Dysmorphia

## Dysmorphology

**Dysmorphology:** the evaluation, diagnosis and study of birth defects or birth defect syndromes

**Etiology of Dysmorphia:** teratogenic, genetic, multifactorial, etc.

**Major** **Birth Defect:** a defect present at birth which has cosmetic, medical, or surgical significance

**Types**

* Malformation = primary defect arising from poor formation of tissue
* Disruption = secondary defect caused by breakdown of normal tissue
* Deformation = secondary defect caused by external forces on normal tissue
* Dysplasia = primary defect due to abnormal cellular organization within a specific tissue
* Syndrome = pattern of abnormalities which occur together from a single cause
* Sequence = series of defects secondary to a single localized abnormality in early development
* Complex = abnormalities of different structures which arose in the same embryonic region
* Association = nonrandom occurrence in two or more individuals of multiple, idiopathic anomalies of blastogenesis

**Minor Anomalies**

* <4% of population
* no medical, cosmetic, nor surgical significance

* *Associated Risk of Major Malformation*
	+ 1 minor anomaly = 3.7% risk of MM
	+ 2 minor anomalies = 6.7% risk of MM
	+ 3 minor anomalies = 19.6% risk of MM

**Frequency of Birth Defects**

* ~2% of newborns
* ~4% of toddlers
* 6-8% of school-age

**Birth Defect Associations**

* Low Birth Weight
	+ <1500 gm = 16.2% risk of BD
	+ 1500-1900gm = 13.2% risk of BD
	+ >4000gm = 2.8% risk of BD

* Twinning
* Males > Females
* Consanguinity

**Dysmorphology Evaluation**

* Medical History
	+ Pregnancy: exposures, obstetric issues, prenatal testing
	+ Delivery/Newborn Period: type of delivery, birth stats, complications, feeding
	+ Infancy/Childhood: growth and development, hospitalizations, surgeries, illness, lab data
* Family History
	+ Siblings, parents, consanguinity, ethnicity; recurrent miscarriages, stillborns, neonatal deaths; birth defects
	+ Negative Family History does *not* negate risk of genetic cause
	+ Presence of similarly affected males relatives of a male child suggests X-Linked Inheritance
	+ Similar Features in parents/child = benign familial resemblance or undiagnosed parent
* Physical Examination
	+ Growth = use appropriate growth curves for gender, ethnicity, condition
	+ Note Major & Minor anomalies; normal variants
	+ Measurements = abnormal is >2 SD above or below the mean
		- Head: size, shape, symmetry, face size, shape, hairlines
		- Eyes: slant, size, placement, epicanthal folds, eye size, inner/outer canthal, interpupillary distance
		- Nose: length, bridge, nares, columella
		- Ears: shape, size, location, earlobe creases, preauricular pits / tags
		- Mouth: vermillion, shape, dentition, palate, uvula, lip pits
		- Philtrum: flat vs grooved, size
		- Chin: prognathia, micrognathia, retrognathia
		- Neck: length, webbing, lesions, thyromegaly, adenopathy, branchial cleft
		- Chest: symmetry, shape, size, heart
		- Skin/Hair: skin pigmentation, skin lesions, hair distribution, hair pigmentation
		- Extremities: symmetry, size, fingers, palms, toes, soles, flat/arched
* Assessment
	+ Compare to other relatives
	+ Certain anomalies have better predictive value
	+ Concentrate on most unusual feature
* Laboratory Evaluation
	+ Blood, Skin, Buccal Cells
		- Karyotype
			* trisomies
			* mosaicism
		- Microarray (CGH)
			* particular pattern of anomalies
			* ambiguous genitalia
			* developmental delay +/- major/minor anomalies
			* child with 2 single gene disorders
			* history of recurrent miscarriages
		- FISH/MLPA
			* testing for specific disorders
		- DNA Testing
			* Single gene disorder
			* Fragile X
			* Uniparental Disomy
			* X-inactivation
			* Methylation Studies
			* Whole Exome Testing
		- Metabolic Studies
			* amino acids, organic acids, lactate, pyruvate, ammonia, glucose
			* testing only if metabolic disorder suspected
		- Radiography
			* delineation of particular skeletal dysplasia
			* determine bone age
				+ delayed = hypopituitarism
				+ advanced = overgrowth syndromes
		- Ophthalmology Evaluation
			* Corneal Clouding? Iris Anomalies? Retinal Abnormalities? Visual Acuity?
		- Biopsies
			* Skin = ultrastructural analysis, inclusions, collagen studies
			* Nerve = inclusions
			* Muscle = ultrastructural analysis, mitochondria
			* Liver = ultrastructural analysis, mitochondria

* Follow-Up/Counseling/Management
	+ Diagnosis may become apparent with age
	+ Natural history of disease with appropriate screening
	+ Counseling about genetics, recurrence, prognosis
	+ Prenatal diagnosis options
	+ Treatment, if any

## List of Dysmorphic Features

* micrognathia
* cleft lip & palate
* broad toes
* ptosis
* craniosynostosis
	+ scaphocephaly/dolichocephaly
	+ trigonocephaly
	+ turricephaly
	+ brachycephaly

* upslanted eyes
* downslanted eyes
* blepharophimosis
* hypertelorism
* hypotelorism
* microcephaly
* macrocephaly
* micropthalmia
* microstomia
* macroglossia
* thin vermillion border
* preauricular tags, pits
* flat philtrum
* rectangular nose
* bulbous nose
* small ears
* low-set ears
* long palpebral fissures
* bifid uvula
* velopharyngeal insufficiency
* retrognathia
* prognathia
* midface hypoplasia
* small nose
* flat nasal bridge
* neck webbing
* pectus carinatum
* pectus excavatum
* cafe-au-lait spots
* pigmented nevi
* temporal balding
* hypertrichosis
* hemihypertrophy
* brachydactyly
* clinodactyly
* arachnodactyly
* polydactyly
* syndactyly
* pes planus
* pes cavum
* sandal foot
* rocker-bottom feet
* single palmar crease (Simian crease)
* malformed ears
* branchial cleft
* lip pits
* palmar pits
* hypoplastic nails
* earlobe creases
* round face
* long face
* bifid ribs
* shield chest
* bell-shaped chest
* prominent glabella
* short stature
* tall stature
* gynecomastia
* male with female body habitus
* cryptorchidism
* macroorchidism
* triangular face
* shortened proximal limbs
* absent muscle
* prominent lips
* periorbital fullness
* brushfield spots
* stellate irides
* ambiguous genitalia
* tapered fingers
* hypogonadism

## Syndromes/Conditions With Generalized Dysmorphia

* Tetrasomy 12p
* Ring X Syndrome
* Maternal UPD14
* Brancho-oculo-facial Syndrome
* Coffin-Lowry Syndrome