Treacher Collins Syndrome associated with severe Meibomian Gland Atrophy

 Treacher Collins Syndrome is a rare genetic mutation, primarily caused by changes (mutations) in the TCOF1 gene, but is also associated with mutations in the POLR1B, POLR1C or POLR1D genes. In the case of TCOF1 and POLR1B, the mode of inheritance is autosomal dominant, while for POLR1C it is autosomal recessive; (both autosomal dominant and recessive mutations in POLR1D have been reported in association with TCS). 

https://ccakids.org/treacher-collins-syndrome.html

Patients usually have craniofacial abnormalities often involving the underdevelopment of the zygomatic complex, cheekbones, jaws, palate, and mouth. This can  lead to breathing and feeding difficulties. In addition, affected individuals may also have malformations of the eyes including a downward slant of the opening between the upper and lower eyelids (palpebral fissures) and anomalies of external and middle ear structures, which may result in hearing loss. Dryness has been reported but no reports of severe meibomian gland atrophy have been published. 

I think this is the first report. Clearly the mutation is leading to an issue with the closure of the palpebra (eyelids) or a primary atrophy of the meibomian glands. 

Please let me know if you have have Treacher Collins Syndrome or know someone who has it. This should be formally reported.

SLC

jramirez@voeyedr.com

Treacher Collins Syndrome

Synonyms of Treacher Collins Syndrome

• Franceschetti-Zwalen-Klein syndrome
• mandibulofacial dysostosis
• TCS
• Treacher Collins-Franceschetti syndrome

General Discussion

Summary

Treacher Collins syndrome (TCS) is a rare genetic disorder characterized by distinctive abnormalities of the head and face. Craniofacial abnormalities tend to involve underdevelopment of the zygomatic complex, cheekbones, jaws, palate and mouth which can lead to breathing and feeding difficulties. In addition, affected individuals may also have malformations of the eyes including a downward slant of the opening between the upper and lower eyelids (palpebral fissures) and anomalies of external and middle ear structures, which may result in hearing loss. Brain and behavioral anomalies such as microcephaly and psychomotor delay have also been occasionally reported as part of the condition. The specific symptoms and physical characteristics associated with TCS can vary greatly from one individual to another. Some individuals may be so mildly affected as to go undiagnosed, while others may develop serious, life-threatening complications. TCS is primarily caused by changes (mutations) in the TCOF1 gene, but is also associated with mutations in the POLR1B, POLR1C or POLR1D genes. In the case of TCOF1 and POLR1B, the mode of inheritance is autosomal dominant, while for POLR1C it is autosomal recessive. In contrast, both autosomal dominant and recessive mutations in POLR1D have been reported in association with TCS.

Introduction

TCS is named after Edward Treacher Collins, a London ophthalmologist who first described the disorder in the medical literature in 1900. TCS is also known as mandibulofacial dysostosis or Treacher Collins-Franceschetti syndrome.

Signs & Symptoms

The symptoms and severity of TCS can vary dramatically from one person to another, even among members of the same family. Some individuals may be so mildly affected that they can go undiagnosed; others may have significant abnormalities and the potential for life-threatening respiratory complications. It is important to note that affected individuals will not have all of the symptoms discussed below.

The major characteristic features of TCS encompass certain bones of the face, ears and soft tissues around the eyes. Affected individuals present with distinctive facial features and potentially develop hearing and vision problems. The abnormalities of TCS are typically symmetric (almost identical on both sides of the face) and are present at birth (congenital). Speech and language development can be compromised by hearing loss, cleft palate or jaw and airway problems. Intelligence is usually unaffected but brain and behavioral anomalies such as microcephaly and cognitive delay have been reported infrequently as part of the condition.

Infants with TCS exhibit underdeveloped (hypoplastic) or absent cheekbones (malars), causing this area of the face to appear flat or sunken. The bone of the lower jaw (mandible) is incompletely developed (mandibular hypoplasia), causing the chin and the lower jaw to appear abnormally small (micrognathia). Certain bony structures (e.g., coronoid and condyloid processes) that anchor portions of the lower jaw bone to muscle can be unusually flat or absent. Affected infants may also exhibit underdevelopment of the throat (pharyngeal hypoplasia). Pharyngeal hypoplasia with underdevelopment of the lower jaw (mandibular hypoplasia) and/or abnormal smallness of the jaw (micrognathia) may contribute to feeding problems and/or breathing difficulties (respiratory insufficiency) during early infancy. Children may experience obstructive sleep apnea which is characterized by repeated short interruptions of normal breathing and air movement during sleep. In some severely-affected individuals, life-threatening respiratory difficulties may develop. (For more information on this condition, choose “Infantile Apnea” as your search term in the Rare Disease Database.)

Additional abnormalities that may contribute to respiratory or feeding difficulties include narrowing or obstruction of the nasal airways (choanal stenosis or atresia). Some children may be described as having features of “Pierre Robin sequence” which include severe micrognathia, a tongue that is displaced farther back in the mouth than normal (glossoptosis) with or without incomplete closure of the roof of the mouth (cleft palate). Even in patients where the palate fuses, it may remain high arched which can still affect feeding and respiration. In addition, malformations of the mouth and the jaw may result in dental abnormalities, such as teeth that are underdeveloped (hypoplastic) and/or misaligned (malocclusion). Additional dental abnormalities have also been reported including missing teeth (tooth agenesis), clouding or discoloration of the enamel of teeth (enamel opacity), and improper (ectopic) eruption of certain upper teeth (maxillary molars).

Individuals with TCS may develop hearing loss due to the failure of sound waves to be conducted through the middle ear (conductive hearing loss). Conductive hearing loss usually results from abnormalities affecting structures within the middle ear and individuals with TCS may also have malformed or absent ossicles, the three small bones through which sound waves are transmitted in the middle ear (i.e., incus, malleus, and stapes). In addition, the external ear structures are often absent, small or malformed (microtia), with narrowing (stenosis) or blockage (atresia) of the external ear canals. The outer ears may be crumpled or rotated. In contrast, the inner ear is usually unaffected, although malformation of the bony spiral organ in the inner ear (cochlea) and the structures within the inner ear that play a role in balance (vestibular apparatus) have been reported. Additional symptoms may include the presence of small growths of skin or pits just in front of the external ear (preauricular tags) and an abnormal passage that is closed on one end (blind fistula) that normally drains the ears to the nose.

Many infants with TCS have abnormalities of the tissue surrounding the eyes. These eye differences can give affected individuals a saddened facial appearance. The most common ocular symptom is a downward slant to the opening between the upper and lower eyelids (palpebral fissures). Additional symptoms include a lower eyelid notch or cleft of missing lid tissue (lid coloboma), partial absence of eyelashes on the lower eyelid, crossed eyes (strabismus) and narrowed tear ducts (dacrostenosis). Occasionally malformations of the globe are seen and can include notch or cleft of missing tissue of the iris or abnormally small eyes (microphthalmia). Vision loss may occur in some patients. The degree of visual impairment varies depending upon the severity and combination of ocular abnormalities. Lower eyelid abnormalities can cause the eyes to dry out, which increases the risk of chronic irritation and eye infections.

Approximately 5% of individuals with TCS display development deficits or neurological problems such as psychomotor delay. However, intelligence is generally unaffected with normal language development. Nonetheless, issues with speech development can occur because of hearing loss, cleft palate or difficulties producing sounds because of structural distortion. Some individuals with TCS exhibit additional physical abnormalities such as widely spaced eyes, notching of the upper eyelid, nasal deformity, an abnormally wide mouth (macrostomia), unusual growth of the scalp hair toward the cheeks, congenital heart defects and/or gastrointestinal malformation.