[Embryology] Chapter 17 — Head and Neck Clinical Correlates

"Ectopic thymic tissue"

"Glandular tissue that may persist along the migration pathway of the thymus, since pouch-derived tissue migrates extensively during development."

"Ectopic parathyroid tissue"

"Inferior parathyroid glands are especially variable in position; may remain in the neck or be found at the bifurcation of the common carotid artery."

"Branchial (external) fistula"

"Occurs when the second pharyngeal arch fails to grow caudally over the third and fourth arches, leaving remnants of the second, third, and fourth clefts in contact with the surface by a narrow canal, found anterior to the sternocleidomastoid muscle."

"Lateral cervical cyst"

"A remnant of the cervical sinus, most often found just below the angle of the jaw; often not visible at birth but enlarges during childhood; drained by a branchial fistula."

"Internal branchial fistula"

"A rare fistula occurring when the cervical sinus connects to the pharynx lumen via a small canal, usually opening in the tonsillar region; results from rupture of the membrane between the second pharyngeal cleft and pouch."

"Preauricular fistula"

"A fistula occurring in the region near the external ear, related to abnormal development of the first pharyngeal cleft/arch structures."

"Neural crest craniofacial defects"

"Disruption of neural crest cell development results in craniofacial malformations; because crest cells also form the conotruncal endocardial cushions, craniofacial defects often co-occur with cardiac defects."

"Persistent truncus arteriosus"

"A cardiac defect that can co-occur with craniofacial defects due to shared neural crest cell disruption affecting the conotruncal endocardial cushions."

"Treacher Collins syndrome"

"Mandibulofacial dysostosis; a rare autosomal dominant disorder (1/50,000 births, 60% new mutations) with hypoplasia of the maxilla, mandible, and zygomatic arches, cleft palate, external ear defects with conductive hearing loss, down-slanting palpebral fissures, and lower eyelid colobomas; caused by TCOF1 mutations."

"TCOF1 gene / treacle protein"

"Gene mutated in most Treacher Collins syndrome cases; its product, treacle, is a nucleolar protein necessary for preventing apoptosis and maintaining proliferation in neural crest cells."

"Robin sequence"

"A triad of micrognathia, cleft palate, and glossoptosis (posteriorly placed tongue), occurring in approximately 1/8,500 births; may be genetic, environmental, or a deformation from oligohydramnios."

"22q11.2 deletion syndrome"

"The most common deletion syndrome in humans, occurring in about 1/4,000 births, caused by a deletion on the long arm of chromosome 22 (or TBX1 mutation without deletion); includes DiGeorge syndrome, velocardiofacial syndrome, Shprintzen syndrome, conotruncal anomaly face syndrome, and congenital thymic aplasia/hypoplasia."

"DiGeorge syndrome/anomaly"

"A presentation within the 22q11.2 deletion spectrum, presenting with congenital heart and aortic arch defects, thymic hypoplasia/aplasia causing immune dysfunction, and hypocalcemia from parathyroid defects."

"Velocardiofacial syndrome"

"A presentation within the 22q11.2 deletion spectrum with mild facial dysmorphology, malar hypoplasia, micrognathia, prominent upper lip, and large ears."

"TBX1 gene"

"A gene within the 22q11.2 deletion interval; mutations in this gene alone can result in the same syndrome without a chromosomal deletion; variability in its regulation may explain the wide range of phenotypes seen."

"Hemifacial microsomia (Goldenhar syndrome)"

"Also called oculoauriculovertebral spectrum; includes small/flat maxillary, temporal, and zygomatic bones, plus ear (anotia, microtia), eye, and vertebral defects; asymmetry present in 65% of cases; occurs in 1/5,600 births; 50% have cardiac defects such as tetralogy of Fallot."

"Thyroglossal cyst"

"A cystic remnant of the thyroglossal duct that may lie anywhere along the thyroid's migratory pathway but is always near or in the midline of the neck; about 50% are close to or just inferior to the hyoid bone."

"Thyroglossal fistula"

"A fistulous canal connecting a thyroglossal cyst to the outside; usually arises secondarily after cyst rupture but may be present at birth."

"Aberrant thyroid tissue"

"Thyroid tissue found anywhere along the normal path of thyroid descent, commonly at the base of the tongue behind the foramen cecum; subject to the same diseases as the normal thyroid gland."

"Cleft lip (anterior to incisive foramen)"

"Includes lateral cleft lip, cleft upper jaw, and cleft between the primary and secondary palates; due to partial or complete lack of fusion of the maxillary prominence with the medial nasal prominence on one or both sides."

"Cleft (secondary) palate"

"A cleft posterior to the incisive foramen, including cleft palate and cleft uvula; results from lack of fusion of the palatine shelves due to shelf smallness, failure to elevate, inhibited fusion, or failure of the tongue to drop (as in micrognathia)."

"Van der Woude syndrome"

"The most common syndrome associated with cleft lip with or without cleft palate; autosomal dominant, caused by mutations in IRF6 (1p32-41); 88% of affected infants have lower lip pits."

"Oblique facial cleft"

"Produced by failure of the maxillary prominence to merge with its corresponding lateral nasal prominence along the nasolacrimal groove line, usually exposing the nasolacrimal duct to the surface."

"Median (midline) cleft lip"

"A rare abnormality caused by incomplete merging of the two medial nasal prominences in the midline; often accompanied by cognitive impairment and brain abnormalities."

"Holoprosencephaly (facial/midline)"

"Extensive deficiency of midline tissue causing fusion of the lateral ventricles; can be caused by SHH mutations, altered cholesterol biosynthesis, or maternal teratogen exposure (e.g., alcohol) during the third week of development."

"Synophthalmia"

"Fusion of the eyes due to extensive loss of midline facial tissue, seen in severe holoprosencephaly."

"Proboscis"

"A single nasal opening formed from fusion of the lateral nasal processes, seen in severe holoprosencephaly with extensive midline tissue loss."

"Cleft lip epidemiology"

"Cleft lip with or without cleft palate occurs in about 1/700 births, more frequently in males (65%); Asians and Native Americans have the highest rates (3.5/1,000), African Americans the lowest (1/1,000)."

"Isolated cleft palate epidemiology"

"Occurs in about 1/1,500 births, more often in females (55%); in females, palatal shelves fuse about 1 week later than in males."

"Valproic acid (teratogenic cause of orofacial clefts)"

"An anticonvulsant medication associated with increased risk of orofacial clefts when taken during pregnancy."

"Cigarette smoking (orofacial cleft risk factor)"

"Smoking during pregnancy increases the risk of having a baby with orofacial clefts."

"Natal teeth"

"Teeth that have erupted by the time of birth, usually involving the mandibular incisors; may be abnormally formed with little enamel."

"Tooth discoloration from tetracyclines"

"Teeth may be discolored by foreign substances such as tetracyclines taken during tooth development."

"Enamel deficiency from vitamin D deficiency (rickets)"

"A condition affecting tooth enamel formation caused by vitamin D deficiency during development."

"Pharyngeal cleft remnants — cervical cysts/fistulas"

"In some cases, remnants of the pharyngeal clefts remain as cervical cysts and/or fistulas after failing to be fully occluded by second arch overgrowth."

"Tetralogy of Fallot (neural crest-associated)"

"A cardiac defect cited as an example of the cardiac abnormalities that can accompany craniofacial neural crest defects, since crest cells contribute to the conotruncal endocardial cushions; also seen in hemifacial microsomia (50% of cases)."

"Transposition of the great vessels (neural crest-associated)"

"A cardiac defect cited as an example of outflow tract malformation resulting from disrupted neural crest cell contribution to the conotruncal endocardial cushions."

"Anotia and microtia"

"Absent (anotia) or small (microtia) external ear, seen as part of the hemifacial microsomia/Goldenhar syndrome spectrum of craniofacial abnormalities."

"Psychiatric illness in 22q11.2 deletion syndrome"

"Individuals with 22q11.2 deletion syndrome are more likely later in life to develop mental illnesses, including schizophrenia and depression."

"Retinoic acid embryopathy (Treacher Collins phenocopy)"

"Phenocopies of Treacher Collins syndrome can be produced in laboratory animals following exposure to teratogenic doses of retinoic acid, suggesting some human cases may be teratogen-induced rather than genetic."

"Cleft uvula"

"A mild posterior cleft defect, representing the least severe end of the cleft (secondary) palate spectrum."

"Cleft upper jaw"

"An anterior cleft defect in which the maxilla is split between the lateral incisor and the canine tooth, often extending to the incisive foramen."

"Micrognathia"

"Abnormally small mandible; the primary defect in Robin sequence, leading to a posteriorly placed tongue that prevents palatal shelf fusion."

"Glossoptosis"

"Posteriorly placed tongue, one component of the Robin sequence triad, resulting from poor mandibular growth."

"Bilateral conductive hearing loss (Treacher Collins)"

"Results from external ear defects, atresia of the auditory canals, and abnormalities of the middle ear ossicles in Treacher Collins syndrome."