CLEFT LIP & palate

Types MALFORMATION

SYNDROMEDown syndrome (trisomy 21)Extra copy of Chromosome 21 (95%)Growth retardationVarying degrees of mental retardationCraniofacial abnormalitiesUpward slanting eyesEpicanthal foldsFlattened faciesSmall earsCardiac defectsHypotoniaMost of the time due to meiotic nondisjunction risk in women > 35 (1 in 1000 1 in 400)

Trisomy 18 Mental retardationCongenital heart defectsLow set earsFlexion of fingers & handsMicrognathiaRenal anomaliesSyndactylyMalformations of the skeletal systemInfants usually die by age 2 monthsIncidence is 1 in 5000

Trisomy 13Mental retardationHoloprosencephalyCongenital heart defectsDeafnessCleft lip & palateEye defectsMicrophthalmiaAnophthalmiaColobomaMost infants die by age 3 monthsIncidence 1 in 15,000

Klinefelter SyndromeFound only in males (47, XXY most common)Usually detected at pubertyI in 500 malesNondisjunction of XX homologuesSterilityTesticular atrophyHyalinization of seminiferous tubulesGynecomastiaMaybe some mental impairment with # of X chromosomes (e.g. 48, XXXY)

Turner SyndromeFound in women with unmistakably female appearanceAbsence of ovaries (gonadal dysgenesis)Short statureWebbed neck (frequently)Lymphedema of the extremitiesSkeletal deformitiesBroad chest with widely spaced nipplesUsually (45, X) missing one X chromosome

Angelmans vs. Prader-Willi Syndrome

CLEFT LIP & palateCleft lip and palatefacial and oral malformations that occur very early in pregnancy, while the baby is developing inside the mother

6th to 10th week of pregnancy, the bones and tissues of a baby's upper jaw, nose, and mouth normally come together (fuse) to form the roof of the mouth and the upper lip. If the tissue in the developing mouth and the palate don't fuse together, a baby could be born with a cleft lip or cleft palate, or both.Cleft Lipphysical split or separation of the two sides of the upper lip and appears as a narrow opening or gap in the skin of the upper lipoften extends beyond the base of the nose and includes the bones of the upper jaw and/or upper gumCleft Palatesplit or opening in the roof of the mouthcan involve the hard palate (the bony front portion of the roof of the mouth), and/or the soft palate (the soft back portion of the roof of the mouth)

Unilateral cleft lip the gap is only on one side of the lip under either the left or right nostril and might extend into the nose. The noses of babies with unilateral cleft lip may look tilted and flat on one side.

bilateral cleft lip have a gap on both sides of the lip, and they may have a deep split in the lip that extends into both nostrils. This may cause the nose to look broader and shorter than normal.

In most cases, the cleft occurs only in the upper lip and doesn't affect the lower lip.CausesGenes inherited from the parents. Exposure to certain substances during pregnancy. -SmokingWomen who smoke during pregnancy are more likely to have a baby with an orofacial cleft than women who do not smoke.-Alcohol Drinking-Taking certain medicinesDiabetesWomen with diabetes diagnosed before pregnancy have been shown to be an increased risk of having a child with a cleft lip with or without cleft palateNot enough folic acidINCIDENCEIt is more common in developing countries than in developed countries.a) Highest in Asian populations b) Intermediate in Caucasian populations c) Lowest in African populations

National statistics:1-2/1,000 live births with cleft lip being more common than cleft palate Computations for annual load:Birth Rate = 27.85 births/1,000population Population = 81,159,644Birth/annum = 2,260,296New CLP cases/annum = 2,260Treatment of cleft lip and palateSurgery-cleft lip repair is done when the child is 6 to 12 weeks old-cleft palate repair is done between 9 mo. and 1 yr. old

Hydrocele

collection of fluid which gradually develops around the testicle, producing a swelling in the scrotum between the visceral and parietal areas of tunica vaginalisCausesIn infants, usually due to the following:Incomplete closure of the processus vaginalis from the peritoneumResidual peritoneal fluid that has yet to be reabsorbed after processus closure

In older boys and men may be idiopathic but usually due to abnormal absorption or secretion secondary to another pathologic process such as:TraumaIschemiaInfection (sexually transmitted or other)Testicular tumorIncreased intra-abdominal pressureINCIDENCE10 to 60/1,000 newborn full-term boys and 10/1,000 adult men

More common in infancy but can occur at any ageTREATMENTHydrocoelectomy-remove the fluid which has collected around the testicle and prevent it forming again-usually carried out under a general anesthetic (when you are put to sleep) and may take around 20 to 30 minutes

PROCEDURE:1. very small cut in the scrotum or lower tummy (abdominal) wall. 2. The fluid is then drained from around the testicle (testis). 3.The passage between the abdomen and the scrotum will also be sealed off so the fluid cannot re-form in the future. Preventive MeasuresMinimize potential for trauma to scrotum with use of protective devices in high-risk situations

Minimize potential for transmission of sexually transmitted diseases through patient education regarding prevention

Patients with family history of Ehlers-Danlos syndrome can be alerted to watch for signs of hydrocele formationCryptorchidismundescended testicle refers to a testicle (testis) that has not moved into the scrotum before a baby is born

During pregnancy a baby's testicles form in his abdomen, before gradually descending into the scrotum, usually around the 8th month.

2%-4% of male infantsPalpable undescended testicles - the testicle(s) can be felt during a physical examination. Accounts for about 80% of cases.

Unpalpable undescended testicles - the testicle(s) can't be felt during a physical examination. There are three main types:

Abdominal or intra-abdominal - 40% Inguinal - 40%Atrophic or absent -20%Diagnostic TestUltrasound scan.MRI (magnetic resonance imaging) scan Open surgery

Orchiopexy can be carried out when the boy is age between 6 and 18 months old.ENVIRONMETALInfectious AgentsRubella (German Measles)Malformations of the eyeCataract (6th week) MicrophthalmiaMalformations of the ear (9th week)Congenital deafnessDue to destruction of cochleaMalformations of the heart (5th -10th week)Patent ductus arteriosisAtrial septal defectsVentricular septal defectsInfectious Agents (cont.)Rubella (German measles) May be responsible for some brain abnormalitiesMental retardationIntrauterine growth retardationMyocardial damageVascular abnormalitesIncidence 47%- during 1st four weeks22% - 5th 8th weeks13% - 9th 16th week

Infectious Agents (cont.)Rubella (cont.)Lab tests permit detection of virusAntibody levels can be determinedIn one study 85 % of women tested were immune (n = 600)Virus infects fetus via the placentaInfection of the child may persist after birth for a number of yearsInfection can be transmitted to hospital personnelVaccines are considered safe & effectiveInfectious Agents (cont.)CytomegalovirusDisease is often fatal early onMalformationsMicrocephalyCerebral calcificationsBlindnessChorioretinitisKernicterus (a form of jaundice)multiple petechiae of skinHepatosplenomegalyMother asymptomaticInfectious Agents (cont.)Herpes Simplex VirusIntrauterine infection of fetus occasionally occursUsually infection is transmitted close to time of deliveryAbnormalities (rare)MicrocephalyMicrophthalmosRetinal dysplasiaHepatosplenomegalyMental retardationUsually child infected by mother at birthInflammatory reactions during first few weeksInfectious Agents (cont.)Varicella (chickenpox)Congenital anomalies 20% incidence following infection in 1st trimesterLimb hypoplasiaMental retardationMuscle atrophyHIV/AIDSMicrocephalyGrowth retardationAbnormal facies (expression or appearance of the face)Infectious Agents (cont.)

ToxoplamosisProtozoa parasite (Toxoplama gondii)SourcesPoorly cooked meatDomestic animals (cats)Contaminated soil with fecesSyphilisCongenital deafnessMental retardationDiffuse fibrosis of organs (eg. liver & lungs)In general most infections are pyrogenicHyperthemia can be teratogenicFeverHot tubs & Saunas 39RadiationTeratogenic effect of ionizing radiation well establishedMicrocephalySkull defectsSpina bifidaBlindness cleft palateExtremity defectsDirect effects on fetus or indirect effects on germ cellsMay effect succeeding generationsAvoid X-raying pregnant womenRadiationIonizing radiation kills rapidly proliferating cells, producing any type of birth defect depending upon dose and stage of development. Ex. Atomic bomb on Hiroshima and Nagasaki. Exposure of the pregnant woman to a large dose of x- ray can lead to microcephaly, spina bifida or cleft palate.

Chemical agents/DrugsThere are many dangerous drugs, if have given to the pregnant female, can produce congenital anomalies. Ex.: Thalidomide (antinauseant sleeping pills) produce limb defects (phocomelia) and heart malformations. Diphenylhydantoin produce facial defects and mental retardation.Tetracycline (bone and teeth anomalies)Aspirin may cause harm in large doses.Cocaine cause birth defect possibly to its effect as a vasoconstrictor that cause hypoxia.Alcohol cause fetal alcohol syndrome.

DrugsThalidomideAntinauseant & sleeping pillFound to cause amelia & meromeliaTotal or partial absence of the extremitiesIntestinal atresiaCardiac abnormalitiesMany women had taken thalidomide early in pregnancy (in Germany in 1961) Drugs (cont.)AminopterinAntagonist of Folic AcidAntineoplastic agent which inhibits mitosisDefectsAnencephalyMeningoceleHydrocephalusCleft lip & palateDrugs (cont.)Anticonvulsants (to treat epilepsy)Diphenylhydantoin (phenytoin)Craniofacial defectsNail & digital hypoplasiaGrowth abnormalitiesMental deficiencyThe above pattern is know as fetal hydantoin syndromeValproic acidNeural tube defectsHeart defectsCraniofacial & limb anomaliesDrugs (cont.)Trimethadione (syndrome)Malformed earsCleft palateCardiac defectsUrogenital anomaliesSkeletal anomalies

Drugs (cont.)Antipsychotic drugs (major tranquilizers) Phenothiazine & lithiumSuspected teratogenic agentsAntianxiety drugs (minor tranquilizers)Meprobamate, chlordiazepoxide, Severe anomalies in 11-12% of offspring where mothers were treated with the above compared to 2.6% of controlsdiazepam (valium)Fourfold in cleft lip with or without cleft palateDrugs (cont.)AnticoagulantsWarfarin (A.K.A cumadin or cumarol)TeratogenicHypoplasia of nasal cartilageChondrodysplasiaCentral nervous system defectsMental retardationAtrophy of the optic nervesAntihypertensive agents angiotensin converting enzyme (ACE) inhibitorGrowth dysfunction, renal dysfunction, oliogohydramnios, fetal death Drugs (cont)PropylthiouracilGoiterMental retardationPotassium iodideGoiterMental retardationStreptomycindeafnessSulfonamideskernicterus

Imipramine (antidepr.)Limb deformatiesTetracyclinesBone & tooth anomaliesAmphetaminesOral cleftsCV abnormalitiesQuinineDeafnessAspirinPotentially harmful in large dosesDrugs (cont.)Isotretinoin (13-cis-retinoic acid) Analogue of vitamin ADrug is prescribed for treatment of cystic acne & other chronic dermatosesHighly tertogenicReduced & abnormal ear developmentFlat nasal bridgeCleft palateHydrocephalyNeural tube defectsHeart anomaliesRecreational drugsPCP angel dustPossible malformations & behavioral disturbancesCocaine-vasoconstrictor hypoxiaSpontaneous abortionGrowth retardationMicrocephalyBehavioral problemsUrogenital anomaliesgastroschisis

AlcoholRelationship between alcohol consumption & congenital abnormalitiesFetal alcohol syndromeCraniofacial abnormalitiesShort palpebral fissuresHypoplasia of the maxillaLimb deformitiesAltered joint mobility & positionCardiovascular defectsVentricular septal abnormalitesMental retardationGrowth deficiency

Cigarette Smokinglinked to an increased risk for orofacial clefts (cleft lip and cleft palate)contributes to intrauterine growth retardation and premature delivery.HormonesAndrogenic AgentsSynthetic progestins were used frequently to prevent abortionEthisterone & norethisteroneHave considerable androgenic activityMasculinization of female genitaliaDiethylstilbesterolCommonly used in the 1940s & 1950s to prevent abortion; in 1971 determined that DES caused increased incidence of vaginal & cervical cancer in women who had been exposed to DES in uteroIn addition high % suffered from reproductive dysfunctionOral ContraceptivesLow teratogenic potential, discontinue if pregnancy suspectedCortisone-cleft palate in mice (not humans)Maternal DiseaseDisturbances in CHO metabolism (diabetic mothers)High incidence of stillbirth, neonatal deathsAbnormally large infantsCongenital malformations risk 3-4XCardiac, Skeletal, CNS AnomaliesCaudal dysgensisPartial or complete agenesis of sacral vertebrae in conjuction with hindlimb hypoplasiaHypoglycemic episodes teratogenicOral hypoglycemic agents maybe teratogenicMaternal Disease (cont.)Phenylketonuria (PKU)Enzyme phenylalanine hydroxylase is deficient phenylalanine (PA) concentrationsMental retardationMicrocephalyRisk can be with low PA dietHypoxiaAssociated with congenital malformations in a great variety of experimental animalsIn humans Maybe smaller babies e.g. offspring at high altitudeINCEDENCE

INCIDENCE

Philippine Birth Defect Registry ProjectDepartment of Health and the Institute of Human Genetics of the US National Institutes of Health (NIH)

February 1999 with 79 hospitals nationwide participating. For 1999- 2000, 191 576 deliveries, 6.3% of the annual births in the country.A total of 1240 cases of birth defects have so far been tallied, the top12 of which include: multiple congenital anomalies, congenital malformations of the tongue, mouth and pharynx(e.g., ankyloglossia), cleft lip and palate, Down syndrome, congenital deformities of the feet (e.g., talipes equinovarus), other congenital malformations of the face and neck(e.g., preauricular skin tags), anencephaly and similar neural tube defects, congenital malformations of the musculoskeletal system notelsewhere classified (e.g., diaphragmatic hernia, gastroschisis), hypospadias,35Global registry and database on craniofacial anomalies congenital hydrocephalus, polydactyly and syndactyly, and cleft lip only.

Philippine General Hospital (1996-2000)6742 cases with diagnoses of birth defects. The top 10 were: congenital malformation of the heart, unspecified, Hirschsprungs Disease, congenital absence, atresia, and stenosis of anus without fistula, unspecified CLP, bilateral, congenital hydrocephalus, unspecified, cleft lip and palate, CL and multiple congenital malformations, not elsewhereclassified, patent ductus arteriosus,36 spina bifida, unspecified, congenital cataract,MANAGEMENT

PRENATAL DIAGNOSISMethods of prenatal diagnosis are divided into invasive and non-invasive techniques.Technique Time Disorders diagnosed (in weeks)A. Non-invasive:Maternal serum screen:Alpha feto protein (AFP) 16 Neural tube defects (NTD)Triple test 16 Down syndromeUltrasound 18 Structural defects in many organs as CNS, heart, kidney, and limbs.

B. Invasive:- Amniocentesis 14-16 Chromosomal and metabolic abnormalities, and DNA analysis.- Chorionic villus sampling 10-12 As amniocentesis.- Fetal blood sample near term As amniocentesis + blood disorders.Technique of amniocentesis

Technique of CVS

U/S showing polydactyly

U/S showing micrognathia

U/S showing Umibilical hernia (associated with Trisomy 18 in 50% of cases)Fetal therapyThe fetus during intrauterine life can receive treatment such as:1- Fetal transfusion (administration of blood transfusion to the anemic fetus in thalassemia). 2- Medical treatment of thyroid dysfunction or congenital adrenal hyperplasia of the fetus.3- Fetal surgery: is possible due to advanced ultrasound and surgical procedures eg: repair of hernia of the fetus or in case of hydrocphalus.4- Stem cell transplantation and gene therapy: it is possible to transplant stem cells before 18 weeks of gestation of the fetus without rejection because the immunocompetence of the fetus doesnt develop yet.