Dysmorphology assessment in neonates

• The following focuses on the examination for dysmorphic features in a baby.
• A thorough examination of all systems is vital when considering a syndrome diagnosis.
• Initial observation will enable assessment of general muscle tone, movements, postural abnormalities and abnormal body proportions.

Growth

Assess whether the baby's growth parameters are in proportion as well as the percentiles:

• birthweight
• length
• head circumference.

Ectodermal features

Examine the skin and hair:

• skin
  • texture
  • colour
  • birthmarks
  • redundancy
  • defects
• hair
  • scalp hair
  • body hair
  • colour
  • distribution
  • position of anterior and posterior scalp hairline.

Skull

Examine the skull:

• shape
• symmetry
• sutures (over-riding/normal/widely open)
• fontanelle size and number.

Face overall impression

In examining the face, it can be useful to first gain an overall impression of the facial appearance. Sometime, an overall gestalt can be diagnostic (for example, Down syndrome).

If no diagnosis is made it is important to divide the face into sections to examine it thoroughly.

You may divide the face into the forehead, midface and oral region. It can sometimes help to cover parts of the face with your hand, in order to isolate the section of the face you are assessing.

In assessing the face, it is important to view the face from the front and from the lateral view. The depth or height of structures such as the nasal bridge, the position of the mandible relative to the maxilla and the development of the midface are best assessed by the lateral view.

Examination needs to be considered in the context of family features so it is useful to see parents and any siblings.

Face shape

Examine the overall face shape, symmetry and facial muscle movement:

Forehead region

When examining the forehead assess:

• forehead shape - (broad/bitemporal narrowing/tall)
• eyes
  • palpebral fissure length (short/long)
  • palpebral fissure slant (up/down)
  • epicanthic folds - a fold of skin which arcs from below the eye into the upper lid
  • eye spacing (use a rough guide of 1:1:1 for the ratio of left palpebral fissure length: inner canthal distance: right palpebral fissure length)
  • palpebral fissure shape
  • red reflex
  • iris colour
  • pupil shape
  • retina
  • globe position (assessed from lateral view: protuberant vs deep set globes).

Midfacial region

When examining the midfacial region assess:

• nose - divide the nose into three sections from the lateral view from superior to inferior into the nasal root, bridge and tip:
  • root
  • bridge (depressed/prominent/broad)
  • tip 
  • columella (the vertical ridge separating the nostrils)
  • nostrils - patency, position (anteverted nostrils often reflect a short nose)
• ears - ear rotation is normally 15 degrees posterior to the vertical plane of the head
  • ear shape and structure
  • ear position.

Oral region

When examining the oral region of the face note:

• mouth size and shape
• lip shape, thickness
• gum thickness
• philtrum definition and length
• jaw position (prognathia/micrognathia)
• palate shape
• oral cavity - natal teeth/frenulum/tongue size and morphology.

Hands and feet

Examine hands and feet carefully:

• overall shape and size of hand and foot
• digit number
• digit shape (for example, clinodactyly) and length
• webbing between digits
• palmar, plantar and digit creases
• nail morphology.

Joints and skeleton

Examine joints and skeleton for:

• contractures
• limb shortening
• joint range of movement
• soft tissue webbing across joints (pterygium)
• sternum length and shape (pectus carinatum / pectus excavatum)
• shape of thoracic cage
• spine length, straight/curved
• neck length, webbing.

Genitalia and anus

Check the following:

• phallus size, morphology
• development of scrotum and palpation of testes
• development of labia
• position of anus relative to genitalia
• patency of anus
• note any genital ambiguity.

Examine family members

Examination of other family members (siblings and parents) may be crucial to determine whether any dysmorphic features noted are familial or syndromic.

In cases where the history and clinical features suggest a specific diagnosis, it may be possible to order a confirmatory test.

Tests and examinations to use in the syndrome work-up include:

• renal ultrasound
• echocardiogram
• cranial ultrasound
• MRI
• midline abnormalities tend to cluster together, so, for example, an echo may be indicated when there is a cleft palate and dysmorphic features
• eye examinations are useful for clues to make a syndrome diagnosis
• skeletal radiographs are indicated when there is disproportionate short stature or other abnormalities in the skeletal system
• x-rays may be useful to diagnose a skeletal dysplasia, a disorder caused by a primary abnormality of bone growth/development, or to assist in diagnosing a dysmorphic syndrome which can have skeletal abnormalities associated with it.

Genetic skeletal survey

A genetic skeletal survey includes:

• AP and lateral X rays of the skull
• AP and lateral pelvis and spine (cervical to sacrum)
• AP of one arm
• AP both hands
• AP of one leg and AP of both feet.

In a neonate, it may be sufficient to obtain a ‘baby-gram’ (x-ray of the baby) and a separate x-ray of the hands and feet.

Pathology

• Routine haematology and biochemistry
• Blood chromosomes are indicated when:
  • there are multiple congenital abnormalities +/- dysmorphic features
  • there is one congenital abnormality in the presence of dysmorphic features and/or growth restriction.

Chromosome abnormalities are more likely when there are abnormalities of growth, most commonly growth restriction and microcephaly, in association with dysmorphic features and congenital abnormalities.

Chromosome analysis issues to note

• A normal chromosome analysis does not exclude a single gene mutation or a micro deletion syndrome.
• A normal antenatal chromosome analysis does not completely exclude a chromosome abnormality as the resolution of chromosome banding may be greater on a postnatal sample than samples from chorionic villus sampling (CVS) or amniocentesis.
• If a chromosome abnormality is strongly suspected it is indicated to repeat chromosomes in the postnatal period.
• A chromosome test takes a minimum of five days and the time taken to obtain a result depends on the growth of cells in culture.
• If an infant has been transfused, there is a small risk that there may be circulating lymphocytes from the blood donor which may lead to an ambiguous result.
• Most laboratories recommend delaying a karyotype until one week following a transfusion.

Flourescence in situ hybridation (FISH)

• For trisomies 13/18/21, FISH is used to expedite diagnosis when trisomy of a specific chromosome is suspected.
• A result is usually available within 48 hours.
• FISH for submicroscopic deletion syndromes are tests using a probe that detects small chromosome deletions not visible on routine chromosome analysis.
  • 22 q FISH should be considered in babies with heart defects, particularly those with cleft palate and dysmorphic features.
  • The commonest cardiac defects seen are conotruncal (abnormalities of cardiac outflow tracts) heart defects and VSD.
  • 7 q FISH (Williams' syndrome) should be considered in babies with supravalvular aortic stenosis and/or hypercalcaemia.

Fragile X testing

Fragile X testing is rarely indicated in the neonatal period in the absence of a family history.

Single gene tests

Single gene tests may be indicated, depending on the syndrome being considered. Such tests usually require liaison with the clinical geneticist.

Microarray

Chromosome Microarray (molecular karyotype) is a detailed genetic test that looks for extra or missing segments of DNA in the chromosomes. The result are available in 10-14 days.

Saliva can be used as an alternative to blood for microarray testing - simple, quick and painless

Further information is available on the Victorian Clinical Genetics Services (VCGS) website.

Biochemical tests

Biochemical tests such as 7-dehdrocholesterol assays if considering Smith-Lemli-Opitz as a diagnosis.

It can be awkward to raise a concern that a child is dysmorphic. However, it is important to communicate concerns to the family in order to assist them to understand the reasons behind investigations, examinations of other family members, and referrals to genetics.

Remember:

• Withholding concerns regarding dysmorphism can be bewildering and frightening to parents.
• One useful tactic is to ask the parents whom the child resembles in the family.
• The family may then disclose their concerns regarding the child's appearance and this can then be a topic for careful discussion.
• Geneticists often explain that the reason for examining the baby's appearance is to look for clues as to the cause of the problem(s) seen in the baby.
• Feedback from families suggests that it is best to avoid terms such as dysmorphic, and to use terms such as ‘distinctive facial features’ instead.
• Families report that the terms abnormal or deformed can be offensive, and that an abnormality is better described as a problem or difficulty.
• Parents need to be provided with good information about the condition and informed about sources of further information and support.

Consumer

Better Health Channel - Birth defects

References

Aase, JM. Diagnostic dysmorphology Plenum Medical Book Company, New York, 1990