Frontonasal dysplasia (FND) is a congenital midfacial malformation involving the nose, eyes, and forehead [1]. It is believed to be due to the defective migration of the neural crest cells during embryologic midline nasal development although the exact etiology for the malformation is unknown.

It is known to occur sporadically but autosomal dominant, autosomal recessive, and X-linked patterns have also been reported [1] [2]. Recently there have been studies linking FND with autosomal recessive mutations in the homeobox aristaless-like genes ALX1[3], ALX3 [4], ALX4 [5].

The presentation of FND is variable. To be described as FND the condition should include two or more of the following manifestations: hypertelorism, skin covered gap between the forehead bones (anterior cranium bifidum occultum), midline cleft involving the nose, palate and upper lip, broad base of the nose, clefting of the nasal ala, absence of the nasal tip, and widow's peak hairline along the frontal bone [6]. Twice as many males have been reported to have hypertelorism as compared to females [7]. Other abnormalities such as cataracts, colobomas, conductive hearing loss and corpus callosum agenesis can also be present.

Occasionally FND is associated with certain syndromes and other malformations like central nervous system abnormalities [8], tetralogy of Fallot, tibial aplasia, aural and cerebral anomalies. Individuals with FND usually have a normal intelligence quotient (IQ).

Several authors have published classifications of the highly variable midline facial cleft malformations [9] [10] [11]. DeMyer classified midline clefts into those with normal or excessive tissue (median cleft face syndrome) and those with deficient tissue or holoprosencephaly [9]. Sedano termed the median cleft face syndrome as frontonasal dysplasia [10]. Based on the genetic causes and clinical presentation, three types of FND have been described. In FND type 1 patients have nasal anomalies and ptosis. FND type 2 patients have hair loss with agenesis of the parietal bones, while males could have genital anomalies. FND type 3 individuals have ocular anomalies ranging from anophthalmia to microphthalmia, low set ears, and severe facial anomalies.

• Pain

  Stay current with coverage of hot topics including MRSA, neonatal pain, cardiovascular fetal interventions, care of the late preterm infant, and the developing intestinal microbiome. [books.google.com]

  After many painful surgeries as an infant, the 15-year-old Puerto Rican has travelled to Dallas to receive the surgery, in hopes of achieving normalcy. [dailymail.co.uk]

  I still experience pain from 32 years ago. This is going to bother me for the rest of my life." Lee admits he was picked on in school and has now isolated himself. Botched by Nature (Image: E!) "I was teased in school. [mirror.co.uk]

  “She keeps pressing on her nose and saying she hopes she can’t feel the pain, so she’s not scared at all,” said Adan. “She’s brave.” [thestar.com]

• Turkish

  […] ay, Acrocallosal syndrome: report of five Turkish patients, Clinical Dysmorphology, 10.1097/00019605-200410000-00008, 13, 4, (241-246), (2004). [doi.org]

  Language: English | Turkish This article has been cited by other articles in PMC. Abstract Frontonasal dysplasia is a rare congenital anomaly affecting the eyes, nose and forehead, and occurs sporadically in most of the cases. [ncbi.nlm.nih.gov]

• Hearing Impairment

  impairment Conductive deafness Conductive hearing loss [ more ] 0000405 Craniosynostosis 0001363 Cryptorchidism Undescended testes Undescended testis [ more ] 0000028 Flat occiput 0005469 Holoprosencephaly 0001360 Hydrocephalus Too much cerebrospinal [rarediseases.info.nih.gov]

Although FND is typically diagnosed in the neonatal period, there have been reports of fetuses being diagnosed antenatally with the malformation [8] [12]. When noticed at birth, the workup should include a detailed history and physical examination for identification of FND as well as associated respiratory problems, cardiac, neurological, and limb malformations. The presence of at least two or more of the characteristic morphological features of FND helps to clinch the diagnosis. Radiological tests like X-ray of the skull and computed tomography (CT scan) are important for confirming the diagnosis. CT scan is the gold standard for diagnosing FND [13].

Other tests like an electrocardiogram or a two-dimensional echocardiogram may be required to detect associated cardiac abnormalities.

Antenatal ultrasound is useful to detect hypertelorism and cranial malformations like encephalocele [8]. There is a high incidence of a craniofacial malformation in the next sibling, so genetic counseling is important since genetic testing is as yet unavailable [14].

• Polyps

  It is a triad of developmental defects of the face, comprising midline cleft of the upper lip, nasal and facial skin polyps and central nervous system lipomas. [en.wikipedia.org]

A treatment algorithm for craniofrontonasal dysplasia based on timing and technique is offered to decrease the need for revision and improve outcomes. [doi.org]

What are the treatment options? Treatment for FND begins with an accurate diagnosis and thorough evaluation of the patient’s unique expression of the condition. As a result, Dr. [houstoncraniofacial.com]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

In conclusion, the presence of frontonasal dysplasia in a prenatal ultrasonography should always be followed by a fetal MRI with routine screening for periventricular nodular heterotopias so as to establish a more adequate prognosis for the family. [ncbi.nlm.nih.gov]

Treatment and prognosis No specific treatment is available. Surgical intervention is often required for midline facial defects 9. [radiopaedia.org]

Slavotinek, Subtypes of frontonasal dysplasia are useful in determining clinical prognosis, American Journal of Medical Genetics Part A, 143A, 24, (3069-3078), (2007). Anne V. Hing, Nadia Syed and Michael L. [doi.org]

The prognosis depends on the range of the affected area. We have not found any particular syndrome which would include all our ultrasound findings. Our final diagnosis was a severe frontonasal dysplasia associated with cardiopathy. [sonoworld.com]

Our aim was to evaluate FND patients for distinct phenotypes within the FND spectrum and to determine the evidence for a genetic etiology in each of the different subtypes. [ncbi.nlm.nih.gov]

Summary Epidemiology The prevalence is unknown but the condition is rare. Clinical description The clinical picture is highly variable, but the major findings include hypertelorism, a broad nasal root, a large and bifid nasal tip, and widow's peak. [orpha.net]

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]

As such there is information and no consensus in the published literature regarding the epidemiological statistics. [wikivisually.com]

If a surgical correction is planned, this complete work-up prevents unexpected complications and complements the evaluation of paranasal deformities. [ncbi.nlm.nih.gov]

Before corrective surgery, eye drops and ointment are critical to keep the eye moist and prevent blindness if the child is unable to close their eye. [hopkinsallchildrens.org]

To prevent these complications, an implant made out of alloplastic material could be considered. Implants take less surgery time, are limitlessly available and may have more favorable characteristics than autografts. [en.wikipedia.org]

Religious factors and social customs prevent detailed postmortem examination to study the various internal malformations. This is a severe handicap in learning and understanding the entire spectrum of embryological and structural defects. 1. [ruralneuropractice.com]

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3. Uz E, Alanay Y, Aktas D, Vargel I, et al. Disruption of ALX1 causes extreme microphthalmia and severe facial clefting: expanding the spectrum of autosomal-recessive ALX-related frontonasal dysplasia. Am J Hum Genet. 2010;86:789–796.
4. Twigg SRF, Versnel SL, Nurnberg G, et al. Frontorhiny, a distinctive presentation of frontonasal dysplasia caused by recessive mutations in the ALX3 homeobox gene. Am J Hum Genet. 2009;84:698–705.
5. Kayserili H, Uz E, Niessen C, et al. ALX4 dysfunction disrupts craniofacial and epidermal development. Hum Mole Genet. 2009;18:4357–4366.
6. Wu E, Vargevik K, Slavotinek AM. Subtypes of frontonasal dysplasia are useful in determining clinical prognosis. Am J Med Genet A. 2007;143A:3069–3078.
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11. Tessier P. Anatomical classification of facial, craniofacial, and lateral facial clefts. J Maxillofac Surg. 1976;14:69–92.
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13. Taybi H. Pediatric Surgery. 2nd ed. Chicago, IL: Year Book Medical; 1983. Radiology of syndromes and metabolic disorders; p. 235.
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