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Foreword:

The mere absence of one

symptom or clinical featurecannot exclude a Disease

entity since signs andsymptoms vary in every

individual



individual

Southwestern UniversityMHAM College of Medicine

CLINICO-PATHOLOGIC CASECONFERENCE

by: ACLB



General Data:

• Baby Boy T., Male neonate,Roman Catholic, Filipino,

from Looc, Salvacion, Lapu-lapu City. Delivered viaCesarean section secondaryto Encephalocele



Prenatal history:

• Mother is 36 years old, G2P1001• Blood type O Rh positive• Works in a Coffee shop• Prenatal care started at 4 months

AOG at VSMMC• Ultrasound (4 months AOG)- noted a

mass at the frontal area of the head.• Continued PNC with a private

Obstetrician



Prenatal history:

• Repeat Ultrasound at 7 months AOG-Enlarging mass was noted at thefrontal area of the head and cleft lip.



Natal history:

• Patient was delivered via Cesareansection secondary to Encephalocele

• Has good cry and good respiratoryeffort

• APGAR score: 8, 9• Ballard score: 39 weeks• Birth weight: 2,600 grams• AGA



Physical examination:

Anthropometricmeasurements

Interpretation byPercentile:

Head circumference:

31.5 cm

10p

Chest circumference:31 cmAbdominal girth: 29 cm

Body length: 48 cm 25p

Birth weight: 2.6 kg 10p




• Vital signs:

HR 150 bpm 147 +/- 30.5

RR 50 cpm 59 +/- 18.2

Temperature:37.5

36.5- 37.5(core)






CVS Distinct Heart sound, nomurmur

Abdomen Globular, Umbilical cord has 2Arteries & 1 vein, soft, noorganomegaly

Genitalia Grossly male, Testes down,

good rugae

Extremities No Gross deformity, CRT < 2seconds



The Salient Features



Salient Features:

• ANTENATAL HISTORY:- Mother is 36 years old- Ultrasound at 4 months AOG showed a

mass at the frontal area of the head- Repeat ultrasound at 7 months AOG-

showed an enlarging mass at thefrontal area of the head

- Cleft lip





Salient Features

Encephalocele- Occipital encephalocele is the most

common- 70 % of cases- Increased risk of developing

Hydrocephalus in any of the followingetiologies:Aqueduct stenosis,Chiari malformation,Dandy-Walker syndrome



Salient feature

• Meckel-Gruber syndrome is a rareautosomal recessive condition that ischaracterized by an occipital

encephalocele.• Anterior encephalocele is associated

with Trisomy 18 and Robert’s

syndrome • Encephaloceles can be an isolated

finding or part of multiple anomalies like

chromosomal abnormalities



Anterior encephalocele



Cranium bifidum



Salient feature

• Frontal encephalocele alwayscontain brain tissue and involvebridge of nose (60%) and nasalcavity (30%)



Conditions with AnteriorEncephalocele

• MULTIFACTORIAL INHERITANCESingle Mutant gene: -Roberts syndrome-Median-cleft face syndromeChromosomal abnormalities:

-Trisomy 13 and 18



Salient feature:

• CLEFT LIP and CLEFT PALATE-Are distinct entities closely related

embryologically, functionally, andgenetically

-The incidence of cleft lip with or withoutcleft palate is ≈1/750 white births

-the incidence of cleft palate alone is≈1/2,500 white births



Salient Feature: Cleft lip/ Cleft palate

-Possible causes include maternal drugexposure, a syndrome-malformationcomplex, or genetic factors

-It can appear sporadically or inherited ina dominant fashion- van der Woude syndrome

- Can be part of a Multiple anomalysyndrome or can be an Isolated case



Salient features:



Salient feature:Isolatedanomaly

Cleft lip, cleft palate or bothAtypical facial cleft

Sequence Robin sequence;Holoprosyncephaly sequence;

Frontonasal dysplasiaChromosomalabnormalities

Trisomy 13, 18, 21; othertrisomies

Monogenicsyndromes Autosomal dominant;autosomal recessive disorders;X-linked disorders

Association Multiple congenital anomaliesof unknown etiologies



Salient features:

• Widely spaced eyesHYPERTELORISM

- is an increased distance between theorbits of the face

- Can be an isolated finding, and in manycases may be normal for that individual.However, it may also be seen as part ofa group of defects



Salient Feature

Conditions with Hypertelorism:• Chromosomal (sex chromosome abnormalitiesinvolving extra X chromosomes, unusual trisomy’ssuch as trisomy 14 and 9, chromosome deletions,

etc.)• Skull dysplasias – craniosynostosis disorders

(Apert’s Syndrome, Crouzon’s Syndrome,Carpenter’s Syndrome, Pfeiffer Syndrome, andSaethre-Chotzen Syndrome)

• Median facial plane defects (anterior cephaloceleand median facial cleft syndrome)



Salient Feature:

• Mid-face tumors or growths (teratomas,gliomas, hemangiomas, mucoceles, etc.)

• Genetic Syndromes (such as Waardenburgsyndrome, Noonan Syndrome, RiegerSyndrome, Opitz Syndrome, etc.)

• Defects of the Brain (hydrocephalus,agenesis of the corpus callosum,

lissencephaly, megalencephaly, etc.)



Salient feature

• Right Palpebral fissure smaller than theLeft:

=Microphthalmia -usually associated with malformations

=In unilateral microphthalmia, the normal eye can have apparent abnormality

=can be due to teratogens or chromosomal abnormalities or inheritance



Salient feature:

• 4 Nostrils:• Polyrrhinia (Double nose) or

supernumenary nostrils ( accessorynostrils

• Usually associated with Genetic defect,chromosomal abnormalities,

pseudohypertelorism, or it can be anisolated case



Salient feature

• Developmentalanomalies of the noseencompass a diverse

group of conditions.



Salient feature

• LOW SET EARS



Salient Feature

• Rare conditions that can cause low-setand malformed ears include:

• Beckwith-Wiedemann syndrome• Potter syndrome• Rubinstein-Taybi syndrome• Smith-Lemli-Opitz syndrome• Treacher Collins syndrome• Trisomy 13

• Trisomy 18



Salient Feature

• SMALL PHARYNGEAL AREA-May occur as a result of Cleft Palate-Associated with nasal defects



Salient Feature

• DISTINCT HEART SOUND, NOMURMUR

-Does not signify Congenital Heart defectis absent in the Neonate



Salient Feature

• NO GROSS DEFORMITY ON THEEXTREMITIES

• GENITALIA GROSSLY MALE,TESTES DOWN, GOOD RUGAE



Salient Feature:

• APGAR: 8,9• BALLARD SCORE: 39 WEEKS• BIRTH WEIGHT: 2,600 GRAMS• APPROPRIATE FOR GESTATIONAL

AGE• HEAD CIRCUMFERENCE: 31.5

cm(10p)• BIRTHLENGTH : 48 cm (25p)



INQUIRIES

• Are there any physical deformities onthe head of his Parents? Is itnormocephalic, Large or small or

appropriate• Any Facial feature distinguishable from

the Parents?

• Any relative with congenital defect?• In the Antenatal history, Did the mother

incurred any illnesses?



Inquiries

• Was the mother exposed to Radiationin the first and second trimester?

• Any medications the mother is takingduring pregnancy?

• Did she use medications to abort thefetus?

NATAL History:• Was the Cesarean elective or

emergency?



Inquiries

• Is the fontanel open? Specially theAnterior fontanel?

• Is the Head Deformed or asymmetricalor Normocephalic?

ANCILLARY PROCEDURES• Was Babygram done?• CT scan?• MRI?• Cranial ultrasonography?



• Echocardiogram?• Chest Radiography?• Was Karyotyping done? Or requested?• What are the results of the above

mentioned procedures?



ALGORITHM of DIAGNOSIS





Impression

MEDIAN-CLEFT FACE

SYNDROME(FRONTONASAL DYSPLASIA)

to considerTRISOMY 13 (PATAU SYNDROME)



Median-Cleft face syndrome



Median-cleft face syndrome(FRONTONASAL DYSPLASIA)

• Rare condition in which the midfacedoes not develop normally

• Affects the head and face

ETIOLOGY

• Cause is not known but can besporadic or familial

FRONTONASAL DYSPLASIA



FRONTONASAL DYSPLASIAPATHOGENESIS • Anomalies explained by single

malformation – Nasal capsule fails to develop properly

causing disruption in the positioning in

the eyes and lack of formation of nasaltip

– Considered nonspecific developmentalfield defect

• Failure of two nasomedial processes tomerge in midline produces the rare truemidline cleft lip, cleft palate and

Hypertelorism.

CLINICAL FEATURES OF



CLINICAL FEATURES OFFRONTONASAL DYSPLASIA

Eyes HypertelorismLateral displacement of inner canthi

Nose Varies from notched broad nasal tip, dividednostrils with hypoplasia, absence of prolabiumand premaxilla with cleft lip

forehead Widown's peakDefect in midline frontal bone (craniumbifidum occultum)

Mouth Cleft lip and/or cleft palate

others Frontal cutaneous lipoma or lipoma of corpuscallosum, Agenesis of corpus collosum

Anterior basal encephalocele

Frontonasal Dysplasia (Median-cleft lip



Frontonasal Dysplasia (Median-cleft lipsyndrome



FRONTONASAL DYSPLASIA(MEDIAN-CLEFT FACE SYNDROME)

DIFFERENTIALDIAGNOSES



Trisomy 13 ( Patau syndrome)

• the fourth most common autosomaldisorder in humans

• prevalence of about 1/10,000 to 1/15,000live births

• is caused by the presence of an extracopy of chromosome 13

• Recurrence in future pregnancies is about1% in families where the mother is lessthan 35 years old

• It is most likely the age-specific risk for

the older mothers



TRISOMY 13

Pattern of malformation

orofacial cleft congenital heart

malformations – 80%microphthalmia Encephalocele

posterior polydactylyof the limbsholoprosencephaly

Rudolphs Pediatrics, 21th edition



Trisomy 13- CLINICAL FINDINGSNelson’s textbook of Pediatrics, 18 th edition

small abnormal skull;cerebral malformation,especially holoprosencephaly

Cleft lip often midline low-set malformedears

flexed fingers withpolydactyly

microphthalmia

ocular hypotelorism cardiac

malformations bulbous nose scalp defects

hypoplastic or absentribs

visceral and genitalanomalies





Trisomy 13



Trisomy 13



Trisomy 13A 37 2/7 week gestational age male

infant with Patau syndromedemonstrating alobarholoprosencephaly withcyclopia . A) Facial features includedsloping forehead with a proboscissuperior to a single central palpebral

fissure. B) Close-up of the fusedeyelids and proboscis showing asingle nostril



Trisomy 13

• The presence of holoprosencephalyis probably the single mostimportant finding that predicts

survival



TRISOMY 13 DIAGNOSIS

• CYTOGENETIC STUDIES -chorionic villous sampling (10-13 weeks'

gestation) or amniocentesis (15 weeks'

gestation or later)

fluorescent in-situ hybridization (FISH)

i 3 G OS S



Trisomy 13 DIAGNOSIS

• BLOOD CHEMISTRY -maternal serum alpha fetoprotein

(MSAFP),

-human chorionic gonadotropin (hCG),-Unconjugated estriol,-inhibin





• IMAGING STUDIES WHILE IN UTERO

SERIAL ULTRASONOGRAPHY-determination of any Gross structuralabnormalities of the Fetus-Nuchal transluscency

T i 13 Di i



Trisomy 13- Diagnosis

• KARYOTYPING- Determine the number of chromosomes- Determine any structural changes in the

chromosomesNormal result:Females: 44 autosomes & 2 sex chromosomes

( 46, XX)Males: 44 autosomes & 2 sex chromosomes( 46, XY)

Patau syndrome: (47, XX,+13)

T i 13 Di i



Trisomy 13 Diagnosis

• Cranial ultrasound• Magnetic Resonance Imaging• CT-scan• Baby gram• Chest X-ray

B i f i l i



Basis for inclusion

• Pattern of inheritance• Gross facial features- Hypertelorism- Midline cleft lip and cleft palate- Low set ears- Abnormal nasal structure- encephalocele

B i f E l i



Basis for Exclusion

• Pattern of inheritance• Absence of Congenital heat malformation

based on PE

• Absent Lower limb defect• Absence of holoprosyncephaly• Appropriate for Gestational Age

• No microcephaly

CRANIOFRONTOFACIAL DYSPLASIA



CRANIOFRONTOFACIAL DYSPLASIA

• A.K.A.COHEN SYNDROME-Usually an Inherited

X- linked dominantdisorder-Females are more

affected and moreSevere than Males-Birth weight and

length are normal

C i f t l d l i (C h )



Craniofrontonasal dysplasia (Cohen)

CLINICAL FEATURES:• Coronal craniosynostosis• Brachecephaly• Frontal bossing• Profound ocular hypertelorism• Telecanthus• Coloboma• Syndactyly of the Phalanges and

Toes

C i f t l d l i



Craniofrontonasal dysplasia

• Broad nasal tip or Bifid nose• Camptodactyly - presence of

contracture deformity of the proximal

interphalangeal joints• Pectus excavatum• Splitting and Brittle nails• Psychomotor developmental problems

C i f t l d l i




Camptodactyly

Craniofrontonasal d splasia




Brachycephaly , alsoknown as flat headsyndrome , is a typeof cephalic disorder.This occurs whenthe coronalsuture fuses

prematurely, causing ashortened front-to-backdiameter of the skull



Basis for inclusion



Basis for inclusion

• Pattern of inheritance• Ocular hypertelorism• Nasal deformity• Appropriate for Gestational age

Basis for Exclusion



Basis for Exclusion

• Pattern of Inheritance• Absent cleft lip and palate• No encephalocele• Absence of limb anomaly

Roberts syndrome



Roberts syndrome

• A.K.A.= Hypomelia-Hypotrichosis-FacialHemangioma syndrome;

PseudothalidomideSyndrome

• Autosomal recessive

disorder

Roberts syndrome



Roberts syndrome

• Rare genetic disordercharacterized by growth delaysbefore and after birth (pre- and

postnatal growth deficiency);malformations of the arms andlegs (limbs ); distinctive

abnormalities of the skull and facial (craniofacial) region

Roberts syndrome Clinical Features



Roberts syndrome- Clinical Features

• Bilateral SymmetricTetraphocomelia

• Prenatal growth retardation• Cleft lip/or Cleft palate

• Microbrachycephaly• Ocular Hypertelorism• Exophthalmos• Hypoplastic ala nasae with

beaked nose• Low set , malformed ear

• Ence halocele

b d



Roberts syndrome- Diagnosis

CLINICAL DIAGNOSIS:• Prenatal Growth Retardation - low

birth length and weight that can range

from mild to severe• Limb Malformations - bilateral

symmetric tetraphocomelia,

oligodactyly, thumb aplasia, syndactyly,clinodactyly, and elbow and kneeflexion contractures

Roberts syndrome Clinical dx



Roberts syndrome- Clinical dx

• Craniofacial Abnormalities - bilateralcleft lip andpalate, micrognathia, hypertelorism, ex

ophthalmos, down-slanting palpebralfissures, malar hypoplasia, hypoplasticnasal alae, and ear malformations

Roberts syndrome Diagnosis



Roberts syndrome- Diagnosis

• Laboratory DiagnosisCytogenetic Testing- Premature centromere separation

(PCS) and is the most likely pathogenicmechanism for Roberts syndrome.Imaging studies in-utero

-Supportive

Basis for inclusion



Basis for inclusion

• Pattern of Inheritance• Presence of midline cleft lip and cleft

palate

• Ocular hypetelorism• Anterior encephalocele• Nasal structural defect

Basis for Exclusion:



Basis for Exclusion:

• No phocomelia or Limb anomalies• No growth restriction in utero• No growth restriction based on

Anthropometric measurements• No exophthalmos



Thank very much!