Mohr syndrome, one of the numerous forms of oro-facial-digital syndrome (OFDS), is a rare autosomal recessive disorder characterized by specific anomalies of the oral cavity, face, and digits. The diagnosis is clinical and hence a thorough physical exam is essential.
Mohr syndrome is the second of at least nine distinct subtypes of oro-facial-digital syndrome (OFDS). Also referred to as type II OFDS, Mohr syndrome is a rare autosomal recessive disorder  which is characterized by a cluster of congenital anomalies. It features oral deformities such as a cleft or high-arched palate, cleft lip, tongue nodules, and absent teeth. Additionally, Mohr syndrome is marked by dysmorphic faces such as a broad nose accompanied by a bifid tip . Furthermore, the digital abnormalities include pre- and post-axial polydactyly of the hands and feet, partial bilateral duplication of the hallux, syndactyly, clinodactyly, polydactyly, and brachydactyly . Moreover, there is a duplication of the first metatarsal, cuneiform, and cuboid bones . Other skeletal features may include pectus excavatum and scoliosis.
Patients with Mohr syndrome also exhibit systemic manifestations such as conductive deafness   and possible developmental complications including laryngeal hypoplasia and tracheal stenosis . Additionally, affected individuals are at risk for cardiac malformations such as endocardial cushion and atrioventricular canal  . There are also case reports describing cerebellar atrophy and other changes in patients with this form of OFDS .
Intelligence is typically normal in patients with Mohr syndrome.
It is important to conduct a thorough exam and to note the specific physical findings described above. Diagnosing Mohr syndrome and differentiating it from the other variants of OFDS is challenging since many share overlapping features.
Entire Body System
- Short Stature
Conductive hearing loss (anomaly of unci); mild hypoplasia of zygomatic arch, maxilla and body of mandible; flat nasal bridge; partial cleft of lip or palate, hyperplastic frenulum; midline cleft of tongue and/or nodules on the tongue; short stature, [accessanesthesiology.mhmedical.com]
[…] tibia) and pre and or postaxial polydactyly (primary manifestations) Other findings include pectus excavatum and short stature OFD V (Thurston syndrome) Autosomal recessive includes polydactyly and median cleft lip only Only one affected individual has [en.wikibooks.org]
OFD4: Autosomal recessive has tibial involvement, polydactyly, pectus excavatum and short stature. OFD5: Autosomal recessive includes polydactyly and median cleft lip only. [japi.org]
stature • Inheritance: autosomal recessive Oral-facial-digital syndrome X (aka, Figuera syndrome) (Figuera et al 1993) • Distinguishing feature: fibular aplasia • Inheritance: autosomal recessive Oral-facial-digital syndrome XI (aka, Gabrielli syndrome [medlink.com]
- Pallister-Hall Syndrome
[…] palate association) Pallister-Hall syndrome Rutledge lethal multiple congenital anomaly syndrome ( Smith-Lemli-Opitz syndrome type 2) orofaciodigital syndromes Varadi-Papp syndrome (OFDS6) syndromal preaxial poydactyly Mohr syndrome Majewski type of [humpath.com]
[…] lip/palate syndrome Ellis van Creveld syndrome McKusick-Kaufman syndrome Mirror hand deformity (ulnar dimelia)  Mohr syndrome Oral-facial-digital syndrome Pallister-Hall syndrome Rubinstein-Taybi syndrome Short rib polydactyly VATER association [emedicine.medscape.com]
Pallister-Hall syndrome, Rubinstein-Taybi syndrome, Smith-Lemli-Opitz syndrome, short rib polydactyly, trisomy 13 and 21, tibial hemimelia, VATER association (Vertebral [defects], [imperforate] Anus, Tracheoesophageal [fistula], Radial and renal [dysplasia [clinicaladvisor.com]
There is some phenotypic overlap with Pallister-Hall Syndrome (PHS), but the gene for PHS can be tested for so that this diagnosis can be ruled out or confirmed. Inheritance is autosomal recessive. OFD VII is also called Whelan Syndrome. [genome.gov]
In particular, some patients with Beemer-Langer syndrome, Pallister-Hall syndrome, and Majewski short-rib polydactyly syndrome have phenotypic features indistinguishable from variants of oral-facial-digital syndrome. [medlink.com]
- Developmental Disorder
Oral-facial-digital syndromes (OFDS) are a group of rare genetic developmental disorder that affects the mouth, face, digits and also may cause some problems on the central nervous, kidney and the other organs. [radiopaedia.org]
Introduction Oro-facial-digital syndromes are a heterogeneous group of developmental disorders in which at least nine different forms have been described. [japi.org]
Orofacial digital syndrome (OFDS) is a rare congenital disorder characterized by a range of clinical anomalies, such as malformations of the oral cavity including mouth, tongue, and teeth as well as developmental disorder of the face, head, nose, eyes [bmcmusculoskeletdisord.biomedcentral.com]
- Recurrent Infection
If the CGS includes the Bruton agammaglobulinemia tyrosine kinase ( BTK ) gene, recurrent infections secondary to this X-linked agammaglobulinemia (XLA; see this term) are present. [rarediseases.info.nih.gov]
If the CGS includes the Bruton agammaglobulinemia tyrosine kinase (BTK) gene, recurrent infections secondary to this X-linked agammaglobulinemia (XLA) are present. [findzebra.com]
At age 2 years, bilateral hearing loss appeared and recurrent infections led to a diagnosis of Bruton agammaglobulinemia. At age 15, a progressive visual loss was noticed. [n.neurology.org]
infections due to XLA in a male patient should elicit sequencing of the TIMM8A gene. [en.wikipedia.org]
Frequent fever, tachypnea and recurrent respiratory infections were observed in later days. The child had many typical and common features of Mohr syndrome along with few uncommonly reported features. [ijcasereportsandimages.com]
Child also had some unusual features like the presence of systolic murmur, suggestive of congenital heart disease, tachypnea  and recurrent respiratory infections. [ijcasereportsandimages.com]
[…] oral-facial-digital II: report of two cases. ( 4527225 ) Goldstein E....Medina J.L. 1974 19 Mohr syndrome with subclinical expression of the bifid great toe. ( 4414705 ) Levy E.P....Fraser F.C. 1974 20 Syndrome characterized by lingual malformation, polydactyly, tachypnea [malacards.org]
0002132 Protruding ear Prominent ear Prominent ears [ more ] 0000411 Scoliosis Abnormal curving of the spine 0002650 Shortening of the tibia Shortening of the shankbone Shortening of the shinbone [ more ] 0006436 Syndactyly Webbed fingers or toes 0001159 Tachypnea [rarediseases.info.nih.gov]
Jaw & Teeth
- High Arched Palate
High-arch palate which is associated with some congenital syndromes, is a known cause of difficult laryngoscopy. [bmcmusculoskeletdisord.biomedcentral.com]
high arch palate,lobulated tongue,syndactly,polydactyl and duplication of first toe. [apicareonline.com]
The second case was a 4-year-old male who had dysmorphic features; Antimongoloid eye slant, prominent ears, broad nose bridge, high arched palate, cleft soft palate, lingual nodule, preaxial and posaxial polydactyly with syndactyly in both hands, bilateral [aclr.com.es]
It features oral deformities such as a cleft or high-arched palate, cleft lip, tongue nodules, and absent teeth. Additionally, Mohr syndrome is marked by dysmorphic faces such as a broad nose accompanied by a bifid tip. [symptoma.com]
The facial and oral features include tongue nodules, cleft or high-arched palate, missing teeth, broad nose; cleft lip. The digital features include clinodactyly, polydactyly, syndactyly, brachydactyly and duplication of the hallux. [jomfp.in]
- Midline Cleft of Tongue
Very rare familial association of deafness with minor facial hypoplasia and minor midline cleft (tongue, lip, palate). [accessanesthesiology.mhmedical.com]
- Low Set Ears
The extra-oral examination revealed frontal bossing, down-sloping forehead, broad nasal base, uneven nostrils, wide set eyes, low-set ears, flat midface, dry skin and coarse hair. [jofs.in]
Facial anomalies in OFDS type IV have included broad nasal root and tip, hypertelorism or telecanthus, micrognathia, hypoplastic mandible, and low-set ears. [hindawi.com]
There were some unusual findings in the facies like presence of epicanthic folds and low set ears (figure 1). [ijcasereportsandimages.com]
set ears [Figure 3] and tongue nodules [Figure 4]. [jomfp.in]
She presented with typical features of OFDS type II (Fig. 1), which included mouth cavity and facial deformities, tongue nodules, missing central incisors, high arch palate, broad nose, midline lip cleft, hypertelorism, as well as low-set ears (Fig. 2 [bmcmusculoskeletdisord.biomedcentral.com]
- Ear Fullness
Fig. 1 Orofacial manifestations of Mohr syndrome including the patient’s face (a), midline lip cleft (b), high-arch palate (b), absence of central incisors (b) and presence of tongue nodule (c) Full size image Fig. 2 Low-set ear Full size image Fig. 3 [bmcmusculoskeletdisord.biomedcentral.com]
- Foot Deformity
Mirror foot deformity of right foot was corrected through a 94-min surgery. During the operation, the surgeon excised pre and postaxial rays in order to create a suitable foot for wearing shoes. [bmcmusculoskeletdisord.biomedcentral.com]
The lobulated tongue with hypertrophied frenula, median pseudocleft of the upper lip, and hearing loss are findings characteristic of OFDS type II whereas the tibial dysplasia and club foot deformities are characteristic of OFDS type IV. [hindawi.com]
- Short Hands
hands with clinodactyly of fifth finger, syndactly, post axial polydactyly of hands, preaxial polysyndactyly of feet and duplication of thumb and hallux). [journalofpediatriccriticalcare.com]
Face, Head & Neck
The 1st was a 13-week-old fetus with hypertelorism; a median cleft defect of the upper lip, soft palate, and uvula; a polypoid lower lip and multiple frenula of the tongue adherent to the mandible; a congenital heart defect; pre- and postaxial polydactyly [insights.ovid.com]
The Mohr syndrome (oral-facial-digital II [OFD II]) is characterized by a lobate tongue, midline cleft of the lip, high arched or cleft palate, broad nasal root with wide bifid nasal tip, hypertelorism, micrognathia, brachydactyly, syndactyly and polydactyly [jamanetwork.com]
Abstract We present a male infant with hypertelorism, median pseudo-cleft of the upper lip and cleft palate, lobulated tongue, hypoplastic larynx and epiglottis, mesomelic shortening of limbs with particularly short and broad tibiae, polydactyly of the [jmg.bmj.com]
Major changes include hypertrophic frenula, dental anomalies, lingual hamartomas, cleft lip or palate, ocular hypertelorism, brachydactyly, polydactyly, and syndactyly. [medlink.com]
Acetazolamide for the treatment of migraine with aura in CADASIL. Neurology. 2001 Dec 11. 57(11):2144-5. [Medline]. Weller M, Dichgans J, Klockgether T. Acetazolamide-responsive migraine in CADASIL. Neurology. 1998 May. 50(5):1505. [Medline]. [emedicine.medscape.com]
Every newborn must be examined completely from head-to-toe, which is a key component of the neonatal assessment, The presence of any anomaly should prompt the clinician to look for other abnormalities. Patients presenting with oral, facial and digital malformations should raise suspicion for OFDS, which is a clinical diagnosis. Hence the workup consists of the patient and family history and a detailed physical exam. Furthermore, investigation of other possible manifestations may be undertaken in order to ascertain the full clinical picture.
Patients with OFDS are evaluated with a skeletal survey to determine which digits and bones are involved and to add clarity regarding the present deformities . Moreover, other recommended studies include magnetic resonance imaging (MRI) of the brain, audiometric assessment, an ophthalmologic evaluation, and abdominal ultrasound . OFDS patients with heart murmurs warrant cardiac evaluation with echocardiography . Laryngoscopy may be indicated as well . Since Mohr syndrome also affects dentition, a panoramic x-ray is required .
Routine widespread use of prenatal ultrasonography allows for the detection of fetal defects, which consequentially leads to genetic counseling  and the appropriate assessment.
[…] in Adults (Adult Treatment Panel III). [cigota.rs]
Management and treatment Treatment of MTS is symptomatic and evolves over time. Hearing aids are used with variable success. [findzebra.com]
Other advanced orthopedic treatments offered at our centers include personalized knee replacements, ultrasound-guided corticosteroid and hyaluronan injections, concussion management, bone marrow aspirate concentrate (BMAC) treatments and minimally invasive [advancedosm.com]
 Symptomatic Treatment The treatment for Mohr-Tranebjærg vary depending on the symptoms and the evolution of these symptoms over time. Since hearing loss is prevalent in those with Mohr-Tranebjærg, hearing aids, devices, or cochlear implants [en.wikipedia.org]
Prognosis Prognosis is poor. The combination of deafness and blindness severely affects communication, while the ongoing movement disorder results in an increasingly unstable gait. [rarediseases.info.nih.gov]
 Prognosis is poor. [en.wikipedia.org]
Prenatal ultrasound examination was very useful in the management, prognosis and detection of this case. The prenatal diagnosis is necessary for the detection of fetal abnormalities to all pregnancies and especially for the risk categories. 1. [medresearch.in]
Long-term prognosis and causes of death in CADASIL: a retrospective study in 411 patients. Brain. 2004 Nov. 127:2533-9. [Medline]. Ruchoux MM, Maurage CA. [emedicine.medscape.com]
Elsevier Health Sciences, 18.08.2013 - 979 Seiten Smith’s Recognizable Patterns of Human Malformation has long been known as the source to consult on multiple malformation syndromes of environmental and genetic etiology as well as recognizable disorders [books.google.de]
Elsevier Health Sciences, ١٨/٠٨/٢٠١٣ - 979 من الصفحات Smith’s Recognizable Patterns of Human Malformation has long been known as the source to consult on multiple malformation syndromes of environmental and genetic etiology as well as recognizable disorders [books.google.com]
They are organised into groups, and further divided into clinical, etiological or histopathological sub-types. [orpha.net]
[…] polydactyly preaxial polydactylytype 2: polydactyly of a triphalangeal thumb preaxial polydactylytype 3: polydactyly of an index finger preaxial polydactyly type 4: polysyndactyly central polydactyly (medial ray) postaxial polydactyly (lateral ray) Etiology [humpath.com]
Etiology MTS is caused by either a mutation in the TIMM8A gene (located to Xq22) or by a CGS at Xq22, resulting in a deafness-dystonia peptide 1 (DDP1) deficiency. [rarediseases.info.nih.gov]
The discussion covers the phenotype spectrum, epidemiology, mode of inheritance, pathogenesis, and clinical profile of each condition, all of which is accompanied by a wealth of illustrations. [books.google.com]
Epidemiology Prevalence is unknown. More than 90 cases (37 families) are known, but not all cases have been reported in the literature. [rarediseases.info.nih.gov]
Epidemiology Mohr-Tranebjaerg syndrome (MTS) prevalence is unknown. More than 90 cases (37 families) are known, but not all cases have been reported in the literature. [findzebra.com]
Life expectancy is highly variable and can range from death in the teenage years (after a rapidly progressive dystonia) to those that live into their 60's. History This condition was first described in 1960. Epidemiology Mohr-Tranebjᴂrg [en.wikipedia.org]
Congenital limb deficiency in Japan: a cross-sectional nationwide survey on its epidemiology. BMC Musculoskelet Disord. 2018;19(1):262. [bmcmusculoskeletdisord.biomedcentral.com]
Pathophysiology CADASIL is caused by a mutation in the NOTCH3 gene on chromosome 19q12. The gene mutation was first identified in 1996.  NOTCH3 codes for a transmembrane receptor protein whose function is not precisely known. [emedicine.medscape.com]
Specific inhibitors and promoters of calcium action in the excitation-contraction coupling of heart muscle and their role in the prevention or production of myocardial lesions. In Calcium and the Heart, ed. [books.google.es]
In those with secondary complications, intravenous immunoglobulin may prevent infections in XLA. Furthermore, live viral vaccines should be avoided in cases of XLA. [rarediseases.info.nih.gov]
Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs [emedicine.medscape.com]
CASE REPORT Year : 2006 | Volume : 24 | Issue : 5 | Page : 41-43 Dens evaginatus of anterior teeth (talon cusp) associated with other odontogenic anomalies Department of Pedodontics and Preventive Dentistry, Govt. [jisppd.com]
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- Digilio MC, Marino B, Giannotti A, Dallapiccola B. Orocardiodigital syndrome: An oral–facial–digital type II variantassociated withatrioventricular canal. 1996;33(5):416-8.
- Hsieh Y, Hou J. Oral–facial–digital syndrome with Y-shaped fourth metacarpals and endocardial cushion defect. 1999; 86(3):278-81.
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- Shawky RM, Elsayed SM, Abd-Elkhalek HS, Gad S. Oral-facial-digital syndrome type II: Transitional type between Mohr and Varadi. Egyptian J Med Human Genet, 2013; 14(3): 311–5.
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