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 [1] 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 [2]. 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 [2]. Moreover, there is a duplication of the first metatarsal, cuneiform, and cuboid bones [3]. Other skeletal features may include pectus excavatum and scoliosis.

Patients with Mohr syndrome also exhibit systemic manifestations such as conductive deafness [3] [4] and possible developmental complications including laryngeal hypoplasia and tracheal stenosis [5]. Additionally, affected individuals are at risk for cardiac malformations such as endocardial cushion and atrioventricular canal [6] [7]. There are also case reports describing cerebellar atrophy and other changes in patients with this form of OFDS [8].

Intelligence is typically normal in patients with Mohr syndrome.

Physical exam

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.

• 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]

• 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]

• Anemia

  Tests can help rule out physical causes, such as an infection, hormonal problems, anemia, liver problems, or kidney problems. The physician may order a sleep study to rule out a sleeping disorder. [medicalnewstoday.com]

  […] syndrome Connexin 26, Connexin 30, GJB2 gene, GJB6 Cornelia de Lang Syndrome Cru du chat syndrome Crouzon's Syndrome Cytomegalic inclusion disease Duane's Syndrome Ectodermal dysplasia Enlarged Vestibular Aquaduct Syndrome Epstein Syndrome Fanconi's Anemia [californiaearinstitute.com]

  A CELLULE FALCIFORMI (RDG010) ANEMIE EREDITARIE (RDG010) ANEMIE SIDEROBLASTICHE (RDG010) BLACKFAN-DIAMOND, ANEMIA DI (RDG010) FANCONI, ANEMIA DI (RDG010) FAVISMO (RDG010) METAEMOGLOBINEMIA DA DEFICIT DI METAEMOGLOBINAREDUTTASI (RDG010) SFEROCITOSI EREDITARIA [malattierare.toscana.it]

  Smadja N, Krulik M, de Gramont A, Gonzalez-Canali G, Audebert AA, Debray J: Refractory anemia with excess of blast in transformation. Clinical, hematologic, and cytogenetic findings in nine patients. Cancer Genet Cytogenet 42:55–65 (1989). [karger.com]

• Fever

  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]

• Multiple Congenital Anomalies

  congenital anomaly syndrome ( Smith-Lemli-Opitz syndrome type 2) orofaciodigital syndromes Varadi-Papp syndrome (OFDS6) syndromal preaxial poydactyly Mohr syndrome Majewski type of short rib Towne syndrome Varadi-Papp syndrome acrocephalopolydactyly [humpath.com]

• Tachypnea

  Child also had some unusual features like the presence of systolic murmur, suggestive of congenital heart disease, tachypnea [2] 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]

• Midline Cleft of Tongue

  Very rare familial association of deafness with minor facial hypoplasia and minor midline cleft (tongue, lip, palate). [accessanesthesiology.mhmedical.com]

• Pachyonychia

  Optic atrophy Digitised copy available UGC155/3/3/71 OI, Osteogenesis imperfecta Digitised copy available UGC155/3/3/72 OP, Oculo-pharyngeal myopathy Digitised copy available UGC155/3/3/73 OT, Otosclerosis Digitised copy available UGC155/3/3/74 PA, Pachyonychia [wellcomelibrary.org]

• Hyperkeratosis

  Histologic examination postaxial or preaxial nubbin tissue resembles the histology of a congenital traumatic neuroma and demonstrates hyperkeratosis and acanthosis overlying many nerve bundles in the dermis. [clinicaladvisor.com]

• Angioedema

  EREDITARIO (RC0191) ANGIOEDEMA ACQUISITO DA DEFICIT DI C1 INIBITORE (RC0200) CARENZA CONGENITA DI ALFA-1-ANTITRIPSINA (RC0210) BEHÇET, MALATTIA DI (RC0220) SINDROME DA ANTICORPI ANTIFOSFOLIPIDI (FORMA PRIMITIVA) (RC0230) CALCINOSI TUMORALE (RC0241) FEBBRE [malattierare.toscana.it]

• Dermatitis

  Digitised copy available UGC155/3/3/22 CT, Catalase UGC155/3/3/23 Cardiomyopathy Digitised copy available UGC155/3/3/24 DA, Diaphysial aclasis (or multiple exostosis) UGC155/3/3/25 DE, Deafness UGC155/3/3/26 DG, Dermatoglyphic syndromes UGC155/3/3/27 DH, Dermatitis [wellcomelibrary.org]

• Koilonychia

  […] disease Digitised copy available UGC155/3/3/50 ICB, Bullous ichthyosiform erythroderma UGC155/3/3/51 II, unidentified disease UGC155/3/3/52 INH, unidentified disease UGC155/3/3/53 KA, Kartagener's Syndrome Digitised copy available UGC155/3/3/54 KN, Koilonychia [wellcomelibrary.org]

• Ectopia Lentis

  lentis Digitised copy available UGC155/3/3/57 LI, Lipoma draft pedigree chart UGC155/3/3/58 LS, Laustia pedigrees UGC155/3/3/59 MA, Marfan's Syndrome Digitised copy available UGC155/3/3/60 MD, Muscular dystrophy UGC155/3/3/61 MI, Milroy's Disease Digitised [wellcomelibrary.org]

• Short Hands

  hands with clinodactyly of fifth finger, syndactly, post axial polydactyly of hands, preaxial polysyndactyly of feet and duplication of thumb and hallux)[2]. [journalofpediatriccriticalcare.com]

• Pierre Robin Syndrome

  OAV Spectrum Paget's Disease Pendred syndrome Pierre Robin Syndrome Pyle's Disease Refsum's disease Ring 6 Disorder Saddle-Nose syndrome Schiebe aplasia Surcardiac syndrome Tay Sach's Disease Townes-Brock Syndrome Treacher Collins Syndrome Trisomy 13 [californiaearinstitute.com]

  ICD-10-CM Diagnosis Code G83.9 Paralytic syndrome, unspecified 2016 2017 2018 2019 Billable/Specific Code oculofacial, congenital Q87.0 (Moebius) Pierre Robin deformity or syndrome Q87.0 Robin Q87.0 (-Pierre) Syndrome - see also Disease congenital facial [icd10data.com]

• Phenylketonuria

  […] available UGC155/3/3/72 OP, Oculo-pharyngeal myopathy Digitised copy available UGC155/3/3/73 OT, Otosclerosis Digitised copy available UGC155/3/3/74 PA, Pachyonychia UGC155/3/3/75 PD, Polydactyly UGC155/3/3/76 PE, Pelger-Huet Anomaly UGC155/3/3/77 PK(U), Phenylketonuria [wellcomelibrary.org]

• Nystagmus

  […] available UGC155/3/3/66 Papers on acoustic neuromania Digitised copy available UGC155/3/3/67 NP, Nail-Patella Syndrome (Hereditary osteo-onycho-dystrophy/dysplasia) UGC155/3/3/68 NV, Nevoid basal cell carcinoma Digitised copy available UGC155/3/3/69 NY, Nystagmus [wellcomelibrary.org]

  Vestibular function evaluation included vestibular-evoked myogenic potentials (ocular VEMP, oVEMP and cervical VEMP, cVEMP), oculomotor function tests, positional nystagmus tests, positioning nystagmus tests and bithermal caloric tests. [bmcmedgenet.biomedcentral.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.

Imaging

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 [9]. Moreover, other recommended studies include magnetic resonance imaging (MRI) of the brain, audiometric assessment, an ophthalmologic evaluation, and abdominal ultrasound [3]. OFDS patients with heart murmurs warrant cardiac evaluation with echocardiography [9]. Laryngoscopy may be indicated as well [9]. Since Mohr syndrome also affects dentition, a panoramic x-ray is required [10].

Prenatal

Routine widespread use of prenatal ultrasonography allows for the detection of fetal defects, which consequentially leads to genetic counseling [11] and the appropriate assessment.

There are two main types of clinical studies: Clinical trials determine if a new test or treatment for a disease is effective and safe by comparing groups receiving different tests/treatments. [rarediseases.info.nih.gov]

[…] 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]

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]

[edit] 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.[1] History[edit] This condition was first described in 1960.[7] Epidemiology[edit] 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. [3] NOTCH3 codes for a transmembrane receptor protein whose function is not precisely known. [emedicine.medscape.com]

Proximal hamstring tendinopathy: pathophysiology, diagnosis and treatment. Br J Hosp Med. 2018;79(7):389–94. https://doi.org/10.12968/hmed.2018.79.7.389 Beatty NR, Felix I, Hettler J, Moley PJ, Wyss JF. [ouci.dntb.gov.ua]

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]

1. Jones KL, Jones MC, Del Campo M. Smith’s recognizable patterns of human malformation. 5th ed. Philadelphia, PA: Saunders Elsevier; 1997. P. 264.
2. Havle A, Shedge S, Malashetti S, Jain V. Oro-facial-digital syndrome type II with otolaryngological manifestations. J Oral Maxillofac Pathol. 2015;19(2):266.
3. Gurrieri F, Franco B, Toriello H, Neri G. Oral-facial-digital syndromes: review and diagnostic guidelines. Am J Med Genet A. 2007;143A(24):3314-23.
4. Prpic I, Cekada S, Franulovic J. Mohr syndrome (oro-facial-digital syndrome II) – A familial case with different phenotypic findings. Clin Genet. 1995;48(6):304–7.
5. Steichen-Gersdorf E, Gassner I, Covi B, Fischer H. Oral-facial-digital syndrome II. Transitional type between Mohr and Majewski syndrome: Report of a new case with congenital stenosis of the trachea. Clin Dysmorphol. 1994;3(3):245–50.
6. Digilio MC, Marino B, Giannotti A, Dallapiccola B. Orocardiodigital syndrome: An oral–facial–digital type II variantassociated withatrioventricular canal. 1996;33(5):416-8.
7. Hsieh Y, Hou J. Oral–facial–digital syndrome with Y-shaped fourth metacarpals and endocardial cushion defect. 1999; 86(3):278-81.
8. Annerén G, Gustavson KH, Jòzwiak S, Kjartansson S, Strömberg B. Abnormalities of the cerebellum in oro-facio-digital syndrome II (Mohr syndrome). Clin Genet. 1990; 38(1):69-73.
9. 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.
10. Lage C, Pinto da Silva L, Fonseca L, Cruz R. Diagnostic and clinical procedures of a patient with oral-facial-digital type II syndrome: a case report. J Clin Exp Dent. 2011;3(3):e261-4.
11. Iaccarino M, Lonardo F, Giugliano M, Bruna D. Prenatal diagnosis of Mohr syndrome by ultrasonography. Prenat Diagn. 1985;5(6):415-8.