Syndromes

💡MASTER COMPARISON TABLE

💡SYNDROMES ASSOCIATED WITH MISSING OR
SUPERNUMERARY TEETH

💡Hypohidrotic ectodermal dysplasia

A hereditary disorder affecting ectoderm-derived structures, particularly teeth, hair, skin and sweat glands.

Clinical features

Genetics

• Genes include EDA, EDAR, EDARADD and WNT10A.

Dental management

• Early assessment of missing teeth.
• Removable prostheses can improve appearance, function and psychosocial wellbeing.
• Growth and jaw development should be monitored.
• Implant treatment, if considered, depends on age, skeletal development and individual circumstances.
• The classic X-linked form is associated with EDA.
• Other forms may have different inheritance patterns.

💡Cleidocranial dysplasia

A genetic skeletal disorder affecting intramembranous ossification, particularly the skull and clavicles, with characteristic dental abnormalities.

Genetics

• Gene: RUNX2.
• Usually autosomal dominant.

Clinical and skeletal features

• Delayed closure of fontanelles and cranial sutures.
• Frontal bossing.
• Hypoplastic or absent clavicles.
• Narrow, sloping shoulders that may be approximated toward the midline.
• Short stature may occur.

Dental findings

• Retained primary teeth.
• Delayed eruption of permanent teeth.
• Multiple unerupted permanent teeth.
• Numerous supernumerary teeth.
• Crowding and abnormal eruption pathways.

Management

• Multidisciplinary dental and orthodontic planning.
• Surgical exposure and orthodontic traction may be considered.
• Treatment is individualized because multiple supernumerary teeth and delayed eruption can make rehabilitation complex.

Exam pearl: RUNX2 mutation + absent clavicles + multiple supernumerary teeth = cleidocranial dysplasia.

💡Gardner syndrome

Gardner syndrome is a phenotypic form of familial adenomatous polyposis (FAP) associated with extracolonic manifestations.

Genetics

• Gene: APC.
• Autosomal dominant inheritance.

Features

Clinical importance

Jaw osteomas or unusual dental findings can precede recognition of intestinal polyposis.

FCPS tip: Multiple jaw osteomas + impacted/supernumerary teeth + intestinal polyposis = Gardner syndrome. The major concern is the associated colorectal cancer risk, requiring medical/genetic evaluation.

💡CRANIOSYNOSTOSIS SYNDROMES

Craniosynostosis is premature fusion of one or more cranial sutures, resulting in characteristic skull and facial deformities.

💡Crouzon syndrome

Genetics

• Usually associated with FGFR2 variants.
• Autosomal dominant.

Clinical features

• Craniosynostosis.
• Midface hypoplasia and retrusion.
• Shallow orbits and proptosis.
• Beaked or convex facial profile.
• Relative mandibular prognathism due to midface deficiency.
• High-arched palate and dental crowding.
• Airway obstruction may occur.

Key discriminator

Hands and feet are usually normal in classic Crouzon syndrome.

💡Apert syndrome

Genetics

• Usually associated with FGFR2 variants.
• Autosomal dominant; many cases arise from a new pathogenic variant.

Clinical features

• Craniosynostosis.
• Midface hypoplasia and proptosis.
• High-arched palate; cleft palate may occur.
• Dental crowding and malocclusion.
• Syndactyly of the hands and feet, often with a mitten-like appearance.

💡Crouzon versus Apert

MCQ tip: Both syndromes can feature proptosis and midface hypoplasia. Use the limb findings to distinguish them.

💡Pfeiffer syndrome

Pfeiffer syndrome is another craniosynostosis syndrome.

Genetics

• Associated with FGFR2 or, in some forms, FGFR1 variants.

Features

• Craniosynostosis.
• Midface hypoplasia.
• Broad, medially deviated thumbs.
• Broad great toes.
• Variable syndactyly.

Exam distinction

Remember: Craniosynostosis + broad thumbs/great toes = Pfeiffer syndrome.

💡FIRST/SECOND ARCH PATTERNS

💡Pierre Robin sequence

Pierre Robin is a sequence, not necessarily a single-gene syndrome. One developmental abnormality initiates a cascade of secondary changes.

Classic sequence

Clinical features

• Micrognathia.
• Glossoptosis.
• Upper-airway obstruction.
• U-shaped cleft palate is common, but not required for diagnosis.
• Feeding difficulty and aspiration risk may occur.

Pierre Robin sequence may occur alone or as part of another syndrome, including Stickler syndrome or Treacher Collins syndrome.

FCPS tip: Micrognathia + glossoptosis + airway obstruction = Pierre Robin sequence.

💡Treacher Collins syndrome

Treacher Collins syndrome is a craniofacial disorder caused by abnormal development of structures derived largely from the first and second pharyngeal arches.

Genetics

• Commonly associated with TCOF1.
• POLR1D and POLR1C are additional associated genes.

Clinical features

Dental relevance

• Malocclusion.
• Abnormal mandibular development.
• Palatal abnormalities.
• Airway and feeding concerns may complicate dental care.

Treacher Collins versus Pierre Robin

Broader comparison

💡CHROMOSOMAL AND 22q11.2 DISORDERS

💡Down syndrome

Down syndrome is caused by additional chromosome 21 genetic material, most commonly full trisomy 21.

Genetic forms

• Free trisomy 21: most common.
• Robertsonian translocation.
• Mosaicism.

Clinical features

Oral and dental findings

• Delayed eruption.
• Hypodontia and microdontia.
• Relative macroglossia or a protruding/fissured tongue.
• Malocclusion.
• Increased periodontal disease susceptibility.
• Taurodontism may occur.

FCPS tip: Flat facial profile + upslanting palpebral fissures + hypotonia + single palmar crease = Down syndrome. The chromosomal association is trisomy 21.

💡DiGeorge syndrome — 22q11.2 deletion syndrome

DiGeorge syndrome is part of the 22q11.2 deletion spectrum, caused by a microdeletion that commonly includes TBX1.

Developmental basis

Abnormal development of the third and fourth pharyngeal pouches contributes to thymic and parathyroid abnormalities.

Classic clinical pattern

Oral and dental findings

• Cleft or submucous cleft palate.
• Velopharyngeal insufficiency.
• Bifid uvula may occur.
• Dental and craniofacial abnormalities can be present.

Why does hypocalcemia occur?

Parathyroid hypoplasia reduces PTH secretion, which lowers serum calcium.

FCPS tip

22q11.2 deletion + conotruncal heart defect + thymic deficiency + hypocalcemia = DiGeorge syndrome.

💡Turner syndrome

Turner syndrome results from complete or partial absence of one X chromosome, classically 45,X.

Clinical features

• Short stature.
• Webbed neck.
• Low posterior hairline.
• Broad or shield-shaped chest with widely spaced nipples.
• Lymphedema, particularly in infancy.
• Gonadal dysgenesis and delayed puberty.

Exam distinction

A webbed neck is a strong clue to Turner syndrome. A flat facial profile, upslanting palpebral fissures and a single transverse palmar crease favor Down syndrome.

Other chromosomal disorders

ORAL-FACIAL-DIGITAL AND HAMARTOMA SYNDROMES

💡Oral-facial-digital syndrome

Oral-facial-digital syndromes form a heterogeneous group affecting the oral cavity, face and digits.

Type I

• Associated with OFD1.
• Usually X-linked dominant and classically often lethal in males.
• Polycystic kidney disease may occur.

Clinical findings

FCPS tip: Bifid tongue + multiple oral nodules + hyperplastic frenula + digital anomalies = oral-facial-digital syndrome.

💡Cowden syndrome — PTEN hamartoma tumor syndrome

Cowden syndrome is an inherited hamartoma syndrome associated with increased cancer risk.

Genetics

• PTEN pathogenic variant.
• Usually autosomal dominant.

Clinical features

Oral relevance

Multiple oral papillomas may produce a cobblestone-like appearance of the mucosa.

FCPS tip: Oral papillomas + macrocephaly + multiple hamartomas + breast/thyroid/endometrial tumor risk = Cowden syndrome.

💡Peutz–Jeghers syndrome

Genetics

• STK11 pathogenic variant.
• Autosomal dominant.

Key features

• Mucocutaneous pigmentation, especially around the lips and oral mucosa.
• Gastrointestinal hamartomatous polyps.
• Increased risk of several malignancies.

Cowden versus Peutz–Jeghers

💡OTHER SYSTEMIC ASSOCIATIONS

💡Osteogenesis imperfecta

Osteogenesis imperfecta is a genetic connective-tissue disorder characterized by bone fragility, commonly involving type I collagen.

Genetics

• Commonly associated with COL1A1 or COL1A2 variants.

Clinical features

Dental association: dentinogenesis imperfecta

• Opalescent teeth.
• Blue-gray or amber discoloration.
• Bulbous crowns with cervical constriction.
• Enamel fracture due to poor dentin support.
• Short roots and pulp obliteration may occur.

💡Gorlin syndrome

Gorlin syndrome, also known as nevoid basal cell carcinoma syndrome, is associated with PTCH1 pathway abnormalities.

Key features

• Multiple odontogenic keratocysts.
• Multiple basal cell carcinomas.
• Palmar and plantar pits.
• Bifid ribs.
• Calcification of the falx cerebri.

Exam distinction: Multiple jaw keratocysts suggest Gorlin syndrome; multiple jaw osteomas plus intestinal polyposis suggest Gardner syndrome.

💡McCune–Albright syndrome

A mosaic disorder caused by an activating GNAS variant.

Classic triad

1. Polyostotic fibrous dysplasia.
2. Café-au-lait pigmentation.
3. Endocrine hyperfunction, such as precocious puberty.

Oral and maxillofacial relevance

Craniofacial fibrous dysplasia may cause facial asymmetry, bone expansion and a ground-glass radiographic appearance.

💡Goldenhar syndrome — oculo-auriculo-vertebral spectrum

Goldenhar syndrome is a developmental disorder affecting the face, ears and vertebral structures, often asymmetrically.

Clinical features

• Facial asymmetry.
• Mandibular hypoplasia, often unilateral.
• Microtia or other ear abnormalities.
• Preauricular tags.
• Epibulbar dermoid.
• Vertebral anomalies.

Goldenhar versus Treacher Collins