Orofaciodigital syndromes I and II

This is part of Rare diseases.

Diagnosis: Orofaciodigital syndromes I and II

Synonyms: Orol-facial-digital syndromes I and II, OFD I and II, Papillon-Léage-Psaume syndrome (OFD I), Mohr syndrome (OFD II)


Publication date: 2012-11-30
Version: 3.0

ICD 10 code

Q87.0G Orofaciodigital syndromes I
Q87.0 Orofaciodigital syndromes II

The disease

Orofaciodigital syndrome (OFD) is the collective name for a group of rare inherited syndromes characterised by malformations of the mouth (oris), face (facies), hands and feet (digitus = finger, toe). The Norwegian geneticist Otto J Mohr published the first case report describing this combination of symptoms in 1941, and the condition became known as Mohr syndrome (now known as OFD II). In 1954, the French dentists Jean Psaume and Éline Papillon-Léage described another OFD syndrome, now known as OFD I (Papillon-Léage-Psaume syndrome).

The disorders described in this material, OFD I and OFD II, are the most common OFD syndromes. They can be distinguished from each other with the help of skeletal X-rays, and by the observation of various specific symptoms, and they also have different patterns of inheritance. Currently, a further nine OFD syndromes have been identified. They are extremely rare and it may be difficult to distinguish among them. They are not described here.


The overall incidence is unknown, but it is estimated that approximately one child per 100,000 is born with some form of OFD. OFD I affects females only, as male foetuses with the syndrome die before birth. Approximately one in every 50,000 to 250,000 girls is born with OFD I. Only a few individuals with OFD II have been diagnosed in Sweden.


The cause of OFD is a genetic mutation. The cause of OFD 1, a single mutation on gene CXORF5, is the only one to have been identified to date. This gene is located on the short arm of the X chromosome (Xp22.3-22.2) and governs the production of (codes for) the protein OFD I. This protein is essential for foetal survival and for the early development of all organs that are malformed in cases of OFD I.


The inheritance pattern of OFD I is X-linked dominant. In most cases OFD I is caused by a new mutation. This means that the genetic mutation occurs in an individual for the first time and is not inherited from either parent. Consequently, parents with a child with a new mutation generally do not have an increased risk of having another child with the disorder. However, the new genetic mutation will be hereditary and an adult woman with this mutation risks passing on the mutated gene to her children. The pattern of inheritance is then X-linked dominant.

A woman who carries the mutated gene has a 50 per cent chance of passing it on to her children. Boys are not born with OFD I as male foetuses carrying the mutated gene die before birth, and these pregnancies result in spontaneous abortions. The reason is that the gene is critical to foetal development and the male foetus, having only one X chromosome, has none of the essential protein. As girls have two X chromosomes they fare better, for although one X chromosome is affected, the second X chromosome is normal.

Figur: Figure: X-linked dominant inheritance via a female carrier with the disease

In OFD II the pattern of inheritance is autosomal recessive. This means that both parents are healthy carriers of a mutated gene. In each pregnancy there is a 25 per cent risk that the child will inherit double copies of the mutated gene (one from each parent), in which case the child will have the disease. In 50 per cent of cases the child inherits only one mutated gene (from one parent only) and like both parents, will be a healthy carrier of the mutated gene. In 25 per cent of cases the child will not have the disease and will not be a carrier of the mutated gene.

Figure: Autosomal recessive inheritance

A person with an inherited autosomal recessive disease has two copies of the mutated gene. If this person has a child with a person who is not a carrier of the mutated gene, all the children will inherit the mutated gene but they will not have the disorder. If a person with an inherited autosomal recessive disease has children with a healthy carrier of the mutated gene (who has one mutated gene) there is a 50 per cent risk of the child having the disorder, and a 50 per cent risk of the child being a healthy carrier of the mutated gene.


Symptoms of OFD I and II vary, depending on which of the two syndromes is in question. Common symptoms include lip, jaw, palate and tongue clefts. Clefts related to the OFD syndromes have a characteristic appearance and are associated with multiple, abnormal folds of tissue which limit movement of the tongue and lips (frenulae). Individuals with the OFD syndromes may also have benign tumours on the tongue, a characteristic facial appearance, extra fingers or toes or webbing between fingers and toes, and develop tooth abnormalities. Brain abnormalities and delayed intellectual development are also common.


Girls with OFD I are born with oral, facial and digital abnormalities as well as brain abnormalities. Polycystic kidney disease is common, and distinguishes OFD I from the other OFD types, but symptoms usually do not present in childhood.

At birth children may have lip, palate or tongue clefts and a highly arched palate. Benign tumours (hamartoma or lipoma), affecting the front or sides of the tongue, and multiple tissue folds (multiple frenulae) are other signs of the syndrome. There may be missing teeth, extra teeth, or the teeth may have an abnormal appearance.

Girls with OFD I syndrome may have a characteristic appearance, with wide-set eyes (hypertelorism), different-size nostrils, a flat nose, and poorly developed cheekbones and lower jaw (micrognathia).

Hands are more frequently affected than feet. Short (brachydactyly), webbed fingers (syndactyly), or permanently curved fingers or toes (clinodactyly) are common. Less common are supernumerary fingers or toes (polydactyly). Irregular calcification affecting the bones of the hands and feet is specific to OFD I, and is not found in OFD II.

Approximately 50 per cent of girls with OFD I have brain abnormalities, including brain cysts or absent corpus callosum (the bundle of nerve fibres connecting the left and right brain hemispheres). There may also be cerebellar abnormalities, or the cerebellum may be missing.

It is estimated that 50 per cent of children with the syndrome have learning difficulties or mild intellectual disability. Severe intellectual disability may occur as a result of brain abnormalities. Individuals with intellectual disability require more time to understand and learn new skills. They may also have difficulties organising new information, adapting to new situations, and have trouble seeing how things or events relate to each other. Expressing their desires, thoughts or emotions may take longer than for other children.

Language development is often delayed in girls with OFD I, and speech difficulties are common.

Almost 50 per cent develop polycystic kidney disease, meaning that clusters of fluid-filled cysts develop in the kidneys. This distinguishes OFD I from other OFD syndromes. In most cases the onset of kidney disease occurs in adulthood, but cases of infantile kidney disease have been reported. Polycystic kidney disease may cause renal failure.

Hair and skin are also sometimes affected. Children may have dry, brittle hair, patches of hair loss (alocepia) and whiteheads (facial milias).


Children with OFD II (Mohr syndrome) are born with multiple abnormalities. Underdevelopment of the cerebellum, in particular in the midline lobe separating the brain hemispheres (hypoplasia of the vermis), is common.

Neonates may have an irregular breathing pattern, characterised by long pauses between breaths, interrupted by episodes of rapid breathing. They also have poor muscle tone (hypotonia).

The centre of the upper lip, and the tongue often display clefts. Other common symptoms include a cleft or highly-arched palate. Children may have multiple labial and lingual tissue folds (fraenula), but this symptom is less common than in OFD I. Tongue and lip movements may be restricted owing to short, wide frenulae. Teeth may be missing or wrongly positioned. A common symptom found on the front of the tongue is a type of benign, whitish, soft-tissue tumour (hamartoma or lipoma).

Individuals may also have a small head (microcephaly) and the forehead may have an abnormal shape. Many individuals also have a small jaw. Individuals with the syndrome often have wide-set eyes with epicanthal folds covering their inner corners.

Children with OFD II often have hearing loss due owing to impaired conductivity in the middle ear.

Children with OFD II often have extra fingers or toes, or webbing between fingers or toes. A common sign of the syndrome is a supernumerary big toe on both feet. Other skeletal abnormalities include abnormal curvature of the spine (scoliosis), and an abnormally shaped breastbone (pectus excavatum).

Children with OFD II may suffer from delayed motor development and balance problems. Some children have varying degrees of intellectual impairment.


The diagnosis is based on the observation of symptoms and a skeletal X-ray. DNA-based diagnostics can be used to confirm OFD I only. There is no specific diagnostic test for OFD II and it is diagnosed on the basis of a holistic view of all the symptoms and signs. Polycystic kidney disease presents only in OFD I while duplication of, or abnormally wide, big toes are characteristic of OFD II.

At the time of an OFD I diagnosis the family should be offered genetic counselling. Carrier and prenatal diagnostics, as well as pre-implantation genetic diagnostics (PGD) in association with IVF (in vitro fertilization), are available in families where the mutation is known.

In the case of OFD II, it is usually possible to diagnose the syndrome with the help of an ultrasound examination after week 16.


Treatment is directed at relieving the symptoms and commonly involves surgery. Children with suspected OFD should undergo extensive diagnostic investigations carried out by a paediatrician, an ENT (ear, nose and throat) specialist with experience in the area, and, if possible, a clinical geneticist. Computer tomography or magnetic resonance imaging is used to examine the nervous system. Ultrasonography is used to exclude polycystic kidney disease.

Investigations should also include developmental evaluations performed by a psychologist.


Children born with lip, palate or tongue clefts undergo early surgical intervention. Plastic surgery clinics have multidisciplinary teams (craniofacial teams and teams specialising in lip, jaw and palate clefts), with special routines for treatment and follow-up. These teams consist of a plastic surgeon, a speech therapist, a maxillofacial surgeon, an orthodontist and a psychologist. Oral tumours are surgically removed.

Palatal function is essential to speech and swallowing. It is important that a speech therapist follows the child’s language development in order to provide advice on how to stimulate speech. A speech therapist can also provide advice and support if the child finds it hard to eat and has swallowing difficulties.

Growth and development of the face and jaw should be monitored. Orthodontic treatment and maxillofacial surgery are often necessary. Children should have early contact with the dental services, preferably a pedodontist (paediatric dental specialist) for an assessment, as well as help with preventive care and information on oral hygiene.

Toe and finger abnormalities can be corrected surgically.

In cases of renal failure, dialysis is essential. There are two types of treatment: haemodialysis and peritoneal dialysis. In haemodialysis, blood is pumped out of the body and passes through a machine which cleans it and removes impurities before returning it to the body. Treatment takes approximately four hours and most individuals require three treatments a week. In peritoneal dialysis, the blood never leaves the body, but it is cleaned in the abdomen by the dialysis fluid while it circulates through the patient’s own peritoneum. Peritoneal dialysis can be carried out during sleep, in the patient’s home.

When there is no renal function, a kidney transplant is the usual treatment.


Abnormal breathing patterns should be investigated at a paediatric clinic with the help of a clinical physiologist, and special monitoring equipment may be used.

Clefts are operated on early, the surgery being performed by specialist teams at plastic surgery clinics. Orthodontic treatment and maxillofacial surgery are often necessary. Oral tumours are removed surgically.

It is important to have contact with a speech therapist who can give advice on ways to stimulate speech. A speech therapist can also provide advice and support if the child finds it hard to eat and has swallowing difficulties. There should be early contact with the dental services, where a dentist can provide advice on oral hygiene and preventive treatments.

There is an increased risk of recurrent ear infection when the child has a cleft palate. Regular appointments with an ear-nose-throat specialist are recommended to prevent persistent ear problems. Children with hearing impairments often require auditory habilitation measures, which may include hearing aids and other technical devices (see below under “Habilitation”). Collaboration between ENT specialists, plastic surgeons and the hearing care services is important.

Webbed or extra toes or fingers are corrected surgically, both for cosmetic reasons and in order to optimise functionality. Special shoes may be needed to facilitate walking.


Depending on the degree of disability, some of these children require contact with a habilitation team including professionals with special expertise in how disability affects everyday life, health and development. The habilitation team offers support and treatment within the medical, educational, psychological, social and technical fields. Help includes assessment, treatment, the provision of aids, information on the specific disability, and counselling. It also includes information about support offered by the local authority as well as advice on the way accommodation and other environments can be adapted to the child’s needs. Parents and siblings can also receive support. The family may also require help in coordinating different forms of help.

It is important to stimulate speech development from a young age by means including augmentative and alternative communication (AAC), so that the child develops communication skills. If the child also has impaired hearing, parallel measures should be taken to provide auditory training, support, and the appropriate technical aids.

All habilitation varies over time and should be planned and carried out in collaboration between the child, the parents and other individuals that meet the child on a daily basis, for example at the pre-school or school.

The child’s intellectual development determines which form of schooling is most appropriate. For individuals who need support from specialist teachers, special schools can be a good alternative. The individual needs of the child also determine the choice of pre-school, and after-school care.

Young people with visible disfigurements should be offered age-appropriate psychological support to cope with living with an appearance which differs from the norm.

Even small children need their questions answered.

Adults with the syndrome may need continued support and habilitation.

Practical advice


National and regional resources in Sweden

The Swedish Centre for Children and Young People with Syndromes and Congenital Conditions, Uppsala University Children’s Hospital, SE-751 85 Uppsala, Sweden. Tel: +46 18 611 30 40.

Resource personnel

Professor Göran Annerén, Clinical Genetics, Uppsala University Children’s Hospital, SE-751 85 Uppsala, Sweden. Tel: +46 18 611 59 42, email: goran.anneren@igp.uu.se

Associate Professor Mårten Kyllerman, The Queen Silvia Children’s Hospital, SE-416 85 Gothenburg, Sweden. Tel: +46 31 343 47 25.

Courses, exchanges of experience, recreation


Organizations for the disabled/patient associations etc.

FUB, The Swedish National Association for Children, Young People and Adults with Intellectual Disabilities, Industrivägen 7 (visitors address), Box 1181, SE-171 23 Solna, Sweden. Tel: +46 8 508 866 00, fax: +46 8 508 866 66, email: fub@fub.se, www.fub.se.

HRF, The Swedish Association of the Hard of Hearing, Gävlegatan 16, Box 6605, SE-113 84 Stockholm, Sweden. Tel: +46 8 457 55 00, text telephone: +46 8 457 55 01, fax: +46 8 457 55 03, email: hrf@hrf.se, www.hrf.se.

Courses, exchanges of experience for personnel


Research and development



Annerén G, Arvidsson B, Gustavson K-H, Jorulf H, Carlsson G. Oro-facio-digital syndromes I and II: radiological methods for diagnosis and the clinical variations. Clin Genet 1984; 26: 178-186.

Annerén G, Gustavson K-H, Jozwiak S, Kjartansson S, Stromberg B. Abnormalities of the cerebellum in oro-facio-digital syndrome II (Mohr syndrome). Clin Genet 1990; 38: 69-73.

Balci S, Guler G, Kale G, Soylemezoglu F, Besim A. Mohr syndrome in two sisters: prenatal diagnosis in a 22-week-old fetus with post-mortem findings in both. Prenat Diag 1999; 19: 827-831.

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: 1354-1361.

Feather SA, Woolf AS, Donnai D, Malcolm S, Winter RM. The oral-facial-digital syndrome type 1 (OFD1), a cause of polycystic kidney disease and associated malformations, maps to Xp22.2-Xp22.3. Hum Mol Genet 1997; 6: 1163-1167.

Ferrante MI, Giorgio G, Feather SA, Bulfone A, Wright V, Ghiani M et al. Identification of the gene for oral-facial-digital type I syndrome. Am J Hum Genet 2001; 68: 569-576.

Gedeon AK, Oley C, Nelson J, Turner G, Mulley JC. Gene localization for oral-facial-digital syndrome type 1 (OFD1: MIM 31120) proximal to DXS85. Am J Med Genet 1999; 82: 352-354.

Gorlin RJ, Psaume J. Orodigitofacial dysostosis-a new syndrome. J Pediat 1962; 61: 520-530.

Mohr OL. A hereditary lethal syndrome in man. Avh. Norske Videnskad, Oslo 1941; 14: 1-18.

Munke M, McDonald DM, Cronister A, Stewart JM, Gorlin RJ, Zackai EH. Oral-facial-digital syndrome type VI (Varadi syndrome): further clinical delineation. Am J Med Genet 1990; 35: 360-369.

Naiboglu B, Oysu C, Gokceer T. Orofaciodigital syndrome. Ear Nose Throat J 2012; 91: E8-9.

Nevin, NC, Silvestri J, Kernohan DC, Hutchinson WM. Oral-facial-digital syndrome with retinal abnormalities: OFDS type IX. A further case report. Am J Med Genet 1994; 51: 228-231.

Reardon W, Harbord MG, Hall-Craggs MA, Kendall B, Brett EM, Baraitser M. Central nervous system malformations in Mohr’s syndrome. J Med Genet 1989; 26: 659-663.

Rimoin DL, Edgerton MT. Genetic and clinical heterogeneity in the oral-facial-digital syndromes. J Pediatr 1967; 71: 94-102.

Smith RA, Gardner-Medwin D. Orofaciodigital syndrome type III in two sibs. J Med Genet 1993; 30: 870-872.

Thauvin-Robinet C, Cossee M, Cormier-Daire V, Van Maldergem L, Toutain A, Alembik Y et al. 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.

Thauvin-Robinet C, Rousseau T, Durand C, Laurent N, Maingueneau C, Faivre L et al. Familial orofaciodigital syndrome type I revealed by ultrasound prenatal diagnosis of porencephaly. Prenat Diagn 2001; 21: 466-470.

Database references

OMIM (Online Mendelian Inheritance in Man)
Search: mohr syndrome, orofaciodigital syndrome I, orofaciodigital syndrome II

GeneReviews (University of Washington)
www.genetests.org (select “GeneReviews”, then “Titles”)
Search: oral-facial-digital syndrome type 1

Document information

The Swedish Information Centre for Rare Diseases produced and edited this information material.

The medical expert who wrote the draft of this information material is Associate Professor Mårten Kyllerman, The Queen Silvia Children’s Hospital, Gothenburg, Sweden.

Professor Karl-Henrik Gustavson, Uppsala University Hospital, Sweden, revised this material.

The relevant organisations for the disabled/patient associations have been given the opportunity to comment on the content of the text.

An expert group on rare diseases, affiliated with the University of Gothenburg, approved the material prior to publication.

Publication date: 2012-11-30
Version: 3.0
Publication date of the Swedish version: 2012-09-10

For enquiries contact The Swedish Information Centre for Rare Diseases, The Sahlgrenska Academy at the University of Gothenburg, Box 422, SE-405 30 Gothenburg, Sweden. Tel: +46 31 786 55 90, email: ovanligadiagnoser@gu.se.


About the database

This knowledge database provides information on rare diseases and conditions. The information is not intended to be a substitute for professional medical care, nor is it intended to be used as a basis for diagnosis or treatment.