Handbook of Genetic Counseling/Cleft Lip and Palate

Cleft Lip and Palate

Review Medical History

(fill out remainder of intake and verify info)

Family History

(verify pedigree if we have one in his mother's chart or make a new one)

• Be sure to include:
  • cleft lip and palate
  • heart defects
  • birth defects
  • learning difficulties
  • intellectual disability
  • miscarriages
  • early deaths
  • consanguinity

Inheritance and Recurrence Risk

• If neither parent has a cleft than the inheritance is probably either multifactorial or recessive and these are not distinguishable usually
• multifactorial -- combination of genes and environment
• approximately 3-5% chance of having another similarly affected child this is 20-35 fold increase over baseline
• (this risk increases more if the couple have more than one affected child)

Multifactorial Risks of Cleft Lip/Palate

Relationship to index case	Cleft lip/palate	Cleft palate
Siblings (overall risk)	4%	1.8%
Siblings (no other affected)	2.2%	-
Siblings (2 affected siblings)	10%	8%
Siblings & affected parents	10%	-
Children	4.3%	6.2%
Second degree relatives	0.6%	-
Third degree relatives	0.3%	-
General population	0.1%	0.04%

• recurrence also influenced by how severe the cleft is 5.6% for bilateral lip/palate, 4.1% for unilateral lip/palate and 2.6% for cleft lip without cleft palate
• if it can be established that there are no other affected relatives, the risk to siblings (2.2%) is less than the overall risk (4%).
• The higher figure should be used if the history is unreliable or unavailable.
• If there is a third first degree relative than autosomal dominant or recessive inheritance should be considered.
• recessive inheritance
  • both parents contribute the same recessive gene to affected child
  • recurrence risk 25% or 1:4
  • gene not mapped
• Autosomal dominant -THIS IS WHAT WAS COUNSELED FOR THIS FAMILY
  • usually one parent will also have cleft
  • risk of recurrence is 50% or 1:2
  • gene mapped to short arm chromosome 6
  • X-linked recessive
  • pattern seen sometimes with clefting of the secondary palate or bifid uvula
  • x-linked recurrence risks
  • in one of these families from Iceland the single gene has been mapped to the long arm of chromosome X
• Association with a syndrome or collection of physical findings which run together in the same person, and for the most part are seen in all individuals who have that syndrome
  • Syndromes are more common in cleft palate alone than in cleft lip with or without cleft palate, but can occur in any of these
  • Syndromic clefts are commonly inherited as single gene defects, but they can be due to changes in the baby's chromosomes, something used during pregnancy or a sporadic change

Prevalence of Clefts

• 1:700 live births over 5,000 in US each year
• between 1/5000 and 1/1000 for cleft lip and/or cleft palate, and about 1/2500 for cleft palate alone
• more common among Asians 1: 500 and certain groups of American Indians 1:300 than among Caucasians 1:800
• occur less frequently among African-Americans 1: 2000
• Cleft lip and cleft palate together are more common in boys 3:2 ratio

Cleft Repair

• cleft lip-- usually be repaired in the first few months of life-- for most infants with cleft lip alone, the abnormality can be repaired within the first several months of life (usually when the baby is 10 to 12 pounds)
• cleft palate repairs are usually done between the ages of 9 and 18 months, but before the age of 2
• exact timing of these repairs depends on the baby's health and considerations of his or her future development and will be decided by surgeon

Other Possible Complications

Feeding Problems

• Feeding difficulties occur more with cleft palate abnormalities
• some babies with clefts have very few or no problems feeding
• others have more difficulty --the infant may be unable to suck properly because the roof of the mouth is not formed completelely
• breastfeeding is possible, but the use of special bottles and careful positioning of the baby are sometimes helpful modifications-- there are many types of bottles and nipples on the market that can assist with feeding an infant with cleft palate
• Dr. Doktour recommended Haberman Feeder®
• This is a specially designed bottle system with a valve to help control the air the baby drinks and to prevent milk from going back into the bottle

Hearing

• important for ears and hearing to be examined on a regular basis because children with cleft palate are more susceptible to ear infections (otitis media) than children without clefts
• Ear infections are often due to a dysfunction of the tube that connects the middle ear and the throat
• Children with many ear infections are at risk for hearing loss, language delays, and speech problems because they are not able to hear language normally when fluid collects in the middle ear.

Teeth Considerations

• only cleft lip-- teeth will probably not be affected
• if affects the gums where the teeth grow - teeth may not erupt normally and probably need dental/ orthodontic treatments

Speech Difficulties

• only lip --speech problems are unlikely
• cleft palate over half need speech therapy at some point in childhood
• many children who are born with a cleft palate develop normal speech by the age of 5
• delay in both the onset of speech and the development of speech sounds during the first 9-24 months of age is not unusual
• important to remember that some children, with or without a cleft palate, may simply develop speech more slowly than others.
• important to talk to your child and to encourage your child to talk to you
• before palate repair
  • there is no separation between the nasal cavity and the mouth and it can be difficult to learn how to make some sounds because the child cannot build up air pressure in the mouth because air escapes out of the nose and/or there is less tissue on the roof of the mouth for the tongue to touch
• After palate repair
  • your child may be able to learn more consonant sounds and say more words
  • speech may still be delayed during the early years
  • articulation problems (difficulties in making certain sounds) may persist in some children throughout early childhood for a variety of reasons.
  • if teeth do not "line up" correctly, speech may be understandable, but some sounds (like "s" or "sh") may sound distorted or "mushy."
  • VPI (velopharyngeal insufficiency or inadequacy)
  • when speech is produced correctly, the soft palate lifts and moves toward the back of the throat, separating the nasal cavity from the mouth so that air and sound can be directed out of the mouth.
  • inability to close off the nasal cavity from the mouth is called velopharyngeal inadequacy.
  • characterized by hyponasal speech "talking through their noses."
  • occurs because when the soft palate cannot close off the nose from the mouth, air and sound can escape through the nose during speech
  • Approximately 25% of children with repaired cleft palates still show signs of velopharyngeal inadequacy.
  • grunt or growl sounds may be behavior that some children learn in an attempt to compensate for velopharyngeal inadequacy-- although it can be corrected by speech therapy it should be discouraged
  • Children with velopharyngeal inadequacy may also have a voice disorder.
  • voice may sound hoarse or "breathy" and may fatigue easily and is usually caused by the strain that he or she puts on the vocal cords while trying to build the pressure necessary for normal speech.
  • Speech therapy alone may be able to correct your child's speech disorder. Therapy can be extremely effective for children with mild hypernasality, an articulation disorder, or speech delay.
  • Speech therapy alone will generally NOT correct hypernasality that is caused by moderate to severe velopharyngeal inadequacy.
  • may require another palate surgery to help with speech
  • surgery is the most frequently-chosen approach for improving velopharyngeal function, but a prosthetic device may be an option for some patients.

Learning Difficulties

• none expected it isolated cleft lip and palate
• if part of a cluster of a syndrome learning ability is sometimes affected

Psychosocial Assessment

• Having a baby can be pretty stressful especially when there are complications. How are you handling it?
• Do you have help from your family?
• Have you explained any of this to your friends or family?
• Is the father of the baby involved in any way?
• How is that?
• Are you attending school?
• Working?
• The surgeries and treatment can get pretty expensive do you have health insurance coverage?
• Other financial assistance?

Financial Assistance

• Health insurance will pay for all or part of the necessary care
• may qualify for BCMH
• would probably qualify for WIC

Psychosocial Concerns

• Initial shock and adjustment for the family
• Often a period of mourning the anticipated child and the situation
• Possibility of mother interacting differently and interacting less with infants with anomalies
• Guilt - nothing you could have done to prevent or cause this
• Feelings of concern, anxiety, and grief are not unusual
• mothers of babies with clefts report more stress and more concerns about their competence as parents than mothers of healthy babies
• reproductive plans generally unaltered by birth of child with cleft
• later challenges as the child grows

References

• Kummer, A.W. Cleft Palate and Craniofacial Anomalies Effects of Speech and Resonance. 2001. Thomson Learning Inc.
• [1]
• [2]
• [3]
• [4]

Patient Resources

see attached

Differential Diagnosis

• Van der Woude Syndrome
• among most common syndromic causes of CL/P may be responsible

for up to 3%

• AD disorder gene mapped to long arm chromosome 1
• presence of pits of the lower lip and cleft lip, cleft palate,

or both

• may also have neonatal teeth and missing teeth
• development usually normal speech difficulties related to

cleft palate

Cleft Related Genetic Syndromes/Diseases

The following table was extracted from a table on Embryogenesis by Dr. Harold C. Slavkin; Director, National Institute of Dental & Craniofacial Research (NIDCR)

TYPE (1)	GENE NAME	GENE SYMBOL	CHROMOSOMAL LOCATION	OMIM NUMBER FOR GENE	SYNDROME	OMIM NUMBER FOR SYNDROME	INHERITANCE (2)	DESCRIPTION OF CRANIOFACIAL FEATURES (3)
ECM	Collagen, type XI, alpha-2 chain	COL11A2	6p21.3	120290	Stickler syndrome, type II	184840	AD	cleft palate, micrognathia, glossoptosis, severe myopia, flat facies, dental anomalies, deafness
					Osmed syndrome	215150	AR	saddle nose, cleft palate, progressive deafness
					Shprintzen-Goldberg syndrome	182212	AD	craniosynostosis, microcephaly, maxillary and mandibular hypoplasia, palatal shelf soft tissue hypertrophy, cleft palate, prominent nose, narrow palpebral fissures
ECM	Glypican-3	GPC3	Xq26	300037	Simpson dysmorphia syndrome	312870	X	disproportionately large head, coarse facies, large protruding jaw, wide nasal bridge, upturned nasal tip, large mouth, thickened lips, central cleft of lower lip, midline groove of tongue and inferior alveolar ridge, enlarged tongue, short neck
ENZ	Phenylalanine hydroxylase	PAH	12q24.1	261600	Phenylketonuria	261600	AR	microcephaly, occasional cleft palate, long simple philtrum, thin upper lip, flattened nasal bridge, epicanthus, upturned nose
IS	Retinoblastoma-1	RB1	13q14.1-q14.2	180200	Retinoblastoma	180200	AD	cleft palate, high forehead, prominent eyebrows, broad nasal bridge, bulbous tip of the nose, large mouth with thin upper lip, long philtrum, prominent earlobes
SEC	Sonic hedgehog	SHH	7q36	600725	Holoprosencephaly, type 3	142945	AD	cyclopia, ocular hypotelorism, proboscis, midface hypoplasia, single nostril, midline cleft upper lip, premaxillary agenesis
TM	Fibroblast growth factor receptor-2	FGFR2	10q26	176943	Crouzon craniofacial dysostosis	123500	AD	craniosynostosis, parrot-beaked nose, short upper lip, hypoplastic maxilla, relative mandibular prognathism, shallow orbit
					Jackson-Weiss syndrome	123150	AD	craniosynostosis, midfacial hypoplasia
					Apert syndrome	101200	AD	craniosynostosis, brachysphenocephalic acrocephaly, flat facies, high narrow palate
					Pfeiffer syndrome	101600	AD	mild craniosynostosis, flat facies, acrocephaly
					Beare-Stevenson cutis gyrata syndrome	123790	AD	craniosynostosis, cloverleaf skull, cleft palate or uvula, craniofacial anomalies
TM	Peroxisomal membrane protein-3	PXMP3	8q21.1	170993	Zellweger syndrome-3	170993	AD	high forehead, dolichoturricephaly, large fontanels, flat face, round face, hypoplastic supraorbital ridge, epicanthus, cleft palate
TM	Diastrophic dysplasia sulfate transporter	DTDST	5q32-q33.1	222600	Diastrophic dysplasia	222600	AR	hypertrophic auricular cartilage, cleft palate, micrognathia
					Neonatal osseous dysplasia I	256050	AR	micrognathia, cleft palate, flat nasal bridge, mid-face hypoplasia, neonatal osseous dysplasia, lethal chondrodysplasia
TM	Patched	PTC	9q22.3	601309	Basal cell nevus syndrome (Gorlin syndrome)	109400	AD	macrocephaly, broad facies, frontal and biparietal bossing, mild mandibular prognathism, odontogenic keratocysts of jaws, misshapen and/or carious teeth, cleft lip and palate, ectopic calcification of falx cerebri
TF	Microphthalmia-associated transcription factor	MITF	3p14.1-p12.3	156845	Waardenburg syndrome, type IIA	193510	AD	wide nasal bridge, short philtrum, cleft lip or palate, deafness
					Pallister-Hall syndrome	146510	AD	short nose, flat nasal bridge, multiple buccal frenula, microglossia, micrognathia, cleft palate, malformed ears
TF	Paired box homeotic gene-3	PAX3	2q35	193500	Waardenburg syndrome, type I	193500	AD	wide nasal bridge, short philtrum, cleft lip or palate, occasional deafness, dystopia canthorum
TF	Sry (sex-determining region Y)-box 9	SOX9	17q24.3-q25.1	211970	Campomelic dysplasia	211970	AR	small chondrocranium, large neurocranium, occasional platybasia, cleft palate, retroglossia, micrognathia, flat nasal bridge, malformed ears
TF	Twist	TWIST	7p21	601622	Saethre-Chotzen syndrome	101400	AD	craniosynostosis, acrocephaly, brachycephaly, flat facies, thin long pointed nose, cleft palate, cranial asymmetry, ptosis, malformed ears
UNK	DiGeorge syndrome chromosome region	CATCH22	22q11	188400	DiGeorge syndrome	188400	AD	low-set ears, short ears, small mouth, submucous or overt palatal cleft, cleft lip, bulbous nose, square nasal tip, short philtrum, micrognathia,
					Velocardiofacial syndrome	192430	AD	Pierre Robin syndrome, cleft palate, small open mouth, myopathic facies, retrognathia, prominent nose with squared-off nasal tip
UNK	Treacle	TCOF1	5q32-q33.1	154500	Treacher Collins mandibulofacial dysostosis	154500	AD	malar hypoplasia, cleft palate, mandibular hypoplasia, macrostomia, malformed ears, sensorineural deafness, coloboma of lower eyelid

Notes

1. CS; cytoskeletal protein, ECM; extracellular matrix protein; ENZ; enzyme, IS, intracellular signalling protein, NP; nuclear protein, SEC; secretory protein, TM; transmembrane protein, TF; transcription factor, UNK; unknown
2. AD; autosomal dominant, AR; autosomal recessive, X; X-linked, XD; X-linked dominant, XR; X-linked recessive
3. The following description is only a summary of the craniofacial features of the diseases and disorders. For detail information regarding defects in other affected tissues and organs, refer to the Online Mendelian Inheritance in Man (OMIM) at [5]

• [6]
• The information in this outline was last updated 2002.