McGillivray syndrome

Overview

McGillivray syndrome, also known as Frontonasal dysplasia type 1 or Frontonasal dysostosis, is a rare congenital condition characterized by distinctive craniofacial malformations resulting from abnormal development of the frontonasal process during embryogenesis. First documented by Iain McGillivray and colleagues, this syndrome affects the central portion of the face and skull and is typically evident at birth.

The condition varies in severity and may involve hypertelorism (wide-spaced eyes), broad nasal root, cleft lip and/or palate, and abnormalities of the forehead and hairline. Though typically isolated to craniofacial structures, some individuals may also present with neurological or ocular complications. McGillivray syndrome can occur sporadically or be inherited in an autosomal dominant or recessive fashion, depending on the genetic cause.

Causes

McGillivray syndrome is caused by disruptions in the normal embryological development of the frontonasal prominence, a key structure that forms the central midface. Several genetic factors may contribute to this disruption:

• Genetic mutations: Mutations in genes involved in craniofacial development, such as ALX1, ALX3, and ALX4, have been implicated in different types of frontonasal dysplasia, including McGillivray syndrome.

• Inheritance patterns: Depending on the gene involved, the condition may be inherited in an autosomal dominant or autosomal recessive manner. However, many cases are sporadic, occurring with no family history due to new (de novo) mutations.

Environmental and unknown factors may also play a role in some cases, but no definitive non-genetic cause has been established.

Symptoms

The clinical features of McGillivray syndrome are primarily craniofacial and are apparent at birth. The severity of these anomalies can vary significantly between individuals. Common signs and symptoms include:

• Hypertelorism: Abnormally wide-set eyes, often with a broad nasal root.

• Broad and flat nasal bridge: Often extending to the forehead, contributing to a characteristic facial appearance.

• Midline facial clefts:

  • Median cleft lip and/or cleft palate

  • May extend into the nose or forehead in severe cases

• Abnormal hairline: Low-set or unusual anterior hairline patterns.

• Nasal anomalies: Bifid nose or underdeveloped nasal tip.

• Skull anomalies: Frontal bossing (prominent forehead), possible craniosynostosis (early fusion of skull bones in some cases).

• Ocular findings:

  • Telecanthus (increased distance between the inner corners of the eyes)

  • Coloboma (notch or defect in the eyelid or iris in rare cases)

Most individuals have normal intellectual development, but rare cases may involve neurological issues if associated brain abnormalities are present.

Diagnosis

Diagnosis of McGillivray syndrome is primarily clinical, based on the distinctive craniofacial features observed at birth. Diagnostic steps include:

• Physical examination: Identification of key facial anomalies such as hypertelorism, broad nasal root, and clefts.

• Craniofacial imaging:

  • CT or MRI of the skull and brain to assess bone structure and rule out intracranial anomalies.

• Genetic testing:

  • Targeted sequencing of genes associated with frontonasal dysplasia (e.g., ALX1, ALX3, ALX4).

  • Chromosomal microarray to detect larger deletions or duplications if a single-gene mutation is not found.

• Ophthalmologic evaluation: To assess for vision anomalies or coloboma.

• ENT evaluation: For cleft palate or airway assessment if nasal abnormalities impair breathing.

A multidisciplinary team often plays a role in evaluating and confirming the diagnosis, including specialists in genetics, craniofacial surgery, and pediatrics.

Treatment

There is no cure for McGillivray syndrome, but many of the physical manifestations can be corrected or improved through surgery and supportive therapies. Treatment is highly individualized based on severity and may include:

• Surgical reconstruction:

  • Correction of cleft lip and palate, often performed in infancy or early childhood

  • Reconstructive procedures for nasal and forehead abnormalities

  • Skull surgery if craniosynostosis is present

• Speech therapy: For children with cleft palate or associated speech difficulties.

• Orthodontic care: Dental realignment may be necessary as part of the cleft repair process.

• Psychosocial support: Counseling for self-esteem and social challenges, especially in visible facial difference cases.

• Regular follow-up: Monitoring of growth, development, and potential need for additional surgical interventions during adolescence.

A coordinated team approach is essential, often involving craniofacial surgeons, ENT specialists, geneticists, speech therapists, and psychologists.

Prognosis

The prognosis for individuals with McGillivray syndrome varies based on the severity of the craniofacial anomalies and whether additional complications are present. In general:

• Most individuals have a normal life expectancy.

• Intellectual development is usually normal, unless neurological anomalies exist.

• Early surgical interventions and supportive care can significantly improve function and appearance.

• Cosmetic concerns and social adaptation may require long-term support.

With timely and comprehensive care, most individuals with McGillivray syndrome can lead healthy, fulfilling lives. Genetic counseling is recommended for families, particularly if a specific mutation is identified.