Etiology:

• It is a rare autosomal dominant congenital disorder characterized by craniofacial deformities
• Associated with TCOF-1 gene (treacle gene) chromosome 5 mutation
• Due to stapedial artery defects, growth of craniofacial structures derived from the first and second pharyngeal arch, groove, and pouch are diminished symmetrically and bilaterally

Clinical:

1. Facial features:

• Downward slopping of palpebral features
• Underdeveloped zygomatic-maxillary complex
• Colobomas of lower eyelid (missing piece of tissue)
• Middle ear atresia
• Lower set ears with deformed pinna
• Orofacial clefts

2. Oral features:

• Macrostomia
• Cleft palate
• High arched palate
• Open bite (apertognathia)
• Mandible hypoplasia

Prenatal diagnosis:

• Mutations can be detected in chorionic villus sampling or amniocentasis
• Ultrasonography to detect craniofacial abnormalities later in pregnancy

X-ray:

• Decreased slopping of orbital floor
• Aplasia/ hypoplasia of zygoma
• Obtuse mandible angle
• Lateral cephalogram:
  • Broad curve of mandible
  • Flat condylar and coronoid process

Management:

• Hearing aids
• Surgery – Ophthalmological, maxillofacial, orthodontic

Prognosis:

• Treacher Collins syndrome patients grow to become functioning adults with normal intelligence. With proper management, life expectancy is approximately the same as in the general population

Differential diagnosis:

• Nager syndrome (acrofacial dysostosis) – distinguished by limb preaxial defects
• Miller syndrome – distinguished by limb postaxial defects
• Burn-Mckeown syndrome

AKA Encephalotrigeminal angiomatosis

NOTE: Not a genetic condition, mutation is somatic and occurs before birth.

Port wine stain on forehead, scalp or around eyes due to over abundance of capillaries near surface of skin.

Clinical:

• Triad:
  • Facial port wine nevus
  • Leptomeningeal angiomatosis
  • Glaucoma
• Contralateral hemiplegia
• Gingival overgrowth
• Multiple impactions
• Seizure disorder, mental retardation

Stevens-Johnson syndrome

NOTE: Not a genetic condition, caused by body reaction to certain medication

• Erythema multiforme in oral mucosa
• Photophobia
• Conjunctivitis
• Corneal ulceration
• Genital ulceration

Von Recklinghausen neurofibromatosis

Wide spread thickening of nerves due to tumors forming within them

Etiology:

Mutations of NF1 and NF2 genes:

• 50% spontaneous
• 50% AD

Clinical:

• Oral – Neurofibromas, macroglossia
• CNS – Malignancies, retardation
• Skin – Café au lait spots – can turn malignant
• Multiple schwannomas, neurilemmomas, neurinomas
• Nerves are thick – form elliptical buldges
• Generalized tumors commonly distributed on arms, legs, chest, back, neck

Management:

• Excision of selected tumors – if symptomatic/unsightly

Etiology:

Zoster infection of geniculate ganglion

Clinical:

• Facial paralysis
• Severe pain of EAM and pinna
• Vesicular eruptions along a dermatome

Management:

• Antiviral therapy
• Corticosteroids

Peutz Jegher Syndrome

Etiology:

• AD

Clinical:

• Hereditary intestinal polyposis
• Pigmentation of face and oral cavity
• GIT adenocarcinoma

Histology:

• Melanin granules in basal layer of mucosa

Plummer Vinson Syndrome

• AKA Paterson-Kelly syndrome
• Precancerous lesion
• Angular cheilitis
• Dysphagia due to oesophageal webs
• Filiform papillae atrophy
• Koilonychia

It is a set of abnormalities affecting the head and neck. It is described as a “sequence” because one of its features, underdevelopment of the lower jaw (mandible), sets off a sequence of events before birth that cause the other signs and symptoms.

Etiology:

• Associated with restriction of mandibular development in utero
• Associated with mutations in chromosomes 2, 11, and 17
• An affliction in the family increases the chance of another

Pathogenesis:

Mechanical theory – mandibular hypoplasia, the initial event occurs between the 7th and 11th week of gestation. This keeps the tongue high in the oral cavity, causing a cleft in the palate by preventing the closure of the palatal shelves

Clinical:

• Triad:
• U-shaped cleft palate
• Micrognathia of mandible
• Glossoptosis (tongue that is placed further back than normal)
• Airway obstruction due to the tongue position leads to difficulty in breathing
• Malnutrition due to feeding difficulties in early life, and therefore are unable to grow and gain weight at the expected rate
• Hydrocephaly/microcephaly occasionally

Management:

• Airway management and optimizing breathing and feeding to improve growth nutrition
• Monitor sleep apnea. Patient should be placed in side lying or prone position. In severe refractory cases, can do oral airway placement, laryngeal mask or intubation (intubation performed by specialized physician)
• For feeding difficulties, can use nasogastric or orogasric feeding tube temporarily
• Palatal plates such as the pre-epiglottic baton plate, which have a velar extension, pulls the base of the tongue forward. This is helpful in the relief of airway obstruction, and it also facilitates the swallowing mechanism during feeding.
• In some children with pierre robin sequence, growth of the mandible catches up, and as adults these individuals have normal-sized chins.
• Residual deficit maybe corrected by surgery/ distraction osteogenesis

Prognosis:

• Mostly good, with proper management, PRS babies can grow to healthy normal adult life

Differential diagnosis:

• CHARGE syndrome
• Childhood sleep apnea
• DiGeorge syndrome
• Fetal alcohol syndrome
• Treacher collins syndrome

Etiology:

Generalized symmetrical increase in bone density

Classification:

Infantile:

• AR
• Bone pain
• Normocytic anemia + hepatosplenomehaly
  • Due to compensatory extramedullary hematopoiesis
• Delayed tooth eruption
• Facial deformity
• Optic nerve atrophy, blindness
• Deafness
• Facial paralysis
• Pathological fractures
• Osteomyelitis
• Pancytopenia and all its symptoms

Adult:

• AD
• Mild, not fatal
• Bone pain

Diagnosis:

X-ray:

• Cotton wool appearance – bone within bone

Histology:

• Cancellous bone replaced by tortuous lamellar bone
• Amorphous bone deposits in marrow (no medullary space)
• Osteophytic bone transformation

Management:

• Frequent prophylaxis
• Home care
• Topical fluorides
• Bone marrow transplants + high dose calcitriol
• Symptomatic management for teeth

Complication:

• Osteomyelitis

Picture

Defective ground substance and laying down of collagen, therefore not mineralized

Etiology:

• AD – Defect in biosynthesis of collagen 1
• Mutations in structural gene for collagen proteins – ie. COL1A2 – same mutation causes dentinogenesis imperfecta

Clinical:

• Bone fragility (thin bones without cortex)
• Hearing loss
• Dentinogenesis imperfecta
• Blue sclera
• Opalescent dentine
• Spine deformities
• Joint hyperextensibility

Classification:

Diagnosis:

• Histology:
  • Decreased mass of cortical and cancellous bone
  • Bone architecture immature throughout life since woven bone does not mature to lamellar bone
• DNA based sequencing test
• X-ray

Management:

• Bisphosphonates
• Extensive restoration with full crown coverage
• ENT – correct hearing loss
• Physiotherapy/ surgery – kyphoscoliosis
• Intramedullary rodding – orthopedic management

Etiology:

Fibrillin gene (FBN1) mutation on chromosome 5 – low strength collagen

Clinical:

1. Musculoskeletal:

• Long extremities in relation to trunk
• Pectus carinatum or pectus excavatum
• Scoliosis

2. Orofacial:

• Long narrow face
• High arched palate
• Dental crowding

3. Cardiovascular:

• Mitral valve prolapse + medial necrosis of aorta – mitral and aortic regurgitation – aneurysm and heart failure

4. Optical:

• Ectopia lentis
• Myopia
• Retinal detachment

Management:

• Always use prophylaxis for infectious endocarditis
• Annual ECG, ophthalmic review and scoliosis screening

Etiology:

AD – PTCH gene mutation

Clinical:

1. Dental:

• KCOT (keratocystic odontogenic tumour) – benign intraosseous neoplasm of jaw

2. Skin:

• Basal cell carcinoma
• Dermal cysts
• Palmer planter keratosis

3. Eyes:

• Hypertelorism
• Internal strabismus

4. Bone:

• Bifid ribs
• Vertebral anomalies

5. CNS:

• Calcified flax cerebri
• Retardation

6. Reproductive:

• Hypogonadism

Diagnosis:

Criteria:

• 2 major
• 1 major and 2 minor

Minor:

• Microencephaly
• Ovarian fibroma
• Medulloblastoma
• Syndactyl

X-ray:

• Bridging of sella turica
• Vertebral anomalies
• Modelling defects of hands and feet

Management:

• Surgical + medical/photodynamic therapy