Presentation on theme: "A Review of Pediatric Syndromes"— Presentation transcript:
1 A Review of Pediatric Syndromes Jamie Tibbo, PGY-5Department of OtolaryngologyJuly 25, 2008
2 CHARGE Syndrome Autosomal Dominant Due to a mutation in DNA-binding protein-7 (CHD7) geneColoboma- posterior chamber(80%)Heart anomalies (85%)Atresia of choana (57%)Retardation- growth(80%) & mental (70%)Genital defects (in males)Ear anomalies (90-100%) & deafness(62%)Usually bilat and mixed hearing loss
3 DiGeorge SyndromeGenetic disorder due to microdeletion of Chromosome 22q11.2 (tbx-1 gene)The same genetic defect as VCF with different phenotypic expressionCharacterized by:Hypocalcemia (due to hypoplastic parathyroids)Immunodeficiency due to hypoplastic thymusCongenital heart defects of the outflow tracts (aorta and pulmonary artery).Reference:
4 Pendred Syndrome Autosomal recessive SNHL associated with iodine metabolism defect leading to euthyroid goiterThyroid abnormality detcted with a perchlorate discharge test (shows abnormal organification of nonorganic iodine)Temporal bone imaging often show Mondini malformation or enlarged VA’s
5 Treacher-Collins Syndrome (Mandibulofacial dysostosis) Autosomal dominant, 40% will have family history, other 60% new mutationsTCOF1 gene found on chromosome 5q (TREACLE gene)Malformation of 1st (& 2nd) branchial archesOtologic: Malformed ossicles, auricular deformity, aural atresia, CHL present 30% of time, occasional SNHL50% will have hearing impairment from EAC and/or middle ear malformationsPreauricular fistulas, mandibular and malar hypoplasia, antimongoloid palpebral fissures, coloboma of the lower eyelids, may have cleft lip and palate, normal IQ
6 Treacher-Collins Syndrome (Mandibulofacial dysostosis) Figure Treacher Collins syndrome. Zygomatic and mandibular hypoplasia, lower lid colobomas, and downslanting palpebral fissures.Reference: Bailey’s Otolaryngology-Head & Neck Surgery
7 Alport Syndrome 6 subtypes: 3 AR, 3 X-linked Progressive SNHL (usually 2nd decade)Varying degrees of renal disease (renal agenesis to mild renal dysplasia identifiable on ultrasound)Renal disease can be severe in men/boys
8 Apert (acrocephalosyndactyly) Autosomal dominant, most cases due to spontaneous mutationDue to a mutation of FGFR-2 (Fibroblast Growth Factor Receptor) gene (10q26)Common findings:Craniosynostosis (pre-mature fusion of the cranial sutures)Severe symmetrical syndactylyLow-set earsCognitive function normal to severe mental retardationEyes: down-slanting palpebrael fissures, Hypertelorism, ExophthalmosMidface hypoplasiaMandibular prognathismPossible cleft palateNose: Parrot-beaked nose, possible Choanal AtresiaSyndactyly and cervical fusion
9 Apert (acrocephalosyndactyly) Figure 99.4 Apert syndrome has the additional feature ofsyndactyly.Reference: Bailey’s Otolaryngology-Head & Neck Surgery
10 Crouzon Syndrome (Craniofacial Dysostosis) Autosomal dominant, 50% due to spontaneous mutations, complete penetrance, variable expresivityDue to mutation of FGFR-2 (Fibroblast Growth Factor Receptor) gene (10q26)Common findings:Craniosynostosis (pre-mature fusion of the cranial sutures)HypertelorismExophthalmosMidface hypoplasiaMandibular prognathismParrot-beaked noseNo Syndactyly or cervical fusionCognitive function normal to severe mental retardation
11 Branchiootorenal Syndrome (Melnick-Fraser Syndrome) Autosomal dominant, involves 8q between D8S87 and D8S165 (EYA1 gene)Branchial cleft anomalies (63%): cysts or fistulaeOtologic malformations:hearing loss (89%)preauricular pits (77%)auricle abnormalities (41%)ossicular & cochlear malformations2% of children with severe/profound SNHLRenal Dysplasia (66%)agenesis, polycystic kidneys, duplicated ureters; renal abnormalities identifiable on IVP or renal U/S
12 Branchiootorenal Syndrome (Melnick-Fraser Syndrome) Figure 99.6 Branchio-oto-renal syndrome. This 3-year-old boy has visible cup-ear deformities. He also has branchial cleft fistulae and only one kidney.Reference: Bailey’s Otolaryngology-Head & Neck Surgery
13 Down Syndrome Craniofacial Features: Brachycephaly Flat occiput Abnormal small earsUpslanting palpebral fissuresEpicanthic foldsShort small noseMidface hypoplasiaLarge fissured lipsLarge fissured tongueDental abnormalitiesShort neckAtlantoaxial subluxation & instability
14 Goldenhar Syndrome (Oculoauriculovertebral spectrum) Characterized by unilateral facial asymmetry, unilateral external & middle ear changes, vertebral malformationsOcular findings: upper lid colobomataOtologic findings: mildly deformed ears to anotia, EAC atresia, ossicular abnormalitiesUnderdevelopment of mandible, orbit, facial muscles, also may have hemivertebrae of vertebral columnHemifacial macrosomia often placed in this categoryMost cases sporadic, some autosomal dominant reported
15 Goldenhar Syndrome (Oculoauriculovertebral spectrum) Figure 99.8 Goldenhar syndrome. This 5-year-old boy has facial asymmetry and right microtia.Reference: Bailey’s Otolaryngology-Head & Neck Surgery
16 Jervell Lange-Nielsen Syndrome Autosomal recessive; one form linked to a potassium channel gene (KVLQT 1) on 11p15.Classic presentation:Deaf child who experiences syncopal episodes during periods of stress, exercise, frightProfound bilateral congenital SNHL (high frequencies worse)Heart disease: prolonged QT, large T waves, Stokes-Adams attacks (Cardiac syncope)Usually terminates fatally with sudden death; treated with ß-blockade
17 Noonan SyndromeOriginally thought to be a variant of Turner Syndrome- used to be referred to as “male version of Turner Syndrome”Autosomal DominantPTPN11 gene (12q24)Clinical Findings:Growth Development: 80% have short statureFacial Features:Triangular face, hypertelorism, down-slanting eyes, ptosis, strabismus (48%), amblyopia (33%), refractive errors (61%), low-set ears with thickened helices, high nasal bridge, short webbed neck.Otologic Features: progressive HF-SNHL in up to 50%Chest/Back Features: pectus carinatum/excavatum, scoliosisCardiac Features: pulm valve stenosis common, possibly any defectAbdominal Features: hepatosplenomegaly (25%)Genitourinary Features: renal anomalies (10%), undescended testes (50%)Skeletal Features: bleeding diasthesis,joint laxity (50%), radioulnar synostosis, cervical spine fusionSkin Findings: lymphedema, prominent pads fingers and toes (67%), follicular keratosis of face and extensor surfaces (14%)Neurologic Features: hypotonia, Sz disorder (13%)
18 Pierre-Robin Sequence Triad of:RetrognathiaGlossoptosisCleft palatePathology: due to retrognathia which prevents descent of the tongue into the oral cavity; prevents secondary palate fusionAssociated with a syndrome in 50-80% of cases, most commonly Stickler & VCF syndromes
19 Pierre-Robin Sequence Figure Robin sequence. This infant required a tracheostomy because of airway compromise from severe micrognathia.
20 Stickler SyndromeAutosomal dominant, mutation of COL2A1 gene on chromosome 12responsible for type II collagen geneCOL2A1: typically mild and not significantly progressive hearing lossCOL11A1: more severe hearing lossCOL11A2: non-ocular Stickler syndrome, hearing like COL11A1Small jaw with Robin sequence & cleft palateMyopia with retinal detachment & cataractsHypermobility & enlarged joints, early onset arthritis, occ. spondyloepiphyseal dysplasiaSNHL or mixed HL in 80%, educationally significant in 15%
21 Usher Syndrome Autosomal recessive, 10% of hereditary deafness Retinitis pigmentosa causing progressive visual loss.Patients born deaf secondary to atrophy of organ of Corti.Ataxia and vestibular dysfunction commonEye changes detected on electroretinography even before funduscopic changes identified; ophthalmology consult essential
22 Usher Syndrome Four main types: Type I: profound congenital deafness, RP onset by age 10, no vestibular response; 90% of UshersType II: moderate/severe congenital deafness, onset of RP in teens/twenties, normal or decreased vestibular response, 10% of all casesType III: progressive HL, RP begins in puberty, <1% of casesType IV: X-linked inheritance, similar to type II
23 Velocardiofacial Syndrome (Shprintzen Syndrome) Autosomal dominant, characterized by abnormal facies, VPI, CLP, and cardiac anomaliesHemizygous microdeletion of 22q11Almond shaped palpebral fissures, deficient nasal alae, tubuar nose with bulbous tip, small mouthLong face with vertical maxillary excess, malar flatness, mandibular retrusionPalatal clefting ranges from submucus clefting to overt wide cleft palate with hypernasalityCardiac anomalies in 80%, most commonly VSD; other anomalies include right sided aortic arch, tetralogy of Fallot, aortic valve diseaseMedial displacement of ICA’s present in up to 25% of patients
25 Waardenberg SyndromeDefined by the presence (type I) or absence (type II) of dystopia canthorum; SNHL occurs in 20% in Type I, 50% in Type IIAutosomal dominantType I gene locus PAX3 on chromosome 2Type II gene locus MITF (microphthalmia transcription factor) on chromosome 3 (20% of cases)Clinical findingsPigment abnormalities: white forelock, premature graying, vitiligo, heterochromia iridisCraniofacial abnormalities (dystopia canthorum, broad nasal root, synophrys)Unilateral or bilateral SNHLKlein-Waardenburg (Type III): features of WS1 plus blue eyes, hearing impairment, upper limb skeletal dysplasias, muscular hypotoniaWaardenburg-Shah (Type IV): phenotype similar to WS2 plus Hirschprung megacolon; AR
26 Waardenberg SyndromeType I: Dystopia canthorum present; this condition is 20 times more common than type II.Type II: Dystopia canthorum not present; hearing loss is more common in this type (50%) as well as pigmentary disorders.Type III: Klein-Waardenburg syndrome or pseudo-Waardenburg, no dystopia canthorum but with one-sided ptosis of the upper eyelid and upper limb anomalies.
27 Waardenberg SyndromeFigure Waardenburg syndrome. This mother and daughter have Waardenburg syndrome type I. Both have hearing loss and dystopia canthorum. The child also has heterochromia irides.
28 Neurofibromatosis 1 (Von Reklinghausen Disease) Diagnostic criteria includes 2 or more of the following:Six or more café au lait macules larger than 5 mm in the greatest diameter in prepubertal children and larger than 1.5 cm in postpubertal individualsTwo or more neurofibromas of any type or 1 plexiform neurofibromaMultiple freckles (Crowe sign) in the axillary or inguinal regionA distinctive osseous lesion, such as sphenoid dysplasia or thinning of long bone cortex, with or without pseudoarthrosisOptic gliomaTwo or more iris hamartomas (Lisch nodules) seen on slitlamp or biomicroscopy examinationA first-degree relative (parent, sibling, offspring) with same disease, as diagnosed by using the above criteria.
29 Neurofibromatosis 1 (Von Reklinghausen Disease) Mental retardation, learning disabilities, and speech defects are not uncommonAutosomal dominant. NF1 gene location is in the 17q11.2 region. Fresh mutations represent about 50% of cases
30 Neurofibromatosis 2Autosomal dominant, with 95% penetrance and linkage to 22q11-q13. The gene has been isolated, and encodes a protein named merlinDiagnostic criteria include the following:Bilateral acoustic neuroma seen with CT or MRI orA first-degree relative with the disease and either unilateral 8th nerve mass, or two of the following:neurofibromameningiomagliomaschwannomajuvenile posterior subcapsular lenticular opacity
31 Kartagener SyndromeAutosomal recessive inheritence. Autosomal dominant or X-linked inheritance has also been suggestedPansinusitis in childhood, absence of the frontal sinuses, and thick nasal rhinorrheaAnosmia and nasal polyps are frequent complications.Mastoid air cells are poorly developed.Otitis media as a result of eustachian tube dysfunction results in deafness, usually of the conductive typeRecurrent pneumonia and chronic cough are common.Situs inversus with gross defects in cardiac septation may occur. One-sixth of situs inversus cases have the syndromeImmobility of the sperm produces sterility in the males; affected females may have decreased fertility. The lack of dynein arms is the most common structural abnormality in the respiratory and fallopian cilia and the sperm tails
32 Sturge-Weber Syndrome (Encephelotrigeminal angiomatosis) Present at birth with seizure and large port-wine birthmark on side of faceCapillary malformation of the ophthalmic division of the trigeminal nerve.Associated with vascular malformations of the leptomeninges, leads to ischemic atrophy and cortical calcificationClinically causes seizures, focal neurologic deficits, developmental delay
33 Pfeiffer’s syndromeSimilar to Apert Syndrome but have digital broadening rather than syndactyly
34 Harlequin Syndrome Severe ichthiosis syndrome Also known as Ichtheosis FetalisAutosomal RecessiveMutation in the lipid-transporter gene ABCA12 on chromosome 2.Ears: The pinnae may be small and rudimentary or absent.Nose: Nasal hypoplasia and eroded nasal alae may occur.
35 Moebius Syndrome (Congenital Facial Diplegia) Expressionless Faceabsence or underdevelopment of the 6th and 7th cranial nervesFirst symptom, present at birth, is an inability to suck.Other symptoms can include: feeding, swallowing, and choking problems; excessive drooling; crossed eyes; lack of facial expression;; eye sensitivity; motor delays; high or cleft palate; hearing problems; and speech difficulties.Small or absent brain stem nuclei that control the cranial nerves, as well as decreased numbers of muscle fibers, have been reported.Deformities of the tongue, jaw, and limbs, such as clubfoot and missing or webbed fingers, may also occur. As children get older, lack of facial expression and inability to smile become the dominant visible symptoms.Reference:
37 Maffucci syndrome Multiple cavernous hemangiomas Dyschondroplasia & shortening and deformity of involved bonesOccasional visceral vascular lesions25% incidence of chondrosarcoma
38 Kasabach-Merritt syndrome Up till recently associated with hemangioma; skin lesion with red/brown discoloration that suddenly enlarges into a violaceous plaqueCharacterized by platelet sequestration, ecchymosis, no female predominanceHistologic lesion: a tufted angioma or kaposiform hemangioendotheliomaManagement supportive; heparin contraindicated, use of blood products avoided because of increased trapping within lesion; anemia treated with PRBC’s
39 Melkersen-Rosenthal Syndrome (Chelitis Granulomatosa) Most cases of sporadic. Familial occurrences suggest an autosomal dominant transmissionRecurrent or persistent lip swelling, facial swelling, facial palsy and furrowed tongueSwelling of the lips is usually of sudden onset, unilateral, or bilateral. The upper lip is affected in most cases and may remain swollen permanently. This occurs in 75% of patients.Histologically the swollen tissues exhibit chronic granulomatous changes similar to sarcoidosis or tuberculosisAuditory and visual disturbances, swelling in the hands and chest, blepharospasm, epiphora, and megacolon may be seen.The disease begins in childhood or early adulthood.It is considered a local immune response and vasomotor disturbance affecting the vasa vasorum of the vessels supplying the facial nerve and neighboring structuresReference: Bailey’s Otolaryngology-Head & Neck Surgery
40 References/Acknowledgments Bailey’s Otolaryngology-Head & Neck SurgeryCumming’s Otolaryngology-Head & Neck SurgeryUniversity of Alberta Otolaryngology Notes