What Else to Look for in a Child Born With

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What Else To Look for In A Child Born with

A Cleft of the Lip and /or Palate

HERMINE M. PASHAYAN, M.D. Boston, Massachusetts 02111

The majority of cases of cleft lip and/or palate fall into the category of multifactorial inheritance. Diagnosis is simple and guidelines giving estimates of the risk of recurrence for various situations are available. A few patients with cleft of the lip and/or palate have other structural abnormalities. Accurate diagnosis to outline treatment, predict prognosis and give genetic counseling in this latter group may be a problem for the clinician. A guideline to help make a diagnosis is presented in a set of 10 tables.

Clinicians and genetic counselors are aware and/or cleft palate as one manifestation. The of the fact that the great majority of patients accurate diagnosis in these cases depends on that present with an isolated cleft of the lip the clinicians knowledge of such syndromes. and/or palate fall into the category of multi- A complete physical examination of the factorial inheritance of a threshold charac- infant with meticulous documentation of both ter-that is many genes, each with a relatively normal and abnormal features add up to very small effect that interact with the environ- specific syndromes. ment to determine whether the developing 2. Chromosomal Aberrations embryo reaches a threshold of abnormality. Patients with the more common trisomies These cases show a strong familial tendency (D, E and G) have very specific recognizable but do not conform to simple mendelian in- facial features associated with other malfor- heritance patterns and there are no demon- mations. Although the diagnosis can only be strable chromosomal aberrations. Diagnosis is confirmed by karyotyping, a high index of simple and for the majority prognosis is very suspicion by a knowledgeable clinician can good. help prepare the parents as well as assist the A relatively small number of patients with medical team in the neonatal unit outline a a cleft of the lip and/or palate are not of the treatment plan based on the expected prog- multifactorial inheritance category. These pa- nosis. Where corrective surgery may be rec- tients usually make up approximately 3% of ommended in certain patients with Down a clinic population (Fraser 1970) and present syndrome with a cleft, it is extremely unlikely with one or more additional structural abnor- that it be considered in a patient with Tri- malities. The majority of these patients have somy E. identifiable syndromes or associations. The 3. Other causes etiological factors in this latter group can be Included in this category are teratogenic classified in one of the following categories: substances such as drugs, alcohol or even heat 1. Major Mutant Genes known to cause congenital malformations in Numerous syndromes with a known men- the exposed fetus. Few drugs have definitely delian inheritance pattern include cleft lip been shown to cause clefts in man, however, it is extremely difficult to detect a drug that will cause a defect in only the cases with a Dr. Pashayan is Professor, Department of Pediatrics susceptible genotype. Also included in this and Director, Cleft Palate Clinic, Tufts-New England Medical Center, Boston, MA 02111. Address editorial group are syndromes that include clefts as a correspondence to Dr. Pashayan at above address. manifestation and are of unknown etiology. 534 Pashayan, CLEFT LIP AND/OR PALATE 55

In this presentation an attempt is made to Retardation Syndrome, Birth Defects, 12(5): 235-238, list syndromes, associations or sequences when 1976. ' Dr ca CHAPELLE, A., MarotEaux, P., Haru, N. and a given abnormality other than a cleft of the CrRaANROTH, G., Une Rare Dysplasie Osseuse Lithale de lip and/or palate is present. The clinician Transmission Recessive Autosomique, Arch. Fr. Pediatr., should find it easy to identify the given syn- 29: 759-170, 1972. ' drome by checking the specific table. Based Donan, M. A., Growth Failure, Cleft Palate, Ectodermal Dysplasia and Apparent Pancreatic Insufficiency. ?A on an accurate diagnosis the timing of surgical New Syndrome, Birth Defects Orig. Art. Ser., 13(3B): treatment, suspected prognosis and genetic 230-231, 1977. counseling can be offered. Eastman, J. R., and BixuEr, D., Facio-Cardio-Renal Syndrome: A Newly Delineated Recessive Disorder, References Clin. Genet., 1 1: 424-430, 1977. Ermorr, S. M., Pycyodysostosis: A review, J. Bone. Zoint AasE, J. M., and Smit, D. W., Dysmorphogenesis of Surg., 49-A: 153-163, 1967. Joints, Brain and Palate: A New Dominantly Inherited Erickson, A., Hereditary Syndrome Consisting in Recur- Syndrome, J. Pediatr., 73: 606-609, 1968. rent Attacks Resembling Brachial Plexus Neuritis, Spe- ABrvzzo, M. A., and Erickson, R. P., A New Syndrome cial Facial Features and Cleft Palate, Acta. Paediatr. of Cleft Palate Associated with Iris Coloboma, Hypo- Scand., 63: 885-888, 1974. spadias, Deafness, Short Stature and Radial Synostosis, EscomBar, J. I., and Yunis, J. J., Trisomy for the Proximal _J. Med. Genet., 14: 76-80, 1977. end of the Long Arm of Chromosome 13, Am. J. Dis. ALLpERpINE, P. W., Brownz, N. and Muzrpuy, D. P., Child, 128: 221-222, 1974. Chromosome 3 Duplication qg21- +qter Syndrome in FrasER, F. C., The Genetics of Cleft Lip and Cleft Palate. Children Carriers of a Pericentric Inversion inv(3)p2 Am. J. Hum. Genet., 22: 336-352, 1970. 5q21, Amer. J. Hum. 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58 Cleft Palate Journal, January 1983, Vol. 20 No. 1

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gland. coloboma

tus. angle

Microtia

temporalis, the ear

bones.

Asymmetry Cleft

der

Cavity.

inheritance;

(Van

Oral

recessive

and

Spectrum

syndrome

Lips

Autosomal

Syndrome

Lip-pit

syndrome

Mouth,

syndrome)

the

inheritance;

Congenital Woude

Robinow

Oto-palato-digital

Hallermann-Streiff

Facio-auriculovertebral

dominant

Anomalies

Autosomal

Anomaly

Fistulae

pits

lip Lip

Microstomia

Macrostomia

AD TABLE Pashayan, cLEFT LIP AND/OR PALATE 59

R. A.

M. D

1966

Dallaire

1971 1982

Hall 1977

1977 Smith

1974 Donlan

Eastman

Pashayan

AR Sporadic AD PAR AR PAR AD

epi-

toes. fail-

pal-

duct

retar-

and/

limbs.

broad

digital

serious

ventral

nostrils. missing

skeletal

Feeding

lip

persistent

to Partial failure

third

Cleft

abnormal-

deficiency.

and

eyelids,

and

Growth

mental

Punctate

Cleft

and

palate.

(Other

EEG

Flat

bones,

abnormal

ridge one

anteverted

mental

Nasolacrimal

frequency

severe

cleft

ankylosis.

Ptosis

second

eruption

with

Hypodontia.

with

high susceptibility

dysplasia.

clavicles.

screaming.

ears. Several

alveolar

Wormian

tip

Micrognathia.

involving hypoplasia.

shrill

tongue

crease, scaphocephaly.

Delayed

Oligodontia.

Moderate

face.

nasal

lower

limbs

Micrognathia,

Increased

glossopalatine

rotated syndactyly

Malar

Ectodermal

with

hypoplastic

hair.

anomalies.

Simian Plagiocephaly.

teeth.

relative

small

hypoplasia.

thrive.

Broad

ridges.

feet).

digits

ears.

blond

with

opening,

behavior

and

hypoplastic

Hypoplasia

the

posteriorly patterning,

dental

infancy.

Cardiac

Absent

hypospadias. of

oral

alveolar

Relatively

abnormalities.

Failure

insufficiency.

Sparse

and

with

strabismus.

ridge

early

(hands

palate.

teeth.

set in Irritable

Prominent

eczema,

Supernumerary

Small

kidneys.

birth.

absence

folds,

Microcephaly

Cleft

palate.

maxillary

calvaria.

Cleft

dermal

Low

root.

skin,

Pancreatic

cleft

Small dation. ities.

Broad

canthic difficulties infections. physis.

whorl Ciryptorchidism,

Micrognathia

teeth.

frenulum. Large fontanels.

complete abnormalities).

eruption ure.

Thin Horsehoe Neuromuscular

nasal ate. Ectrodactyly

or obstruction.

(OFD

Spectrum

II)

syndrome

(OFD

vertebral

syndrome*

dysplasia

syndrome

Web

syndrome

Mohr Smith-Lemli-Opitz

Oro-facial-digital

Facio-auriculo

Mohr Popliteal

OFD

Aglossia/Hypoglossia

Adactylia

Cleido-cranial Donlan

Eastman

EEC

tongue

ridge

tongue

Alveolar

Lobulated

Small

Teeth

60 Cleft Palate Journal, January 1983, Vol. 20 No. 1

et et

D. D.

Ref.

J. J.

R. R.

1971

1977

1971

1975

Gorlin

Gorlin 1982 1970

1976

Weaver Gorlin

Weintraug Smith Freire-Maia

Gorlin

«Gorlin

Inher.

Pattern

Sporadic

Sporadic Sporadic

Sporadic AD

An-

syn- Soft

cleft

eyes.

defi-

bone

limb

muscle

osseous

Enamel

set

Maxillary

palate.

and hypoplastic

partial

and/or

nipples.

Deep

Variable

anodontia.

Deafness-cup-

anomalies,

lip

Hypogonadism.

fingers.

Delayed

Cleft

hair,

Generalized

bridge.

tissue,

iris

Patchy

Hyperpigmentation.

fifth

Cleft

teeth.

sparse.

partial

bones.

nasal

teeth.

Sparse

hypoplasia.

and

Supernumery

Hypodontia.

anomalies.

long

that

disease.

formed

teratoma.

Broad

ears.

anhidrosis.

palate.

subcutaneous

keratoderma.

Microcornea,

fourth

hair

Clinodactyly.

atresia.

mid-face

Manifestation

heart

Skeletal

Malformed

crown

cleft

Hypodontia

ribs.

alae.

Wiry

duct

Partial

Micrognathia.

plantar adnatum.

palate.

deformed

Clinical

tubulation

secondary

conical

teeth.

Microtia,

mouth.

nails.

and/or

Diminished

and

Cleft

Congenital

lip

glands.

Large

Lacrimal

Hypodontia.

filiforme

ankylosis.

hypoplastic

spaced

camptodactyly

probably

Down-sloping

Increased

Cleft Palmar

sweat

dystrophic

deficiency.

nose,

and

wide

Oligodontia,

deficiency.

auricles.

fixation.

down-turned

syndactyly.

Microcephaly.

palate. palate.

palate,

Cleft

Cleft maturation.

hypoplasia. Small mass. Mental

Stapes

palate.

hypoplasia. dactyly Narrow

tissue

shaped

Absent ciency kyloblepharon hypoplasia. anomalies. Mental

Conical nipples.

Glossopalatine

Tetraperomelia.

dys-

(ODD)

membrane

syndrome

Fixation

ectodermal

syndrome

Stapes

teratomas

Syndrome

ankylosis

and

syndrome

oral

syndrome

buccopharyngeal

duplication

Wells

Persistent

Oral

Congenital

Weaver-Williams

Oligodontia

Oculodento-digital

Hay plasia

Freire-Maia Glosso-palatine

1.-(continued) Anomaly

TABLE

Pashayan, cLEFT LIP AND/OR PALATE 61

R. Ref

1966

1968

Shaw Bloom

1973

1970

1981

Schmickel

McNicholl

Pagon

ami-

preg-

Jewish

antagonist

Ukranian

trimester

acid Inher.

first Pattern

are

folic

table.

sporadic

during

are

another

(majority

Ingestion nopterin nancy

AR ancestry)

Majority PAD PAR

Majority

described

the

syn- and

age.

cleft

ears.

been mild

tend-

Cafe-

heart

small

lamb-

malar

(if

devel-

palate.

border

Hyper-

with

has

and

occipital

and Anterior

Propenc-

(butterfly

difficulty.

bone vertebrae.

Pilonoidal

wings

Prominent vitro

clinodactyly

Hypoplastic

and

Cleft

fibulae, to

and/or

foot.

colobomatous

micrognathia.

infancy.

concave

Colobomata

iliac

Prominent

ribs

Syndrome

Congenital

notching

Bell-shaped

bridge.

temporal,

club

Short

Synostosis

development

Retarded

erythema

Severe

growth Micrognathia

hypodactyly,

Small

during

Swallowing

insertion

vertebrae.

Dolichocephaly,

disorganization.

nasal

incisors.

area.

ossified

polydactyly,

palate.

malignancy.

rib

Hypertrichosis.

motor

flat

parietal,

Micrognathia.

antigonial thickening

palsy.

extremity,

fontanels.

soft

combination

Manifestation

anophthalmia.

deafness.

and

Broad

and

clavicles.

stature.

Retarded

skin.

lateral

inheritance;

problems

deficiency.

cellular convex

deficiency.

with or

posterior

the

folds.

equinovarus,

frontal, breakage. microphthalmia.

Facial

Tracheobronchiomalacia.

telangiectatic

lower

Microcephaly.

Wide

cortical

fistula.

iris

Syndactyly,

short

over

Short

short

Clinical

gross

Anomalous

upper

and/or

mental

nerve atresia.

sutures.

X-linked

growth

the

growth with

Feeding

with

and

Short

lymphoreticular rib.

Ichthyotic

Talipes

Cleft between palate.

Facial

with

palate.

outlet.

aborted).

maxilla.

dimple.

optic

femora.

epicanthic

tibia

thin

onset onset

dimpling onset

Micrognathia

Normal

Microtia

ears:

coronal

cleft

chromosome retardation.

soft Choanal

not Gaps

finger.

spots.

hypoplasia

brain

and

Absence

X-linked

develop

and

to pelvic

sacral

skin

the

fifth

Low-set dactyly. Severe

fetus eyes bones doid Prenatal

Micrognathia.

hypoplasia. area). au-lait ity

cyst, of Prenatal Large

ency telorism. bowing and

of bowing Prenatal

scapulae, thorax. Mental

wide Glossoptosis. cartilagenous malformations

Colobomata disease.

choroid opment. without

Tracheoesophageal

inheritance;

syn-

recessive syndrome

Adactylia

Autosomal

Syndrome

Mandible. dwarfism

induced

the association

syndrome

inheritance;

drome*

Aglossia/Hypoglossia

Aminopterin Bloom

Camptomelic Cerebrocostomandibular Charge

dominant

Anomalies

Autosomal

Anomaly

Micrognathia

TABLE

62 TABLE 2-(continued)

Inher. Clinical Manifestation Ref. Anomaly Syndrome Pattern Cleft

syndrome Mild to moderate growth deficiency. Flat facies with AD Spranger J et al

Conradi-Hunermann Palate hypoplasia of the malar eminences. Downslanting of 1971 palpebral fissures. Flat nasal bridge. Micrognathia. areas of punctate Asymmetrical shortening related to Journal, mineralization in epiphyses. Variable joint contractures. Scoliosis. Sparse and coarse hair. Follicular atrophoderma with large pores (orange peel skin). Cataracts. Hydram-

nios. Mild to moderate mental retardation. January al Cornelia de Lange syndrome Microbrachycephaly. Synophrys. Anteverted nostrils. Recurrence risk 2-5% Pashayan H et Long philtrum and carp-like mouth. Micrognathia. 1969

Dwarfism. Mental deficiency. Upper limb abnormalities. 1983, Congenital heart disease. Cleft palate. Hirsutism.

al Vol. Diastrophic Short stature of prenatal onset. Cleft palate and microg- AR Walker B. A. et nathia in 25% of cases. Respiratory obstruction and feed- 1972 Dwarfism 20 ing problems. Short tubular bones with broad metaphyses and flattened irregular epiphyses. First metacarpal small No. with proximal thumb. Symphalangism of proximal interphalangeal joints. Varus club foot plus limitation of 1 flexion at proximal phalangeal joints and of extension at elbow. Scoliosis +/- kyphosis. Soft cystic masses in au- ricle developing into hypertrophic cartilage in early infancy.

Donlan syndrome* Facio-auriculo vertebral Spectrum * H Familial micrognathia Isolated micrognathia. Cleft palate. Respiratory prob- AD Pashayan lems and feeding problems in the neonatal period. (No personal experience evidence of catch-up growth of mandible noted in adults). D. L. et al Femoral. Hypoplasia unusual facies syn- Small stature (secondary to short lower limbs). Microg- Sporadic Doentl drome nathia, cleft palate. Short nose with hypoplastic alae nasi. . 1975 Long philtrum and thin upper lip. Antimongoloid slant of palpebral fissures. Hypoplasia or absence of femora and fibulae. Club feet. Hypoplasia of humeri and re- stricted elbow movement. Pelvic bone abnormalities. Lower spine abnormalities. Normal intelligence. et al Fetal Pre- and postnatal onset growth deficiency. Mild to Severe maternal alcoholism Jones K. L. Alcohol syndrome. moderate microcephaly. Short palpebral fissures, ptosis. 1974 Maxillary hypoplasia, cleft palate and micrognathia. Fine motor dysfunction. Joint anomalies. Congenital heart disease.

Pashayan, CLErFT LIP AND/OR PALATE 63

D D

1982 1979 1976 1972

1975 1982

1976

Smith Smith Miller Bundy

Zackai Gordon Hanson

risk

day

hydan-

the

bathing.

disorder

the

one

compounds

parametha-

and

the

for

sauna

10%,

risk

diphenylhydantoin

related hr)

sporadic

The

about

features

38.9-40°C

33%

closely

pregnancy.

usually

intake

some

Trimethadione

illness

Prolonged

of pregnancy.

during

syndrome

known

additional

having

Febrile

(Dilantin)

PAR longer. not

AR AD dione toin

History Intake during an of

the

hy-

Mi-

cyst

and

Low

with Mild

septal

digital

palate.

Testic-

Mental

lip

nipples.

ridging.

Congen-

Seizures.

Neuronal

Hypopla-

nose

defects.

deficiency.

and

Congenital

vertebrae.

and

fissures.

bridge.

Hypoplastic

ovarian

Mid-face

evidence

severe

Cleft

lip

and/or

sinus.

forehead.

brachycephaly.

limb

Cervicothoracic

nails

Cleft

Cataract. Metopic

ventricular

genitalia.

nasal

lip

growth nipples.

(most

Cleft

palate.

ridge.

wide-spaced

upturned

Mild

loss.

palpebral

retardation.

Upper

Hypotonicity.

Cleft

aplasia.

Pilonidal

eyelids.

deficiency).

cleft radiological

Atrial

dysplastic

fontanel.

Prominent

Microphthalmia.

mandible.

Short

depressed

dysmenorrhea,

moderate

Accessory

Ambiguous

alveolar

mental

(LH

hearing eyebrows.

ears.

with

Renal

anomalies,

deficiencies

hernias.

deficiency.

and/or

Small

anomalies.

Ptosis

anomalies.

Broad

bridge.

mild

anterior retardation.

rib

Fallot.

Broad

Downslanting

limbs).

defects

(sometimes

lip

mild

ear

Rib

Limb

aplasia.

the

hypoplasia.

nasal

palate

upslant

growth

neck,

Wide

phalanges

inguinal Microcephaly.

Abnormal

Amenorrhea,

ears.

Micropenis

associations:

Conductive

cleft).

Mental

Cleft

ears.

dwarfism.

low

and

duct

with

and

disease.

side

External

onset

asymmetry

distal

Short

bony

degeneration.

lip

dysplasia.

Borderline

hypertelorism.

hypoplasia

Tetralogy

and

mid-face

disease.

the

atrophy.

heart

abnormal

Deafness

Microtia

Occasional

Micrognathia

Facial

Cleft

Gastrointestinal

ular

vertical Muscle

Somite

heart

postaxial

crognathia.

Malar Mullerian

heterotopias.

Micromelic Micrognathia. Micrognathia.

poplasia.

cup-shaped

broad

Mild Prenatal

palate.

ital

synophrys

defect. Prenatal

retardation.

Microcephaly.

Contractures.

Umbilical

Ocular

set

sia thumbs.

de-

syn-

syndrome-

(Tridione

syndrome*

(Dilantin

spectrum

(Steinert

syndrome*

ankylosis

syndrome

induced

dwarfism

syndrome

myotonica)

dystrophy

association

syndrome

dystrophia

Myotonic

Miller Murces fects

Hallermann-Strieff Micrognathic Hyperthermia

drome).

Fetal Hydantoin drome).

Fetal Glosso-palatine Trimethadione

64 Cleft Palate Journal, January 1983, Vol. 20 No. 1

Ref.

1974

1960

1980

Berrgio

1970

Lewis

1974 Gaber

Gorlin

Levi

Bowen

Inher.

Pattern

recessive

PAR

Sporadic

X-linked

Ex-

hy-

dis-

and cor-

Full

Mi-

sub-

with

from

and/

cryp-

hypo-

Men-

upper

hyper-

epithe-

palate.

valgus.

microg-

webbed

set

problems

palate.

moderate

eyelashes

heart

line

leading Antimon-

loss

palate.

eruption

penis,

(U-shaped).

keloids,

cleft

(involves

rate

the

Low

micrognathia.

present.

Skeletal

calvarium

Alopecia

Cleft Preaxial

eyelids,

and

Cubitus

intestinal

Cleft

equinovarus.

hairline,

nevi,

Mild

Small

fibrosis

Arrhythmias.

Feeding

years

thin

Occasional

Micrognathia.

palate.

along

Abnormal

skin

Delayed

Congenital

dysplasia).

(growth

thin

joints.

Short

Skin

five

the

ptosis

Talipes

dysostosis.

leading

strabismus:

and bones,

Thin

defects).

occasionally

mouth.

arteries). palate.

thrive.

posterior

radial recession.

Manifestation

anomalies.

equinovarus.

fissures.

excavatum.

bones.

column.

Micrognathia.

folds,

the

obstruction.

Periarticular

fontanels.

early

and

prominent

cleft

Toe

septal

appendages

Low

tongue

follicles.

degeneration

frontal

Clinical hypertelorism.

retardation.

pectus

mandible

malar

Talipes

trabecular

tract

failure

cholesterol.

nails.

Micromelia.

keratoconus

mesenteric

palpebral

small

vertebral

flexed

angle

and

hands.

hair

(thumb

the

High-arched

micrognathia

of stenosis,

Flat

Smooth

Epicanthic

auricles.

Thin

Mandibulofacial

Posterior

hypoplasia

chest,

and

the

defect.

serum

Ocular

Mental

lead

and

fat.

skin.

Premature

lids.

ossification

myopia,

rotated

Microtia.

rate).

partially

respiratory

bone

aorta

dysplasia

may

slanting

Atherosclerosis

septal

fistulae

Hypoplastic

Shield

stature.

nose.

stature.

deficiency

(pulmonic

tragus

lower

abnormal

retardation.

female.

ternally

Flat cheeks. teeth.

normal delay

plasia, elevation

lium. onary,

stiff

cutaneous degeneration Upper

Facial Hypoplasia which

Glossoptosis.

nathia.

perelastic

Atrial

torchidism.

neck.

Abnormalities ease

telorism,

Blind the

Short or

limb goloid on

in Small

tal crocephaly

syn-

cava

syndrome)

vena

(Turner-like

dwarfism

Syndrome

dysostosis

superior

sequence

left

syndrome

(Hutchinson-Gilford

Robin

acrofacial

Pseudo-diastrophic

Progeria

Pierre

Persistent drome

drome)

Noonan Nage

2-(continued) Anomaly

TABLE Pycnodysostosis of Marateaus and Lamy Small stature. Osteosclerosis with tendency toward trans- AR Elmore S. M. verse fracture. Frontal and occipital prominence. Delayed 1967 closure of sutures. Wormian bones, absence of frontal sinuses. Hypoplasia of facial bones. Prominent nose. Mi- crognathia. Partial anodontia with delayed eruption. Dysplasia or absence of acromian end of clavicle. Acro- osteolytic dysplasia of distal phalanges (index finger most common). Wrinkled skin over dorsum of distal end of fingers. Flattened nails. Mental retardation.

Radial aplasia Thrombocytopenia with absence or hypoplasia of mega- AR Shaw S. et al Thrombo-cytopenia syndrome karyocytes. Anemia out of proportion to apparent blood 1956 loss. Usually bilateral absence of hypoplasia of radius with associated ulnar hypoplasia and defects of hands, legs and/or feet. Thumbs are present. Congenital heart disease. Micrognathia. With advancing age, the severity of the hematological disorder becomes less profound. 40% of patients expire during infancy as a result of hemor- rhage.

Robinow (Fetal face syndrome) *

Rolland syndrome Short stature. Short broad tubular bones with metaphy- Sporadic Langer L. O. et al seal widening. Accelerated carpal bone maturation. Bow- PAR 1976 ing of legs, thighs and forearms. Short broad pelvis with wide flared iliac wings. Vertebral anomalies. Respiratory distress. Micrognathia. Cleft palate. "

Rubinstein-Taybi syndrome Short stature. Retarded bone age. Micrognathia. Anti- Unknown Simpson N. E. et al | mongoloid slant of palpebral fissures. Maxillary hypopla- Majority are sporadic Estimated recur- 1973 sia with narrow palate. Beaked nose with nasal septum rence risk is 1% Pashayan, extending below alae. Epicanthic folds, strabismus. Au- ricles low set and/or malformed. Broad thumbs and first toes. Cryptorchidism. Nevus flammeus. Mental retardation and EEG abnormality. CLEFT

Sekel syndrome Prenatal onset of marked growth deficiency. Mental re- AR McKusick V. A. with premature synostosis. Hy- 1967 tardation. Microcephaly LIP poplasia of facial bones with asymmetry. Prominent nose.

Low set and malformed auricles. Clinodactyly of fifth AND/OR finger. Simian crease. Hypoplasia of proximal radius. Dislocation of hip joints, hypoplasia of proximal fibula. Eleven ribs. Cryptorchidism. PALATE Silver/Russell syndrome Small stature of prenatal onset. Asymmetry most com- Most are sporadic (? single mutant gene Silver H. R. monly affecting extremities. Clinodactyly of fifth digits. representing fresh mutation 1964 Triangular facies with downturned corners of mouth. Micrognathia. Cafe-au-lait spots. Delayed bone age. Sex- 65

TABLE 2-(continued) 66 Inher. Anomaly Syndrome Clinical Manifestation Ref.

Pattern Cleft

ual precocity out of accordance with level of osseous

maturation. Mental deficiency reported occasionally. Dis- Palate location of radius, ulna and/or hips. Hypospadias. Ele- vated urinary gonadotropin. Journal, Smith-Lemli opitz syndrome* dysplasia congenita Prenatal onset growth deficiency. Variable flat facies AD Spranger J et al

Spondyloepiphyseal January with motor hypoplasia and cleft palate and occasionally 1970 micrognathia. Myopia, retinal detachment. Short trunk with ovaloid flattened vertebrae with narrow intervertebral disc spaces, odontoid hypoplasia, kyphoscoliosis and lumbar lordosis. Barrel chest with pectus carinatum. Lag 1983, in epiphyseal mineralization. Coxa vara. Diminished joint mobility at elbows, knees and hips. Muscle weak- Vol. ness, easy fatigability and hypoplasia of the abdominal muscles. 4 v 20 No. Stickler syndrome Progressive myopia (8-18 diopters) retinal detachment in AD Herrmann J. et al

Progressive arthro-ophthalmopathy first decade of life, secondary glaucoma and blindness. 1975 1 Sensorineural deafness. Micrognathia, glossoptosis and/ Stickler G. B. et al or cleft palate. Bony enlargement of joints with irregular 1967 articular surfaces, pain and stiffness. Mildly flattened vertebral bodies with irregular epiphyseal surfaces and narrow intervertebral area. Kyphosis and sometimes scoliosis.

Treacher Collins Antimongoloid slant of palpebral fissures, lower lid colo- AD (60% represent fresh mutations) Rovin S. et al bomas with partial or total absence of lower eyelashes. 1964 Malar hypoplasia. Micrognathia, cleft palate. Microtia (+/- absence of external auditory meatus). Conductive hearing loss. Projection of scalp hair onto cheek (tongue hair). Absence of parotid gland occasionally noted. Nor- mal intelligence. Mild forms may present with hypoplastic zygomatic arch.

Turner syndrome Small stature evident at birth. Abnormal auricles. Epi- Faulty chromosomal distribution leading Turner H. H. canthic folds. Narrow maxilla and palate. Micrognathia. to XO individual. The paternal sex chro- 1938 Low posterior hair line. Webbed posterior neck. Cubitus mosome is more likely the one to be valgus, congenital transient lymphedema with residual missing. (Diagnostic tests: buccal smear puffiness over dorsum of fingers and toes. Short fourth and chromosome analysis) metacarpals and metatarsals. Narrow hyperconvex and/ or deep set nails. Mild pectus excavatum. Bony dysplasia with coarse trabecular pattern most evident at metaphy- seal ends of long bones. Excessive pigmented nevi. Horse-

Pashayan, CLEFT LIP AND/OR PALATE 67

R. et

Ref.

1960

1981

Wildervanck éhprintzen

1971 1971

1969 1966

Pashayan

Bixler

Gorlin

Appelt

known)

case

Inher.

Pattern

familial

table.

dominant

(one

another

X-linked

PAD

Sporadic Multifactorial AR

described

in-

af-

95).

ger-

de-

En- been

Her-

hair.

con-

defi-

upper

aorta.

hands

defect

lower

degree

slant

Narrow

squared

Cardiac

has and/or

kidneys.

measure-

Microgna-

scalp

I.Q.

lip

first

and

stature.

higher

reduction

palate.

Slender

Cardiac

Growth.

lids.

postaxial

absence

palate.

flatness.

ectopic

Syndrome

their

Cleft

prevelance (mean

also

velopharyngeal

cleft

limb

and

Small

Ectropion

broad

cleft

coarctation

intraocular

Abundant

lower

pelvis.

and

Malar

Micrognathia.

defect.

The

Antimongoloid

Manifestation

cases

are

Tetraphocomelia...

anomalies.

clitoris.

(with

and/or

microtia,

and/or

wider

renal

Preaxial

joints.

and/or

disease

70%

lip

heart

hypoplasia

infancy.

inheritance; lip

Clinical

controls.

nose

10%

cleft

disability.

Microtia.

submucous

individuals

show

Digital

hypertelorims.

Microcephaly.

heart

penis

Gleft

with

individuals.

which

Auricular

Colobomata than Cleft

palater.

dysostosis.

umbilical).

X-linked

Learning

fects.

fected Ocular

genital ment eyelids.

Hypertelorism,

ciency; Congenital larged Affected

Hypertelorism.

cleft double

(overt

relatives

Prominent

Hypotonia

Hyperextensible

deficiency.

cases

fissures.

dysgenesis,

retardation.

retardation

elements.

X-linked

palate

root).

kidney,

lower

(inguinal

digits.

20%

thia.

palpebral Mandibulofacial!

and

nasal

nias

palpebral Mental

anonralies.

and

minal Mental

Cleft in competence).

shoe Ovarian

inheritance;

palate

(pseudothalidomide

syndrome

recessive

cleft

Syndrome

Autosomal

and/or

syndrome

Region.

syndrbme

syndrome

lip

syndrome

Clefting/ectropion

Cleft Bixler

syndrome)

Appelt

facial

Ocular

the

inheritance;

Wildervanck-Smith

Velo-cardio

dominant

Anomalies

Anomaly

Autosomal =

Hypertelorism AD

Table 68 Cleft Palate Journal, January 1983, Vol. 20 No. 1

A al

al al et al

et et S.

Ref. J. et J.

A M.

E. R. R.

Chapelle

J. ° C.

La 1976

1972 1969 1973

1976 Gorlin

De 1969 Ide 1974 Aznedo

Gorlin Opitz Erickson

limi-

sex

male Inher.

Pattern

predominantly

with AR

AR AR Sporadic

tation

lip

ear

an-

epi-

and

eye-

fore-

ears.

ulna.

Lim-

retar-

arter-

Deep

ocular

abnor-

Crypto-

nostrils,

lip.

Cleft

Wide-set

and

peak,

short

Antimon-

Abnormal

growth

anomalies,

ears,

lateral

palate.

palate. Winging

ductus

external

stippled

cleft Other

Cupped

fissures.

Mental

to neuritis.

set

defect.

root,

bridge.

Prominent

Hair

fibula

cleft

Cleft

Widow's

occultum.

patent

Low

elbows.

nares.

duct

lethal.

Vertebral

Median

nasal

plexus

asymmetry.

syndactyly.

eyes.

Manifestation

defect.

colobomas

humeri

cataracts, palpebral

the

lethal.

and/or

Atresia

extending

ovale,

flat

Flat

Hypospadias.

ear

bifidum

the

lip

Triangular

and

Facial

notched

face,

dwarfism.

Lacrimal

Clinical

brachial

notched

Cleft

phalanges.

palate.

Commonly

cutaneous

hypertelorism.

hypoteloric

bones.

forehead

foramen,

Flat

Middle

slant

femora

Commonly

cranium

abnormalities.

extension

scapulae.

and

head. physes. dation. Hypertelorism,

Short Micromelic hypertelorism. Double ios:s

patent phthalmos. Partial

curved and/or lateral brow. Hypoplastic genitalia.

canal. terior

Hypertelorism.

Ocular nostrils,

other malities. ited

Recurrent the

goloid

set

syn-

neuritis

plexus * disease

dwarfism

Cryptophthalmos .

Syndrome

syndrome dysplasia

branchial

dysplasia

syndrome* Rhizomelic

syndrome syndrome

palate

Chapelle syndrome*

De Fraser Cleidocranial Conradti's

drome

Frontonasal Opitz

OPD Pseudodiastrophic

Opitz-Frias

Cleft syndrome Anomaly

3.-(continued)

Hypotelorism

TABLE

Pashayan, CLEFT LIP AND/OR PALATE 69

al M.

1977

1960

1971 1970 1976

1972 1981

1963

Marden Abruzzo

Davis Gorlin Bowen

Fuhrmann

1978

Wand

Walker

Griess

abnor-

sporadic

may

chromosomal

group

dominant

secondary

?2AD X-linked

AR AR AD PAR AD AD

mality Heterogeneous

lip

lo-

de-

hy-

In-

Ra-

(ex-

Na-

Cleft

with

pres- feet).

folds.

motor

stature.

ankylo-

infancy Hetero-

with

toes,

Cleft

and

growth

retardation.

hypoplastic

contractures.

cyclops).

defects

usually

Short

deafness.

abnormalities.

mental

Hypoplasia

adnatum.

survive

patients

(hands

Epicanthic

are

Vitiligo.

from

hypotelorism

nostril.

microcephaly.

Synophrys.

will

facial

ears.

mental

adnatum.

oligodontia,

Other

Joint

syndactyly

Hypotonia,

vary

present

filiforme

degree

orbital

single

bossing.

Large

Deafness.

Marked areas,

Hypospadias.

Sensorineural

may

median

Syndactyly

Occasionally

filiforme

would

palate.

canthorum.

hypotonia.

malformations

retardation,

variable

Frontal

irides.

degree

synechiae

palate.

retardation.

region.

abnormalities.

case

palate.

abnormalities,

cartilage

synostosis.

coloboma.

childhood.

with

holoprosencephaly

and/or

deformity

Cleft dial

perpigmented malar Muscular Iris

and/or blepharon EEG Blepharophimosis.

lip

ficiency. Growth

Other Mental

Dystropia Lateral Ankylbblepharon

chromia

Ectrodactyly:

nasal

bar retardation.

sal and tracranial

ent treme variable

Spectrum

syndrome

(Ectrodactyly

syndrome

synechiae

syndrome*

syndrome

deformity

syndrome

Lange

syndrome)

syndrome*

claw

Amstrong

palate/lateral

syndrome*

palate

Marden-Walker Abruzzo-Erickson

Hay-Wells

Davis-Lafer

Clefting/ankyloblepharon

Lobster

EEC Cleft Waardenburg cleft

Cornelia

EEC

Holoprosencephaly

Bowen

abnormalities

proface

sparse

titis

abnormalities

Eyelid

Intra-ocular

Dacrocys Eyebrows Eyebrows

70 Cleft Palate Journal, January 1983, Vol. 20 No. 1

Ref. I.

et D

1979

1971

Pyeritz

1969

Hsia

1974 1982

Phillips

1977

Siggers Smith

Lowry

utero

virus

Inher. Pattern

Rubella

to AD AR PAR

Sporadic PAR Exposure ?Sporadic

the

pal-

stiff

my-

fifth

dia-

Cleft

face.

Ecto-

Cleft glau-

glau-

Deaf-

Atrial

palate.

cleft

the

Seizures.

Lordosis.

Encepha-

the

Large, colobomas.

fingernails.

Severe

of retardation.

Cleft

Round

Scoliosis.

Microcephaly.

neck.

infections.

Cataract,

Cataract. and/or

Proptosis,

feet.

kidneys.

deformities

joints

lip

bowing.

development.

Mental

Short

Macular

Arachnodactyly.

nose.

Club

Manifestation

dwarfism.

Cleft

hyperconvex aneurysm.

anomalies.

flexion

Tibial

Deafness.

Eventration

respiratory

Craniosynostosis.

dental

abnormalities.

Polycystic

detachment.

joints.

Clinical

beaked

Aortic

hypoplasia.

deficiency.

Narrow

valgus,

Other

Cardiac

defect.

interphalangeal

Delayed

retinal

palate.

Recurrent

painful

lentis.

Dolichostenomelia. pia palate.

Polydactyly.

locele.

Microphthalmia.

ate.

Growth Hallux

fingers.

distal

Growth Microcephaly.

Disproportionate

Mid-face Kyphoscoliosis.

and ness. palate. Microcephaly.

opia, Prominent

coma. phragm.

septal Cleft

de-

spectrum

(Cryptophthalmos

syndrome

Syndrome

induced

syndrome*

syndrofne syndrome

syndrome*

syndrome

association

syndrome*

Marfan

Meckel

Phillips-Griffiths

ODD

Charge Conradi's

Fraser

Hay-Wells* Hyperthermia fects* Rubella

syndrome)

Kniest

Lowry-MacLean

3.-(continued)

Anomaly

TABLE -

Pashayan, cLEFT LIP AND/OR PALATE 71

et al

Ref.

1982

1968

Smith

Aase

1977

1970

Yong Spranger Inher. Pattern

?AD

table.

ear.

Malformed

another

Cystic

Sporadic

thumb.

described

dislocation.

been mi-

and

pig-

Hip

has

and/or

disease.

develop-

(neck

lip

Hitch-hiker's

Retinitis

heart

Mild

Manifestation

Syndrome

Cleft

foot.

detachment.

stature

Chorioretinitis;

* malformation.

hepatosplenomegaly.

Club

Clinical

short

stature.

myopathy.

Retinal

Congenital Seizures.

opacity.

Walker

inheritance;

Short

delay.

Myopia.

Dandy corneal

Contractures.

X-linked

palate. mental

mentosa.

Undifferentiated

trunk).

Disproportionate

Thrombocytopenia, crophthalmia. coma,

stature.

X-linked

Short

Hydrocephaly.

ears.

congenita

inheritance;

dysplasia

recessive

spectrum

(Cryptophthalmos

Autosomal

syndrome*

Syndrome

syndrome

dysostosis*

dwarfism

syndrome

Ear.

Stickler Yong

Spondyloepiphyseal

syndrome*

association

syndrome*

the

inheritance;

Fraser

syndrome)

Facioauriculovertebral Diastrophic

Cleidocranial

Bixler Charge

Abruzzo-Erickson

Aase-Smith

dominant

Anomalies

and/or

Autosomal

Anomaly

Deafness

Microtia AD

TABLE

72 Cleft Palate Journal, January 1983, Vol. 20 No. 1

et L.

Ref.

I. S. D.

1972

1974

1960

Polant

Temtamy Wildervank sporadic

unknown ?Sporadic Etiology

majority AD Inher.

Pattern to atresia. defects. ~

polydactyly, (secondary cardiac esophageal preaxial

other Deafness with and artery.

fistula palate. hypoplasia, defects

TE. Cleft

radial paralysis. unbilical septal or fistula.

f Single

thumb

vertebrae. Abducens

Manifestation ear). (23%) Ventricular without animalies: deafness or anomaly. limb

Clinical

cervical middle

including

Deafness. of

with the frequent lower Renal and/or

anomalies. of of

less fusion. fontanels palate

dysplasia fusion anomaly atresia Rib Microtia Large Defect Cleft

Other Block Vertebral

Radial anomalies

Anal Cervical

syndactyly.

de-

(mandibu-

spectrum

dwarfism

syndrome*

(OFD

syndrome*

Syndrome induced

syndrome* syndrome

syndrome

syhdrome* Collins

association

syndrome*

syndrome* dysostosis)

phenotype

association

syndrome*

Hay-Wells

Pseudodiastrophic

Meckel Hyperthermia VATER fects*

Klippel-Fiel lofacial

Miller

Mohr Murces

Stickler

Waardenburg

OPD

Weaver-Williams

Turner Wildervank Treacher

(continued)

4.-

Anomaly

TABLE

Pashayan, cLEFT LIP AND/OR PALATE 73

R. R.

Ref.

1976

1970

1982

Gorlin

Gorlin Smith Inher.

Pattern Sporadic

Multifactorial

Fa-

side.

complete

pinnae.

the

table.

and

ipsilateral

side

another

alae

palate.

same

Cleft

nostril

the

described

cartilages

Manifestation

been

Absent

deficiency.

has

cartilage

Clinical

palate.

Mental

Hypoplastic alar

cleft

Syndrome

the

and/or

lip

lip.

hemangiomas.

inheritance;

cial

Tetraphocomelia.

Cleft

Hypoplasia

cleft

X-linked

(complete

X-linked

table

sequence

syndrome*

syndromc*

(see

anomaly

inheritance;

syndrome)

Syndrome

syndrome

syndrome*

dysplasia*

palate

bilateral)

Lange*

syndrome*

syndrome* or

syndrome*

recessive

Mohr

and

proboscis

syndrome*

Dilantin

II*

lip

Camptomelic

Hay-Wells

Hallermann-Streiff

OPD

Robinow Fetal

Fetal

Pseudothalidomide

(cfyptophalmos Waardenburg Apert Cornelia

OFD Lateral ODD

Hallermann—Streiff

Autosomal Fraser unilateral

Conradi's Cleft .Holoprosenéephaly*

‘

Nose.

tip

the

inheritance;

colobomata

antiverted

dominant

with nares

Anomaly

bridge

Anomalies

nasi

bridge

short

nasal

alae

Autosomal

nasal

the

Flat

Broad

Small

Hypoplasia

of AD

TABLE TABLE 5.-(continued) 12

Inher. Anomaly | Syndrome Clinical Manifestation Pattern Ref.

Cleft Palate Cleidocranial dysostosis*

Conradi-Hunermann syndrome* Journal, Fetal Dilantin syndrome*

Kniest syndrome* January

Mohr syndrome* (OFD II)

Prominent nose Velo-cardiofacial syndrome* 1983,

Vol. 20 No. 1

TABLE 6. Anomalies of the Neck. AD = Autosomal dominant inheritance; AR = Autosomal recessive inheritance; X-linked = X-linked inheritance; * = Syndrome has been described in another table.

Anomaly Syndrome Clinical Manifestation Inher. Ref. Pattern

Short or webbed Klippel-Feil * Turner phenotype* Wildervank syndrome*

Pashayan, cLEFT LIP AND/OR PALATE 75

J. J.

J. et

Ref

D D

1982

1969

1976

1975

Smith Smith

1976

1974

Gorlin

Aaintl

Juberg

Gorlin Battle 1976

Inher.

Pattern

PAR PAR

Sporadic Sporadic

Sporadic

Unknown

table.

and

Limb

spleen

Micro-

radii. palate.

fibulae.

syndac-

reported.

another

hypoplastic

and

Cleft

short

radiation

Distal

been

Variable

with

Microphthalmia.

also

facies.

femora

described

limbs.

thumbs,

encephalocele.

nose

Microphthalmia.

marginal

Flat

malformations

have

been

absent

Hypodontia.

placed dorsal

has

Short

digits

ulnar

ulna

defects.

of Encephalocele.

hypoplasia.

peromelia).

distally

Manifestation

Short

fissures.

Syndrome

association

Skeletal

instead

Posterior

and

deformities.

reduction

Micrognathia.

Clinical

cerebellar

amputations

palate.

philtrum.

Microcephaly.

palpebral

with Facial

aplasia

and Occasional

and

oligodactyly

palate.

cleft

dqﬁcieflcy.

inheritance;

long

ankylosis.

hypoplastic

ulna

dislocations.

clefts.

Radial

slant

(from

the

lip-palate.

joint

Cerebral

and/or

segments.

growth

X-linked

facial

defects.

lip

constrictions

cartilages,

Cleft

kidney.

Multiple cephaly.

Microcephaly,

anomalies

Glossopalatine

Other

alar internal Mongoloid

and Cleft Aplasia Mental Ring tyly.

Bizarre

Cleft

X-linked

up-

syn-

band

inheritance;

facies

(Streeter

absence

syndrome

recessive

(Adactylia

syndrome

unusual

(pseudothalidomide

syndrome* syndrome*

syndrome

Syndrome

syndrome*

syndrome

ankylosis

aplasia

Autosomal

Lange

deformity

band

bone

de hypoplasia

syndrome*

syndrome

Chapelle

Limbs.

syndrome*

limbs

the

Larsen

Meckel-Gruber

Freira-Maia:syndrome*. Forearm

Glossopalatine

EEC drome De

per Femoral

Cornelia

Congenital Clefting/ectropion

syndrome)

drome*) Amniotic syndrome) Appelt

Aglossia/Hypoglossia

‘Juhbert—Haywafd

inheritance;

dominant

Anomalies

Anomaly

deficiency

Autosomal =

Limb

AD TABLE

76 Cleft Palate Journal, January 1983, Vol. 20 No. 1 al al al

et al et et

C. et J.

J. S D. R.

D D

Ref. 1982

1976 1976 1970

1972 1982

Smith Kreiborg Gorlin Wallace Smith Gorlin injestion pregnancy PAR AR during AR AD AD

Thalidomide

Inher. Pattern

sec-

ears.

nasal

heart

lungs.

palpe-

palate.

incom- medial

palate.

mental

growth

Exoph-

degree

palpebral

Byzantine

orbits.

syndactyly

the

cleft

with

Polydactyly.

between

esophagus

Deviated

lower

clitoris.

and

Congenital

Malformed

Profound

slant

neck.

slanting

hypoplastic

Polyhydramnios.

Shallow

the

lip

which

without

genitalia.

eyelid

eyelids.

associated

Cryptorchidism,

uterus.

Symmetrical

Atresia

Short

syndactyly

the

upper

are

palate

with

phocomelia

internal

retardation.

palate.

horseshoe).

Ptosis

partial

cases

kidneys.

lip

antimongoloid

Micrognathia.

hemangioma.

Antimongoloid

hydrocephalus,

bicornuate

from

notch

narrow

anomalies.

hypoplasia.

Enlargement

Cleft Manifestation

and

and/or

Some

mental

Cleft

hemangioma.

cloboma

Ear

cage,

Very

sclerae).

(polycystic,

limbs.

capillary

Fallot.

Central

Cutaneous

asymmetry.

(varying Clinical

rib

hypoplastic

facial

onset.

Mid-face

Severe

external

the

stocking).

palate.

clouding,

Hypertelorism.

(bluish

Facial

defect.

Cryptorchidism,

Hypertelorism

Mid-face

and

anomalies

fissures.

prenatal

deformed

Micrognathia.

Microtia,

Cleft

Proptosis.

Hypomelia

eyes

Tetralogy

heart

Polycystic

corneal

third

(glove

Brachydactyly.

region.

Renal

shortening

hair.

limbs,

synostosis.

palate. feet.

development

reduction).

fissures.

and

digits

plete Prominent

Cleft Club Hypertelorism. fissures.

Microbrachycephaly. deficiency limb Severe thalmos, Phocomelia. Short

Sparse disease. canthus duodenum. Congenital Cran retardation. Craniosynostosis.

bral shaped.

of septum. ond Syndrome

(Cryptophthalmos

(pseudothalidomide *

syndrome*

syndrome

syndrome association

syndrome

syndrome*

association

syndrome*

syndrome

Miller

Pseudothalidomide Murces Roberts

syndrome)

Fraser Saethre-Chotzer

Tetraphocomelia VATER Wallace Apert syndrome)

Thalidomide 7.-(continued) Anomaly

TABLE Syndactyly

Pashayan, cLEFT LIP AND/OR PALATE 77

1976

1970

1974

1977 Moroteaux

Gorlin

Spranger 1982

1969 Hausam

1978 Smith

Gordon

Gewitz case) sporadic

are familial AR

Sporadic

(one Sporadic

Majority

PAR AD

Sporadic

and

Flat

base

Cleft

Poly-

utero

palate.

olfactory

Persistent

skull

phalnages

deficiency.

head.

elbows

Cleft

foot.

proptosis.

syndrome.

except

Absent

large

Death

middle

Growth

each

and

bones

Ocular

death

uterus.

vertebrae.

vessels.

all

Absent

toenails.

toes

trunk

Contractures

Cleft

infant

great

kidneys.

and

small

thumbs.

Bicornuate

craniofacies.

hairline.

Sudden

blob-shaped

abnormalities.

fingernails

tract.

palate.

Absent

Hypoplastic

Micrognathia.

anus.

foot.

Underossification

palate.

Three

fifth

posterior

Transposition

Cleft

Other

cava.

Asymmetric

Club

cleft

set

furrows.

Disproportionately

hands.

respiratory

Absent

thumbs.

vena

dwarfism.

palate.

Low

pterygia.

Imperforate

and/or

deficiency.

after.

Plantar

facies.

broad

Cleft

lip

clavicles.

superior

Multiple

Micromelic

Hypoplastic

shortly tract. left

(varies). Short, and

syndactyly

palate.

knees. forehead.

Craniosynostosis.

Mental

Coarse

Camptodactyly.

Cleft

syn-

finger

index

syndrome)

(Saldino-Noonan

polydactyly

and

rib

syndrome

syndrome*

(Gordon

dwarfism

dysostosis*

dwarfism

Short

syndrome

syndrome*

metacarpal pterygia

syndrome

syndrome*

Multiple

ODD

Micrognathic

Marfan

drome)

Hay-Wells Majewski

syndrome; Lowry-MacLean

Diastrophic Hausam

Conradi's

Coffin-Siris

Cleidocranial Camptodactyly

Accessory abnormalities

Digital 78 Cleft Palate Journal, January 1983, Vol. 20 No. 1

al al

et et

et A. Ref.

S. D al

D et

R. B

1976 1982

Gorlin Smith

Ref. 1982

1968

1971 1975 Smith

Rapp Rudiger Say

Inher.

Pattern

pal-

De- Sporadic

AD AR AD Inher. Pattern

Cleft

proptosis

table.

V-shape

tongue.

the facies. Simian

even

thumbs.

another Hypertelorism.

Ocular

Large

Hypoplas-

Absence

Inverted Coarse hands.

hand.

nose.

hand

fingers.

sutures).

Adducted

described the

strabismus.

anodontia.

the stenosis.

nails. of

been

sagital

has

Tapering

Partial

Parrot-like

thumbs.

and

divergent

Manifestation Ureteral

Syndactyly

Dystrophic

teeth.

Arthrogryposis.

stature.

placed

Hypoplasia

Manifestation contractures

Syndrome

maxilla.

major.

Clinical

= without

hair.

side.

life.

Short lambdoidal spaced fingernails.

defects. Clinical

wiry Flexion and

ears.

with

Proximally

Pectoralis

Rib

year

and widely

affected

Microcephaly.

(coronal,

inheritance;

Hypoplasia

Large

orbits

first

the fingers

Thin

areola.

defect

phalanges. retardation.

X-linked Small

bossing.

during

synostosis.

and

Peg-shaped

arm

shallow

distal

Unilateral nipple

whole Hyphidrosis.

Lethal creases. Growth Microcephaly. tic ate.

Cranio Craniosynostosis

due Frontal palate.

X-linked

inheritance;

dysplasia '

syndrome)

Syndrome

recessive .

(Mohr

dwarfism

ectodermal syndrome*

Autosomal

Syndrome

AR syndrome syndrome*

syndrome*

anomaly

syndrﬁme*

Cranium. syndrome*

I II

syndrome

the

syndrome* Phillips-Griffiths

Poland Pseudodiastrophic

OFD

OFD OPD Rapp-Hodgkin Rolland Rudiger

syndrome

Say

inheritance;

Apert Christian Crouzon

dominant

Anomalies

7.-(continued)

Autosomal

Anomaly Anomaly

TABLE

AD Synostosis

TABLE

Pashayan, CLEFT LIP AND/OR PALATE 79

1971

1982

Palant

Smith

1982

Smith

Multifactorial

pal-

set

shape

life.

limbs.

Cleft

deep

aspect

with

and

lower

Triangular

shunting.

anteromedial

incompatible

Deafness.

requiring

Almond-shaped

palate

Paresis/paralysis

meatus.

cleft

Prominence

deficiency.

defects.

toes.

auditory

Hydrocephalus

and/or

lip

Mental

vertebral

Cleft

Atresia

palate.

infections.

stature.

sacral

Clinodactyly

Cleft

tract

septum.

Short

tip.

cranium.

palate.

urinary

nasal

foramina.

Cleft

defect

optic

Bulbous

wrists.

Microcephaly. eyes.

ate. Frequent

Thoracic/lumbar

Bony

viation

defects*

band)*

(Streeter

syndrome*

spectrum

syndrome*

syndrome

induced

syndrome*

band

syndrome*

Gruber

syndrome

syndrome*

Aase-Smith

Weaver-Williams

Say

Robert

Palant

Myelomeningocele

Meckel

Lowry-MacLean

Hyperthermia

Holoprosencephaly Hausam

Jubert-Hayward Coffin-Siris

Amniotic Anencephaly

Saethre-Chotzen Cerebrocostomandibular

Hydrocephalus Microcephaly 80 Cleft Palate Journal, January 1983, Vol. 20 No. 1

al J. al

et Ref. et

R.B. R.

N N

1981

1971

Giess 1976 1981

Lowry Gorlin Geis

recessive Inher. Pattern

Multifactorial AR Sporadic

X-linked

and

with

Cleft

palate

death.

lip

table.

and

7.7%;

Cleft

patients

lip

another

For

cleft

Intrauterine

16.7%.

6.7%.

artery.

described

incompetence

Bilateral

been

syndrome

palate.

disease a

5.3%;

has

pulmonary

13.6%.

and

Cleft

heart

right

palate

feet.

Manifestation

Syndrome

palate

palato-pharyngeal

and

disease

Club

Cleft

lip

Clinical

congenital

with

heart

Abnormal

cava.

cleft

4.3%.

16.7%.

9.1%;

inheritance;

rate

vena

only

arteriosus. congenital

palate

X-linked

Unilateral

superior

syndrome

palate

prevalence

0%;

cleft

trunkus

left

Cleft

and

X-linked

overall

prevalence

alone

Disease.

12.5%;

lip

The submucous palate

Persistent

The

Heart

inheritance;

recessive

syndrome

Congenital

cava

Autosomal

with

sequence

vena

* * Syndrome

syndrome*

palate syndrome*

syndrome*

syndrome superior

sequence

Associated

syndrome*

inheritance;

left

syndrome*

and/or

association

syndrome* association syndrome*

syndrome*

Robin

Chapelle

Dilantin

lip

dominant Bixler

Charge Cleft

De Eastman

Syndromes

Fetal Hay-Wells Lowry-MacLean Lowry-Miller

Majewski Pierre

Miller Persistent

Saldino-Noonan

VATER Wallace

Autosomal

= Anomaly

TABLE

Pashayan, CLEFT LIP AND/OR PALATE 81

[

‘

et et

et Y

Ref.

H. H.

Kempen

1982 1975 1975

1977 1971

1975 1974 1975 1974 1971

1975 1974

Smith

Aurias

Nakagome Harris Sedano

Sanchez Sedano

Vogel

Allerdine

1975 Norwood Wright Van

Allderdine

tag.

and

ribs,

nose.

heart

nasal

placed

absent

fistula,

Narrow

skin

palpebral

flat

fingers

Small

cryptorchid-

pairs

neck.

Anal

abnormalities..

defect

antimongoloid

displaced

cryptorchidism,

proximal

Congenital

slant

Broad

nostrils,

involuted

Short

rectovaginal

heart

defects,

Eleven

labia.

Renal

foot.

glabella,

ears.

heart

hypertelorism.

table.

anomalies,

atresia,

disease,

Club

set

disease.

anteverted

micrognathia,

Nystagmus.

Prominent

Congenital

low

anal

excavatum.

Camptodactyly,

antimongoloid

renal

heart

Ocular

prominent another

nose,

and in

congenital

ears.

neck.

dysplasia.

bridge,

varus,

pectus

disease,

short

fissures.

pes

Strabismus.

Short

congenital

nasal

cupped

described

Congenital

heart

microcephaly.

hypertelorism,

Malformed

hypertelorism,

Acetabular

flat

lip.

anomalies.

fissures,

been

micrognathia,

fissures.

mouth.

Abnormalities.

fingers,

palpebral

Simple,

has

ears,

ocular

lower

Kyphoscoliosis, ocular

micrognathia,

skeletal

Large

congenital

mouth,

Small

face,

palpebral

tapered

deficiency.

palpebral

Micrognathia,

ears,

Myopia.

Syndrome

pointed

Micrognathia.

and

malformations.

Retracted

elbows,

tip.

round

ears.

growth

Chromosomal

slant

nose.

fontanel.

the

long Manifestation

slant

microcephaly, tract

microtic

equinovarus,

malformations.

downturned

hypertelorism.

and

bulbous

and

beaked

inheritance;

Clinical

renal

Lip

hypertelorism,

talipes

Urinary

malformed

set

deficiency,

mongoloid

Micrognathia.

Ocular

with

hypotonia,

Microcephaly,

philtrum,

extension

and

set,

low

Large,

Wide

micrognathia,

Cleft

X-linked ears,

nose

nose.

Antimongoloid

hernia,

Ocular

mental

short

Low

agenesis.

set

face.

Heart

hair.

ears,

flat

infancy.

Seizures, forehead.

low

without Renal

bossing.

limitation

X-linked

dimple,

Fuzzy

ears.

Broad High

umbilical

cry

Prominent

hypertelorism,

deficiency.

patterns.

Wrinkled

set

sacrum.

prominent

micrognathia,

retardation.

Frontal

forehead,

with dimple,

low

the

ridge

bossing.

microphthalmia.

Cat-like

Ocular

nose,

inheritance;

Mental

Micropenis.

ears,

forehead.

deficiency.

and

preauricular

retardation.

lip.

scaral

set

hypertonia.

Palate

ptosis,

death.

dermal

omphalocele

Frontal

palate.

Distorted

Beaked

recessive

cleft

low

palate.

Hypotonia.

nipples.

Mental

psychomotor

Mental

dimpling

fissures,

defect,

Limb

Cleft

early cleft

joints

Prominent

cleft

Malformed

and

palate.

and/or

lobe.

spaced

heart

weight.

with

Autosomal

weight.

and

thrive,

Hypoplastic

and

and/or

and

strabismus,

deficiency.

palpebral

hypertelorism,

micrognathia,

lung

growth

tongue.

Wide

hypotonia.

lip

palate

lip

birth

hypospadias,

Ocular Low defects.

cryptorchidism. thumbs. absent Low toes.

Mental Axial Brachycephaly. Hyperextensible Cleft fissures, chest. Large

ism,

Severe Cleft Congenital Cleft

slant Microbrachycephaly.

thymus.

Cleft

failure Cleft

bridge,

Associated

inheritance;

dominant Syndromes 7q+ 7q-

3p-

3p+ 4p-

3p+

10+

10.

10q+

11qgt+

10p+ llp+

11q

Involved

Chromosome

Autosomal =

Trisomy

AD TABLE

82 Cleft Palate Journal, January 1983, Vol. 20 No. 1

W. J.

Ref.

D. D.

1982

1966

1975 1982

1982

Smith Smith 1982

Reisman

1971 Penchazzadeh

Smith Smith

1971 1974

Smith

1966 1972

Orbeli Escober

Obeli

Short

Warkany

live

cleft

nasal

fole.

anus.

heart

ocular

Small,

crease.

beaked

fingers.

Failure

nuclear

occiput,

Clenched

synostosis.

coloboma,

degrees

abduction.

anomalies. dorsiflexed

mild

carp-shaped

and/or

folds.

Only

Long,

spells-severe

Thrombocyto-

Simian

prominence

iris

slender

hip

lip

Prominent

Epicanthic

congenital

Short

age.

Imperforate

genital

varying

Prominent

frequency

Long,

anthelix,

Cleft

Apneic

Radioulnar

nails.

limited

stenosis.

colobomas,

Posterior

Cryptorchidism.

Micrognathia. Epicanthic

with

fissures.

defect,

asymmetry.

thumbs.

months

feet.

Clinodactyly.

pelvis,

hernia.

Increased

Pyloric

pattern.

spots.

choroid heart

hypertelorism.

defect

dysplasia.

palate.

two prominent

retardation.

microphthalmia,

cryptorchidism,

and

Strabismus.

by palpebral

and

Small

EEG

Hypoplasia

type

eyes,

uterus.

pits.

Micrognathia.

Cryptorchidism. Ocular

Hypoplastic

die

Craniofacial

retinal

Iris

hands

umbilical

narrow

mental

set

congenital

Brushfield

and

coloboma.

50% iris,

ears.

hernia.

deficiency,

Hypospadias.

Brachydactyly.

testis.

pattern.

deep

hypospadias,

fissures. slanting

foot,