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Dysmorphology CHO NICU Lecture Prepared by PJ 12-16-11 Syndromes to Know • • • • • • Trisomy 21,18, 13 Turner’s and Kleinfelters diGeorge/VCF VACTERL Noonan’s Williams Orbital distance Hypotelorism • • • • Holoprosencephaly maternal PKU trisomy 13 Williams- neurodevelopmental d/o, elfin facies, overly cheerful Hypertelorism • • • • • • Apert cardio-facio-cutaneous coffin lowry- craniofacial (head and facial) and skeletal abnormalities, mental retardation, short stature, and hypotonia deletion 4p, 4q, 9p, 11q, 13q DiGeorge escobar syndrome- Escobar syndrome is a form of arthrogryposis multiplex congenita and features joint contractures, pterygia, and respiratory distress • • • • noonan syndrome trisomy 8, 13 XXXX CHARGE association Palpebral length Short palpebral fissure • • • • • DiGeorge Fetal alcohol syndrome maternal PKU effects trisomy 18 Williams syndrome Palpebral slant Slanted palpebral fissures • • • • • • • • • • Apert cardio-facio-cutaneous syndrome cat-eye syndrome (multiple other anomalies present) coffin-lowry syndrome deletion of 5p, 9p, 3q, 10q, 15q noonan syndrome trisomy 9 mosaic S XXXX, XXXXX, XXXXY prader willi trisomy 13, 18 Epicanthal fold Epicanthal folds • • • • • • • • • • • • • • • Deletion 3p, 4p, 5p, 9p, 11q, 13q, 18p down sydrome escobar syndrome duplication 9p fetal valproate fragile x hurler syndrome hypomelanosis of Ito- hypopigmented whirls along Blashko’s lines and skeletal anomalies maternal PKU noonan syndrome william syndrome x-linked alpha thal/MR XO XXXX XXXXX XXXXY Micrognathia • • • • • • • • • • • Pierre Robin Sequence Fetal alcohol syndrome Connective tissue: Marshall, Stickler, Marfan, Ehler Danlos Velocardiofacial, DiGeorge’s Treacher Collins syndrome Trisomy 13, 18 Turner syndrome Noonan syndrome Smith-Lemli-Opitz syndrome (inborn error of cholesterol metabolism) Russell-Silver syndrome (also downward turned in mouth) Cri du chat syndrome Pierre-Robin • • • • • Robin sequence — micrognathia + glossoptosis + U-shaped cleft palate Sequence from hypoplasia of mandible > posterior displacement of tongue, prevenTS palatal closure Associated with GERD, conductive hearing loss Upper airway obstruction in neonatal period – prone positioning – gavage feeding – nasal trumpet can help by bypassing obstruction at base of tongue – More invasivemeasures (trach, surg) if persistent resp difficulty. Delay closure of palatal defect to avoid worsening upper airway obstruction The tongue • • Glossoptosis - downward displacement/retraction of tongue(normal sized tongue) – Pierre Robin Sequence – Down Syndrome Macroglossia: Enlargement of the tongue – drooling, speech impairment, difficulty eating, stridor, airway obstruction – Beckwith Wiedemann: macrosomia, macroglossia, and abdominal wall defects – Hypothyroid – Mucopolysaccharidoses (progressive) – Down syndrome (papillary and fissured) Ankyloglossia • breastfeeding difficulty – – – • • • poor latch maternal nipple pain FTT difficulty with speech lactation consultant Frenotomy/Frenuloplasty – – ? Timing indications: Br feeding difficulty, articulation problems, psychologic, periodontal disease Cleft lip/cleft palate • • • • Cleft lip is more common in males, cleft palate in females. Nonsyndromic cleft lip and/or palate: incidence 1:1000 60% association with other anomalies or a syndrome Environmental Causes – – – • Chromosomal Causes – – – • Trisomies 13 and 18 (CL/CP) Wolf-Hirschhorn or 4p− syndrome (CL/CP) Shprintzen or 22q11.2 deletion syndrome (CP) Single-gene disorders – – – • Maternal seizures, anticonvulsant usage (CL/CP or CP) Fetal alcohol syndrome (CP) Amniotic band syndrome (CL/CP) Treacher Collins syndrome, AD (CP) Stickler syndrome, AD (CP—particularly Pierre-Robin) Smith-Lemli-Opitz, AR (CP) HIGH ARCHED PALATE: associated with Noonan, Turners, 22q11 syndromes, Marfan’s Lip-philtrum • Score smoothness of philtrum and thinness of upper lip independently – • Scores of 4 or 5 are consistent with FAS. prominent, long filtrum - Williams (distinctive, "elfin”features, low nasal bridge, cheerful demeanor, strong language skills, DD, cardiac) Malformations of the External Ear Size of the auricle •Microtia (small ear) •Macrotia (large ear) •Anotia (absent ear) Shape of the ear •Cup-shaped •Lop-ear •Dysplastic •Elfin ear (pointed) •Lobe malformations Auricular fistulas Auricular appendages/tags External acoustic meatus •Atresia •Duplication •Septation Position of the ear •Melotia (ear on cheek- lack aural ascent) •Low set ears •Synotia (ears are very close to each other in the midline) Normal ear anatomy >3cm in full term neonate Abnormal Size Microtia -> Anotia Grade I: Almost complete development of the external ear with identifiable structures and a small but present external ear canal I II Grade II: A partially developed ear (usually the top portion is underdeveloped) with a closed off or stenotic external ear canal producing a conductive hearing loss. Grade III: Absence of the external ear with a small peanut-like structure; absence of the external ear canal. Grade IV: Absence of the total ear or anotia. Hearing eval, ENT referral, surgery usually at 4-6 yo •In utero exposures: isoretinoin, thalidomide, FAS, maternal diabetes, Cell cept •Goldenhar syndrome: unilateral microtia, small malformed mandible •Treacher-Collins syndrome: downward slanting eyes, small jaw, drooping lower eyelid, malformed or absent ears •Trisomy 18 •Trisomy 21 •Rubella and intrauterine infections III IV Macrotia (length >97% on curve) •Marfan syndrome •Fragile X-syndrome •Oligohydramnios (Potter syndrome) •Several syndromes: Cerebro-oculo-facial-skeletal syndrome, Weaver, Lamotte, Nance-Horan, PallisterKillian, Melnick-Needles, Langer Giedion Abnormal Shape Pointed ear Cup shaped ear Lop ear Auricular Cleft Dysplastic Ear Can be associated with chromosomal abnormalities: diastrophic dysplasia, antley bixler syndrome, trisomy 1315, ancephaly, Treacher Collins Abnormal Position of Ear Low Set Ears •Low set ear will fall below line drawn outer canthus of the eye straight back to the occiput •Normal set will cross or touch the same line •Noonan syndrome, Pena Shokeir (Neurogenic arthrogryposis, pulmonary hypoplasia, hypertelorism , Trisomy 18, Down’s Syndrome, Turners, DiGeorge, Edwards Syndrome, Goldenhar with low-set malformed ears) Auricular appendage or tag •May have associated unilateral hearing loss •Can be removed in childhood for cosmetic purposes Aural Atresia •Absent or stenotic ear canal •Normal middle ears- at risk for AOM •At risk for middle ear cholesteatoma •Bilateral atresia requires early intervention with hearing aids •Surgery to correct atresia performed toward first decade of life Preauricular Pits •Five times the risk of the general population for permanent hearing impairment •Branchio-oto-renal syndrome (most common inherited syndrome causing hearing loss)- audiologic testing •Does not require surgery unless repeatedly infected or discharges squamous material •Incidence of renal anomalies with isolated pit does not significantly differ from that of general population •Screening for renal anomalies more important when other anomalies/ dysmorphic features present, family hx deafness, renal or auricular malformations, or mom with history of gestational DM Association with renal anomalies •Occur in several congenital syndromes: branchio-oto-renal syndrome, CHARGE, Townes-Brocks syndrome (Lop ears, imperforate anus, hypoplastic kidney, ventricular septal defect, limb anomalies with autosomal dominant inheritance), Nager, Miller, IFDM •External ear anomalies possibly with increased risk •Kugelman 2002 showed in study- similar prevalence of renal anomalies between babies with pits/tags and those without •Recommend renal ultrasound in children with ear anomaly accompanied by one of the following: other malformation/dysmorphic features, family histor of deafness/ear/kidney malformation, maternal history of gest DM. •Controversial whether or not to get RUS on child with isolated pit/cup ear http://sonoworld.com/fetus/page.aspx?id=205 Hand and Upper Limb Anomalies • Syndactyly – 1 in 2,000-3,000 – Simple (soft tissue only) to Complex (bone or nail fusion) – May be associated with other syndromes, esp craniofacial – May be due to amniotic bands – 10-40% familial Hand and Upper Limb Anomalies • Polydactyly – – – – 1 in 500-1,000 Often familial (30%) Side varies by race! May be associated with other syndromes • Chondroectodermal dysplasia • trisomy 21 • trisomy 13 Hand and Upper Limb Anomalies • Camptodactyly – PIP flexion deformity resulting in permanent flexion – Affects up to 1% of the population to some degree – Can worsen with growth spurts!!!! – May be associated with other syndromes, but uncommon Hand and Upper Limb Anomalies • Amniotic band syndrome – Bands originate from inner lining of amnion – Extremities may get tangled and constricted in the bands – May be associated with amniocentesis, trauma – Often no identified inciting event Hand and Upper Limb Anomalies • Absent radii – VACTERL association – Thrombocytopenia with Absent Radius Syndrome (TAR) – Fanconi Anemia Hand and Upper Limb Anomalies • Clinodactyly – Angulation at an IP joint – Runs in families – Associated with over 60 syndromes! – 35-80% half of pts with Trisomy 21 have clinodactyly Trisomy 18 Kristin Riley, MS IV Epidemiology • Incidence of 0.3 per 100 newborn babies • 3:1 male to female ratio Etiology • Trisomy for all or a large part of the 18th chromosome – majority have full trisomy 18 • most die within fetal life • recurrence rate < 1% – mosaicism for an additional chromosome 18 – partial trisomy 18 Pre-Natal Screen • 1st trimester screen: – low beta-hCG – low PAPP-A – increased NT measurement – ~ 90% of trisomy 18 pregnancies can be identified with < 1% false positive rate using first trimester screening • 2nd trimester screen: – low levels of AFP, uE3, and beta-hCG Integrated Screen Additional Analyses • CVS at 10-12 weeks gestation • Amniocentesis at 15-20 weeks gestation Key Features Clinical Findings in > 50% of patients • Pre-Natal: – – – – Polyhydramnios Altered gestational timing Small placenta Single umbilical artery • General Exam: – – – – – Feeble fetal activity Weak cry Hypoplasia of skeletal muscle Hypertonicity Diminished response to sound Clinical Findings in > 50% patients • Craniofacial: – – – – – – – Prominent occiput Narrow bifrontal diameter Low-set auricles Short palpebral features Small oral opening Narrow palatal arch Micrognathia Clinical Findings in > 50% of patients • Hands: – Clenched hand, overlapping index finger over third finger and overlapping fifth finger over fourth – Absence of distal crease on fifth finger with or without distal creases on third and fourth fingers – Hypoplasia of nails especially on fifth finger and toes – Short hallux Clinical Findings in > 50% of patients • Thorax: – Short sternum with reduced # of ossification centers – Small nipples • Abdomen: – Inguinal or abdominal wall hernia Clinical Findings in > 50% patients • • • • Hips: Limited hip abduction GU: Male cryptochordism Skin: Mild hirsutism of forehead and back Cardiac: – – – – VSD ASD Auricular septal defect PDA Clinical Findings in 10-50% of patients • Craniofacial: Wide fontanels, microcephaly, hypoplasia of orbital ridges, inner epicanthal folds, ptosis of eyelid, cornial opacity, cleft lip or cleft palate • Hands and feet: Ulnar deviation of hand, hypoplastic or absent thumb, simian crease, equinovarus, rocker-bottom feet (prominent calcaneus), syndactyly of second and third toes Clinical Findings in 10-50% of patients • • • • • • • Thorax: Wide-spaced nipples Genitalia: Hypoplasia of labia majora with prominent clitoris Anus: Malposed or funnel-shaped Cardiac: Bicuspid aortic or pulmonic valves Lung: Malsegmentation Diaphragm: Muscle hypoplasia Abdomen: Meckels diverticulum, heterotopic pancreatic and or splenic tissue, omphalocele • Renal: Horsehoe defect, ectopic kidney, hydronephrosis, polycystic kidney Clinical Findings in < 10% of patients • CNS: facial palsy, paucity of myelination, defect of corpus collosum, hydrocephalus, meningomyelocele • Craniofacial: Wormian cranial bones, shallow elongated sella turcica, slanted palpebral features, hypertelorism, cataract, micropthalmos, choanal atresia • Hands: Syndactyly of 3rd and 4th fingers, polydactyly Clinical Findings in < 10% of patients • Genitalia: M: hypospadias; F: bifid uterus or ovarian hyperplasia • CV: Anomalous coronary a., transposition, TOF, coarctation of aorta, dextrocardia, aberrant subclavian a., intimal proliferation in arteries • Abdominal: Pyloric stenosis, extrahepatic biliary atresia, gallstones, hypoplastic GB • Renal: Hydronephrosis, polycystic kidney disease, Wilms tumor • Endocrine: Thyroid or adrenal hypoplasia Natural History in Neonatal Period • • • • • Apneic periods Poor suck which may necessitate NG tube 50% die within the first week Median survival is 14.5 days Only 5-10% survive to the first year of life – some have verbal communication and interact socially Our Patient • Ex 37 2/7 wk M infant born by C/S after fetal decels noted on tracing transferred to CHO from Alta Bates due to esophageal atresia with likely TEF and probable Trisomy 18. PN hx also + for IUGR and polyhydramnios. Hospital Course FEN/GI: UAC; UVC; TEF and suspected esophageal atresia (not commonly associated with Trisomy 18); NPO; NG RESP: CPAP CV: Echo: fenestrated ASD vs. PFO, VSD< systemic RV pressure ID: Ampicillin and Gentamicin for 48 hours with a negative blood culture GU: Undescended testes Renal: RUS: Horseshoe kidney with right pelviectasis, soft tissue pelvic mass present HCM: No hep B at birth, received vitamin K and erythromycin eye ointment GENETICS: karyotype Trisomy 18, genetics consulted Neuro: HUS: agenesis of the corpus callosum and dysplastic frontal lobes Phototherapy Physical Exam • GENERAL: Desats during exam to mid 80’s. Pink, appears uncomfortable with furrowed brows. • HEENT: Low-set ears, micrognathia. • RESP: Coarse breath sounds, transmitted sounds from NCPAP bilaterally. Subcostal retractions. • CV: Harsh II/VI holosystolic murmur. • ABD: Abdomen soft, non-distended. • GU: Undescended testes bilaterally. • EXT: Hands clenched in fists with overlapping fingers. Arachnodactaly, rocker-bottom feet. References • Jones, D. Smith’s Recognizable Patterns of Human Malformation. Sixth Ed. • Nelson Textbook of Pediatrics, 19th Ed. • UptoDate • NICU Manual, Children’s Hospital Oakland