About craniofrontonasal dysplasia

What is craniofrontonasal dysplasia?

Craniofrontonasal dysplasia is a very rare inherited disorder characterized by abnormalities of the head and face (craniofacial area), hands and feet, and certain skeletal bones. 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). Craniofrontonasal dysplasia follows X-linked inheritance in most families, but females are more severely affected than males. An autosomal dominant form of the disorder has also been discussed in the medical literature.

What are the symptoms for craniofrontonasal dysplasia?

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.

What are the causes for craniofrontonasal dysplasia?

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.

What are the treatments for craniofrontonasal dysplasia?

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.

What are the risk factors for craniofrontonasal dysplasia?

Craniofrontonasal dysplasia is a rare genetic disorder that affects the development of the skull, face, and nasal passages. It can also cause other problems like hearing loss.

The exact cause of craniofrontonasal dysplasia is unknown, but it's believed to be due to a combination of genes that may be inherited from your parents.

There are several risk factors for craniofrontonasal dysplasia:

1. Having a family history of the condition. Some people with craniofrontonasal dysplasia have a family history of this disorder, so if you have a child with this condition, you should take them to see your doctor immediately for an evaluation. They'll need to get regular checkups throughout their childhood to make sure they're developing normally and will need treatment for any specific health conditions they develop as they grow older.

2. Being born with multiple congenital defects or syndromes that are associated with Crouzon syndrome (such as Apert syndrome)

3. Having premature birth or low birth weight

4. Having an early diagnosis of Crouzon syndrome

5. Maternal age of 35 years or over at the time of conception (the older the mother, the greater her chances of having a child with craniofrontonasal dysplasia)

6. Mother's family history of craniofrontonasal dysplasia or other genetic conditions

7. Father's family history of craniofrontonasal dysplasia or other genetic conditions

Small head size,Flat nasal bridge,Low, sloping forehead,Eyes that are widely spaced apart and bulging (exophthalmos),Narrow cheeks and small jaw,A prominent, narrow chin
Low muscle tone (hypotonia),Speech delays or problems learning to speak (dysphasia),Hearing loss,Development delays or intellectual disabilities
Arcoxia (etoricoxib),Celebrex (celecoxib),Vioxx (rofecoxib)

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