Edit concept Question Editor Create issue ticket

Frontonasal Dysplasia

Median Cleft Syndrome

Frontonasal dysplasia is a rare abnormality involving the forehead, nose, and eyes. Other names for this condition include median cleft syndrome, frontonasal syndrome and frontonasal dysostosis. It is noticed at birth although a few cases have been diagnosed antenatally. It can occur sporadically but autosomal dominant, autosomal recessive, and X-linked patterns have also been reported.


Presentation

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.

Thin Skin
  • She later presented with a palpable bone graft prominence, associated contour deformity, and an area of overlying paper-thin skin at the nasal tip. Although there was no ulceration, the threat of graft extrusion required immediate attention.[ncbi.nlm.nih.gov]
Ulcer
  • Although there was no ulceration, the threat of graft extrusion required immediate attention. The prominent bone graft tip was debrided, and the overlying soft tissue envelope was augmented using acellular dermal matrix.[ncbi.nlm.nih.gov]
Partial Alopecia
  • We here report on a female patient presenting with severe FND features along with partial alopecia, hypogonadism and intellectual disability.[ncbi.nlm.nih.gov]
Eruptions
  • Because of this, correction in later patients was delayed until after eruption of permanent maxillary incisors. The mean anterior interorbital distance was reduced in patients from 184 percent to 98 percent of sex-matched controls.[doi.org]
High Nasal Root
  • We report a Brazilian girl, born to normal and non-consanguineous parents and presenting, among other signs, brachyacrocephaly, a wide forehead, hypertelorism, wide palpebral fissures with multiple eyelid colobomas, a broad and high nasal root, an absent[ncbi.nlm.nih.gov]
Carp-Like Mouth
  • […] non-consanguineous parents and presenting, among other signs, brachyacrocephaly, a wide forehead, hypertelorism, wide palpebral fissures with multiple eyelid colobomas, a broad and high nasal root, an absent nasal tip, a wide columella, a long and smooth philtrum, a carp-like[ncbi.nlm.nih.gov]

Workup

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].

Posterior Fossa Cysts
  • We describe a boy with frontonasal "dysplasia"; cerebral anomalies, including agenesis of corpus callosum and probable Dandy-Walker malformation (absent superior vermis, hypoplastic cerebellum and brain stem, and possible posterior fossa cyst in this[ncbi.nlm.nih.gov]

Treatment

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

Prognosis

  • The results suggest that cases with FND should be evaluated for additional anomalies, as these may help to determine prognosis.[ncbi.nlm.nih.gov]
  • 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]
  • Genetic counseling was provided, and the prognosis and appropriate treatment strategies were explained to the parents. Genetic analysis revealed that the patient had a normal ALX3 gene sequence, indicating a sporadic occurrence of FND ( Table 1 ).[ncbi.nlm.nih.gov]

Etiology

  • 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]
  • Group I had 12 individuals with isolated form and Group II had 6 individuals with FD syndromic with unknown etiology. The results are presented in set.[ncbi.nlm.nih.gov]
  • The etiology of FND remains uncertain. While multifactorial inheritance has been proposed, parental consanguinity with young parental age in the present case cannot exclude autosomal recessive inheritance.[ncbi.nlm.nih.gov]
  • Frontonasal dysplasia is an etiologically heterogeneous development alteration including a set of anomalies affecting the eyes, forehead, and nose as a result of a malformation of the frontonasal elevation.[ncbi.nlm.nih.gov]
  • Etiology The aetiology is still unknown, but seems to be linked to defective embryologic development of the nasal capsule. Antenatal diagnosis Hypertelorism, cleft lip and encephalocele can be detected by antenatal ultrasound.[orpha.net]

Epidemiology

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

Prevention

  • 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]
  • 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.[ncbi.nlm.nih.gov]
  • 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]

References

Article

  1. Koçak H, Ceylaner G. Frontonasal dysplasia: a family presenting autosomal dominant inheritance pattern. Genet Couns. 2009;20:63–68.
  2. Nevin NC, Leonard AG, Jones B. Frontonasal dysostosis in two successive generations. Am J Med Genet. 1999;87:251–253.
  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.
  7. Kean J, Al-Busaidi SSM, Quaba AA. A case report of frontonasal dysplasia. Int J Pediatr Otorhinolaryngol. 2010;74:306–308.
  8. Martinelli P, Russo R, Agangi A, Paladini D. Prenatal ultrasound diagnosis of frontonasal dysplasia. Prenatal Diagn. 2002;22:375–379.
  9. DeMyer W. The median cleft face syndrome: differential diagnosis of cranium bifidum occultum, hypertelorism, and median cleft nose, lip and palate.Neurology. 1963;17:961–971
  10. Sedano HO, Cohen MM, Jirasek J, Gorlin RJ. Frontonasal dysplasia.J Pediatr. 1970;76:906–913.
  11. Tessier P. Anatomical classification of facial, craniofacial, and lateral facial clefts. J Maxillofac Surg. 1976;14:69–92.
  12. Esmer AC, Kalelioglu I, Kayserili H, et al. Prenatal diagnosis of frontonasal dysplasia with anterior encephalocele. J. Turk Ger Gynecol Assoc. 2003;14(1): 50-52
  13. Taybi H. Pediatric Surgery. 2nd ed. Chicago, IL: Year Book Medical; 1983. Radiology of syndromes and metabolic disorders; p. 235.
  14. Fox JW, Golden GT, Edgerton MT. Frontonasal dysplasia with alar clefts in two sisters. Genetic considerations and surgical correction. Plast Reconstr Surg. 1976;57:553–556

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2019-06-28 10:53