Oro-facio-digital syndromes (OFDS) are a heterogenous group of rare developmental disorders characterized by oral, facial and digital anomalies. Other organ systems can be involved, defining specific types of OFDS. Research have identified at least 14 potential forms of oral-facial-digital syndrome classified by their patterns of signs and symptoms along with few unclassified forms. With the exception of OFD types I and VIII, which are X-linked, the majority of OFDS is transmitted as an autosomal recessive syndrome.[i] Mohr Syndrome or OFDS type II is characterized by:[ii] [iii] [iv] [v] [viii]
- Oral and facial features: frontal bossing, facial asymmetry, ocular hypertelorism, anti-mongoloid slant, broad nasal bridge, bifid nasal tip, cleft upper lip, cleft palate, lobulated tongue, thick frenulum and low set ears
- Digital anomalies: clinodactyly, syndactyly, brachydactyly, Y-shaped median metacarpals, pre- and post-axial polydactyly and duplication of the first toe
- CNS features: microcephaly, porencephaly, choroidal coloboma, internal hydrocephalus and cerebellar atrophy
- Other systemic features: conductive hearing loss, congenital heart defects (atrioventricular canal and endocardial cushion defects), scoliosis, pectus-excavatum, short stature and muscular hypotonia
Though nervous system defects may cause mental impairment, most patients are of normal intelligence.[vi] Cases of Mohr syndrome with Dandy-walker malformation have also been reported.[vii] The diagnosis is generally made on the basis of the clinical symptoms presented. The molecular genetics behind the disease is yet to be known.
Back in 1941, Norwegian geneticist and researcher Otto Lous Mohr published a report of a boy among 4 male siblings who had abnormalities of the tongue, face and digits while the parents and 3 other siblings were normal. Hence, Mohr suggested that the condition might be inherited as X-linked. Again in 1946, Claussen studied an affected male cousin of these boys, who had consanguineous parents, and suggested the inheritance to be autosomal recessive which was further supported by the study of other researchers.[x] The eponymous syndrome, “Mohr syndrome” or “Mohr-Claussen syndrome” was later renamed as “Orofaciodigital syndrome II (OFDS II)”. Rimoin and Edgerton (1967) suggested that Mohr syndrome might be called the oral-facial-digital syndrome II.[xi]
Less than 20 cases have been reported so far and the prevalence is less than 1/1000000.[viii]
It can be difficult to distinguish OFD II from OFD I. Features common to both ODF I and II are tongue hamartomas, spatulate, bifid or crenated tongue, midline clefts of the lip, hypertrophic frenula, cleft secondary palate, syndactyly, polydactyly, brachydactyly, mental deficiency and dystopia canthorium and broad nasal root. Features unique to OFD I are its X-linked dominant inheritance (affects female only), partial agenesis of corpus callosum and polycystic kidney disease. Features of OFD II that helps to distinguish it from ODF I are its’ autosomal recessive inheritance (affects male and female), bilateral reduplication of halluces, bilateral polysyndactyly, conductive hearing loss and choroidal coloboma.[ix]
[i] Franco, B., & Thauvin-Robinet, C. (2016). Update on oral-facial-digital syndromes (OFDS). Cilia, 5, 12. http://doi.org/10.1186/s13630-016-0034-4
[ii] Ghossaini SN, Hadi U, Tawil A. Oral-facial-digital syndrome type II variant associated with congenital tongue lipoma. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:324-327 3.
[iii] Biswas AA, Ghosh JKJ, Sinha MKRM, Basu KK, Chatterjee SS. Mohr-Claussen syndrome or oro-facial-digital syndrome (OFDS) type-II. J Pak Med Assoc 2009;59:484-486 4.
[iv] Naiboglu B, Oysu C, Gokceer T. Orofaciodigital syndrome. Ear Nose Throat J 2012;91:E8-E9
[v] Orofaciodigital syndrome 2. (n.d.). Retrieved November 04, 2017, from https://rarediseases.info.nih.gov/diseases/3701/orofaciodigital-syndrome-2
[vi] Wynbrandt, J., & Ludman, M. D. (2008). The encyclopedia of genetic disorders and birth defects. New York: Facts On File.
[vii] Haumont D, Pelc S. The Mohr syndrome: are there two variants? Clin Genet. 1983 Jul;24(1):41-6. Review. PubMed PMID: 6352094.
[viii] RESERVED I. Orphanet: Orofaciodigital syndrome type 2 [Internet]. Orpha.net. 2017 [cited 10 November 2017]. Available from: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=2751
[ix] Fenton OM, Watt-Smith SR. The spectrum of the oro-facial digital syndrome. Br J Plast Surg. 1985 Oct;38(4):532-9. PubMed PMID: 4052714.
[x] Beighton, P., & Beighton, G. (1986). The man behind the syndrome. Berlin: Springer-Verlag.
[xi] Rimoin, D. L., Edgerton, M. T. Genetic and clinical heterogeneity in the oral-facial-digital syndromes. J. Pediat. 71: 94-102, 1967.
is an MD in Pediatrics (IOM) and a Fellow in Neonatology (GRIPMER). He often writes his views online as well as share few important topics for medical students, doctors and specially parents. He has shared few of his experiences in Epomedicine which might be worthy of a reading. He does research in Pediatrics.