Última actualización:
August 11, 2016
Años publicados: 1996, 2003, 2016
NORD gratefully acknowledges Prof. Dr. Peter Wieacker, Director of the Institute of Human Genetics, University Hospital Muenster, Germany,for assistance in the preparation of this report.
Craniofrontonasal dysplasia (CFND) is a very rare inherited disorder characterized by body – especially facial – asymmetry, midline defects, skeletal abnormalities, and dermatological abnormalities. Major symptoms of this disorder may include widely spaced eyes (ocular hypertelorism), a groove (cleft) on the tip of the nose, an unusually wide mouth, malformations of the fingers and toes, and/or underdevelopment of portions of the face (midface hypoplasia), such as the forehead, nose, and chin. In addition, the head may have an unusual shape due to premature closure of the fibrous joints (sutures) between certain bones in the skull (coronal synostosis). CFND is an X-linked genetic disorder that occurs mostly in females and is caused by a mutation in the EFNB1 gene.
The symptoms of CFND vary greatly in number and severity among affected individuals. The most common symptoms of this disorder include widely spaced eyes (ocular hypertelorism), a vertical groove (cleft) on the tip of the nose, shoulder and limb abnormalities and/or underdevelopment of the middle portion of the face (e.g., forehead, nose, and/or chin). The head typically has an unusual shape due to premature closure of the fibrous joints (sutures) between certain bones in the skull (coronal synostosis) resulting in facial asymmetry.
Some affected individuals may have additional abnormalities of the head and facial (craniofacial) area. These may include a broad nose and face; a broad and high forehead; cleft lip and palate; low-set ears and a webbed neck. Females usually have thick, wiry and curly hair that appears at 2-3 months of age.
Affected individuals may also have webbing of the fingers and toes (syndactyly); a curved fifth finger (clinodactyly); unusually broad fingers and/or toes, especially the first “big” toe; and/or nails that are grooved, split, concave, and/or brittle.
Other physical characteristics sometimes associated with CFND may include narrow sloping shoulders. Several skeletal abnormalities may be present such as malformation of a long, flat, vertical bone in the center of the chest (sternum); malformation of the collarbone (clavicle); backward curvature of the spine (lordosis); and/or sideways curvature of the spine (scoliosis). One limb may be shorter than the other. Underdevelopment of one breast is sometimes seen in females. In addition, one shoulder may be unusually high due to the failure of the major bone of the shoulder (scapula) to move into the appropriate position during fetal development (Sprengel deformity). (For more information on Sprengel deformity, see the Related Disorders section of this report.) Females may have a uterus anomaly that may cause an increased incidence of miscarriages.
Some individuals affected by CFND may also have diminished muscle tone (hypotonia), developmental delays, hearing impairment (sensorineural deafness), a sunken chest (pectus excavatum), and/or protrusion of part of the stomach and/or small intestines into the chest cavity (diaphragmatic hernia). Several reports have linked CFND to Poland syndrome which is a condition in which there is an absence of chest wall muscles on one side of the body and abnormally short, webbed fingers on the hand on the same side. Some patients have a complete or partial absence of the corpus callosum, the band of nerves that connect the two hemispheres of the brain.
Some affected males may have an abnormal fold of skin extending around the base of the penis (shawl scrotum) and/or improper development of the tube leading from the bladder that discharges urine (urethra). In addition, the urinary opening may be misplaced, such as on the underside of the penis (hypospadias). It is possible that a male may show no symptoms but be a carrier of the gene mutation for CFND.
CFND is an X-linked disorder caused by a mutation in the EFNB1 gene. There have been at least 33 different mutations of the EFNB1 gene identified. All daughters of affected males are affected, consistent with X-linked inheritance.
CFND is a very rare genetic disorder that affects females more often than males. Females have a more severe form of the disorder.
A diagnosis of CFND may be suspected after a thorough clinical evaluation and characteristic physical findings. Molecular genetic testing for mutations in the EFNB1 gene is available to confirm the diagnosis. CFND can sometimes be detected before birth (prenatally) by ultrasound.
Treatment
Treatment of CFND depends upon the specific malformations and their severity in each individual patient, and the timing of diagnosis. Surgery may be performed to correct craniofacial deformities and malformations of the hands and feet. Surgery may also be used to narrow the nose and reduce neck webbing. A team approach for infants and children with this disorder may be of benefit and may include special social support and other medical services. Other treatment is symptomatic and supportive.
Genetic counseling is recommended for affected individuals and their families.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov . All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Reichenberger E and Mulliken JB. Craniofrontonasal Syndrome. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003:183-4.
Cohen MM, MacLean RE, eds. Craniosynostosis: diagnosis, evaluation, and management, 2nd ed. New York: Oxford University Press, 2000:380-384.
Buyse ML, ed. The Birth Defects Encyclopedia. Blackwell Scientific Publications, 1990, 459-460, 1308-09.
JOURNAL ARTICLES
Kawamoto HK, Heller JB, Heller MM, Urrego A, Gabbay JS, Wasson KL, Bradley JP. Craniofrontonasal dysplasia: a surgical treatment algorithm. Plastic and Reconstructive Surgery. 2007; 120:1943-1956.
Wieacker P, Wieland I. Clinical and genetic aspects of craniofrontonasal syndrome: towards resolving a genetic paradox. Molecular Genetics and Metabolism. 2005; 86: 110-116.
Wieland I, Jakubiczka S, Muschke P, Cohen M, Thiele H, Gerlach KL, Adams RH, Wieacker P. Mutations of the ephrin-B1 gene cause craniofrontonasal syndrome. Am J Hum Genet. 2004 Jun;74(6):1209-15.
Saavedra D, Richieri-Costa A, Guion-Almeida ML, et al. Craniofrontonasal syndrome: study of 41 patients. Am J Med Genet 1996:61:147-151.
Grutzner E, et al. Craniofrontonasal dysplasia: phenotypic expression in females and males and genetic considerations. Oral Surg Med Oral Pathol 1988:65(4):436-44.
INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University; Entry No. 304110; Last Update: 02/18/2014. https://omim.org/entry/304110 Accessed July 6, 2016.
Craniofrontonasal dysplasia. Genetic and Rare Diseases Information Center (GARD). Last Update 9/23/2015. https://rarediseases.info.nih.gov/gard/1578/craniofrontonasal-dysplasia/Resources/1 Accessed July 6, 2016.
NORD y la Fundación MedicAlert se han asociado en un nuevo programa para brindar protección a pacientes con enfermedades raras en situaciones de emergencia.
Aprende más https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Asegurarse de que los pacientes y los cuidadores estén equipados con las herramientas que necesitan para vivir su mejor vida mientras manejan su condición rara es una parte vital de la misión de NORD.
Aprende más https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/Este programa de asistencia, primero en su tipo, está diseñado para los cuidadores de un niño o adulto diagnosticado con un trastorno raro.
Aprende más https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
View report