polydactyly Other forms of postaxial polydactyly type A include PAPA2 (602085) on chromosome 13q21; PAPA3 (607324) on chromosome 19p13; PAPA4 (608562) on chromosome 7q22; PAPA5 (263450) on chromosome 13q13; PAPA6 (615226), caused by mutation in the ZNF141 gene (194648) on chromosome 4p16; PAPA7 (617642), caused by mutation in the IQCE gene (617631) on chromosome 7p22; PAPA8 (618123), caused by mutation in the GLI1 gene (165220) on chromosome 12q13; PAPA9 (618219), caused by mutation in the CIBAR1 gene (617273) on chromosome 8q22; and PAPA10 (618498), caused by mutation in the KIAA0825 gene (617266) on chromosome 5q15.
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Toe syndactyly
MedGen UID:
75581
Concept ID:
C0265660
Congenital Abnormality
Webbing or fusion of the toes, involving soft parts only or including bone structure. Bony fusions are referred to as "bony" Syndactyly if the fusion occurs in a radio-ulnar axis. Fusions of bones of the toes in a proximo-distal axis are referred to as "Symphalangism".
Short finger
MedGen UID:
334977
Concept ID:
C1844548
Anatomical Abnormality
Abnormally short finger associated with developmental hypoplasia.
Short tibia
MedGen UID:
338005
Concept ID:
C1850259
Finding
Underdevelopment (reduced size) of the tibia.
Clinodactyly
MedGen UID:
1644094
Concept ID:
C4551485
Congenital Abnormality
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Hamartoma of tongue
MedGen UID:
98465
Concept ID:
C0431565
Finding
A benign (noncancerous) tumorlike malformation made up of an abnormal mixture of cells and tissues that originates in the tongue.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Porencephalic cyst
MedGen UID:
906044
Concept ID:
C4082172
Disease or Syndrome
A cavity within the cerebral hemisphere, filled with cerebrospinal fluid, that communicates directly with the ventricular system.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Tongue nodules
MedGen UID:
116122
Concept ID:
C0241438
Finding
Lobulated tongue
MedGen UID:
140914
Concept ID:
C0431564
Congenital Abnormality
Multiple indentations and/or elevations on the edge and/or surface of the tongue producing an irregular surface contour.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Accessory oral frenulum
MedGen UID:
867439
Concept ID:
C4021814
Congenital Abnormality
Extra fold of tissue extending from the alveolar ridge to the inner surface of the upper or lower lip.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVOrofacial-digital syndrome IV
Follow this link to review classifications for Orofacial-digital syndrome IV in Orphanet.

Recent clinical studies

Etiology

Alamillo CL, Powis Z, Farwell K, Shahmirzadi L, Weltmer EC, Turocy J, Lowe T, Kobelka C, Chen E, Basel D, Ashkinadze E, D'Augelli L, Chao E, Tang S
Prenat Diagn 2015 Nov;35(11):1073-8. Epub 2015 Aug 3 doi: 10.1002/pd.4648. PMID: 26147564
Thomas S, Legendre M, Saunier S, Bessières B, Alby C, Bonnière M, Toutain A, Loeuillet L, Szymanska K, Jossic F, Gaillard D, Yacoubi MT, Mougou-Zerelli S, David A, Barthez MA, Ville Y, Bole-Feysot C, Nitschke P, Lyonnet S, Munnich A, Johnson CA, Encha-Razavi F, Cormier-Daire V, Thauvin-Robinet C, Vekemans M, Attié-Bitach T
Am J Hum Genet 2012 Aug 10;91(2):372-8. doi: 10.1016/j.ajhg.2012.06.017. PMID: 22883145Free PMC Article
Jank S, Kelderer HW, Raubenheimer EJ, Puelacher W
Int J Oral Maxillofac Surg 2008 Mar;37(3):296-9. Epub 2007 Nov 26 doi: 10.1016/j.ijom.2007.09.170. PMID: 18035522
Lesca G, Fallet-Bianco C, Plauchu H, Vitrey D, Verloes A, Attia-Sobol J
Am J Med Genet A 2006 Apr 1;140(7):757-63. doi: 10.1002/ajmg.a.31144. PMID: 16502430
Toriello HV
Am J Med Genet Suppl 1988;4:149-59. doi: 10.1002/ajmg.1320310515. PMID: 3144982

Diagnosis

Hussain S, Nawaz S, Khan H, Acharya A, Schrauwen I, Ahmad W, Leal SM
Ann Hum Genet 2022 Nov;86(6):291-296. Epub 2022 Aug 30 doi: 10.1111/ahg.12462. PMID: 36039988Free PMC Article
Mathai SS, Rajeev A, Sahu S
Indian J Pediatr 2011 Aug;78(8):1023-4. Epub 2011 Mar 22 doi: 10.1007/s12098-011-0387-z. PMID: 21424801
Rösing B, Kempe A, Berg C, Kahl P, Knöpfle G, Gembruch U, Geipel A
Ultrasound Obstet Gynecol 2008 Apr;31(4):457-60. doi: 10.1002/uog.5285. PMID: 18383484
Lesca G, Fallet-Bianco C, Plauchu H, Vitrey D, Verloes A, Attia-Sobol J
Am J Med Genet A 2006 Apr 1;140(7):757-63. doi: 10.1002/ajmg.a.31144. PMID: 16502430
Moerman P, Fryns JP
Genet Couns 1998;9(1):39-43. PMID: 9555586

Prognosis

Jank S, Kelderer HW, Raubenheimer EJ, Puelacher W
Int J Oral Maxillofac Surg 2008 Mar;37(3):296-9. Epub 2007 Nov 26 doi: 10.1016/j.ijom.2007.09.170. PMID: 18035522
Lesca G, Fallet-Bianco C, Plauchu H, Vitrey D, Verloes A, Attia-Sobol J
Am J Med Genet A 2006 Apr 1;140(7):757-63. doi: 10.1002/ajmg.a.31144. PMID: 16502430

Clinical prediction guides

Hussain S, Nawaz S, Khan H, Acharya A, Schrauwen I, Ahmad W, Leal SM
Ann Hum Genet 2022 Nov;86(6):291-296. Epub 2022 Aug 30 doi: 10.1111/ahg.12462. PMID: 36039988Free PMC Article

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