Linda Ikuta, MN, RN, CCNS, PHN, and Ksenia Zukowsky, PhD, APRN, NNP-BC ❍ Section Editors

❍ Section Editor

Clinical Issues in Neonatal Care

Important Considerations in the

Initial Clinical Evaluation of the
Dysmorphic Neonate
Patroula Smpokou, MD; Brendan C. Lanpher, MD; Kenneth N. Rosenbaum, MD

ABSTRACT
Background: The approach to clinical evaluation of the dysmorphic neonate can be challenging and multifaceted. It
requires specialized knowledge of rare diagnoses and awareness of immediate versus long-term needs for the newborn
and the family.
Purpose: This review summarizes important considerations in the initial evaluation of genetic syndromes, which can
present in the neonatal period with variable aspects of dysmorphism.
Methods:  An overview of the literature in this area is provided.
Findings/Results:  Several overlapping areas of concern for working with this population are addressed, including com-
munication with the family, fundamentals of the physical examination, common genetic disorders, syndromes, as well as
palliative care and end of life decision making for the newborn in the context of family needs.
Implications for Practice: The initial approach for the neonatal practitioner needs to focus on various aspects of the
newborn's care, including medical stabilization, determining whether immediate laboratory or imaging studies are
needed, careful physical examination with particular attention to detail, appropriate and timely communication with the
family, and knowledge of various specific aspects of rare diseases.
Implications for Research:  More research is needed to better understand how to best support the newborn born with
dysmorphia or a rare disease. Particular attention needs to be focused on strategies to best support the family who is
often in crisis during the neonatal period.
Key Words:  dysmorphism, dysmorphic features, dysmorphic neonate, genetic evaluation, genetic syndrome

T
he clinical genetic evaluation of a neonate sus- from a potential genetic diagnosis and related
pected of having an underlying syndromic testing.1,2 Moreover, the critical aspects of an initial
diagnosis can be complex, multifaceted, and assessment for life-threatening complications that
emotionally burdensome to the family. In the neona- need immediate attention and treatment need to be
tal nursery or intensive care setting, the initial addressed. And most importantly careful and sensi-
approach is extremely important. Many consider- tive ways of communicating those concerns to the
ations must be addressed when contacting specialists family are vital to the care of these infants in the
for consultations and communicating specific con- context of families.
cerns to the family. This review presents a practical approach and
Fundamental to this initial approach (for all neo- important considerations in the initial evaluation of
natal practitioners—nurses, nurse practitioners, a neonate with possible dysmorphia and suspected
physician assistants, and neonatologists) is a clear syndromic diagnosis from the perspective of the neo-
and well-rounded knowledge and appreciation for natal clinician.
the complexity of this evaluation, the correct
approach to assessing dysmorphia in the setting of a COMMUNICATING CONCERNS WITH
recent birthing process, and the uncertainties arising THE FAMILY
When a neonatal clinician encounters a possibly dys-
Author Affiliations: Division of Genetics & Metabolism, Children's morphic neonate, the first response is often self-
National Health System, Washington, DC (Drs Smpokou, Lanpher, and doubt. Assessing dysmorphism has subjective ele-
Rosenbaum); and Department of Pediatrics, The George Washington ments that are often triggered by clinical experience
School of Medicine & Health Sciences, Washington, DC (Drs Smpokou,
Lanpher, and Rosenbaum). and expertise. Key points in the initial communica-
The authors declare no conflicts of interest. tion with the family include the following:
Correspondence: Patroula Smpokou, MD, Division of Genetics &
Metabolism, Children's National Health System, 111 Michigan Ave NW,
1. First congratulate the family on the birth of the
Ste 1950, Washington, DC 20010 ([email protected]). baby. This is very important and tremendously
DOI: 10.1097/ANC.0000000000000216 appreciated by families. This is a very special

248 Advances in Neonatal Care • Vol. 15, No. 4 • pp. 248-252

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 Clinical Approach to the Dysmorphic Neonate 249

time for the family regardless of whether the arrives. Some families are not ready for this and
newborn ultimately has a genetic diagnosis. timing becomes important.
2. Point out the positives without being overly or 8. Treat the newborn like any other “typical” or
falsely reassuring. “normal” infant. Families are very sensitive to
3. Be honest about your concerns. Families appre- body language and word choice, which can
ciate honesty and the genuine honesty of the unintentionally reveal your underlying senti-
neonatal provider builds trust. ment about their newborn.
4. Do not mention specific diagnoses or syn- 9. Avoid separating the newborn from the par-
dromes by name initially unless there is a great ents, if at all possible. Most dysmorphic syn-
deal of confidence in the diagnosis. When any dromes do not pose an immediate threat to the
uncertainty exists, it is preferable to speak in newborn's health unless major malformations
general terms. Initial words used by neonatal are present that need close monitoring and/or
clinicians tend to stick in the parents’ minds management.
even if they ultimately are refuted.
5. Assess the educational and cognitive level of FUNDAMENTALS OF THE
the family and use words that make sense to DYSMORPHOLOGY EVALUATION
them. Scientific terms are rarely useful initially
and only create additional anxiety. Assessment for dysmorphology or dysmorphic cra-
6. Reassure the family that you will keep them niofacial features can be quite subjective and requires
informed and updated (and do so). expertise, experience, and attention to detail. The
7. Ask for their permission to have their newborn term “dysmorphic” implies the presence of abnor-
evaluated by a specialist, such as a clinical mal features as compared with what is considered
geneticist. The family must be informed about “normal.”2,3 To overcome some of the subjectivity in
this planned assessment before a geneticist this process, several more objective, clinical tools

TABLE 1.  Select Genetic Syndromes and Their Associated Clinical and Laboratory Phenotype
Characteristic Clinical/Laboratory
Genetic Syndrome Findings Laboratory Testing
Down syndrome CHD, hypotonia, organ malforma- Chromosome analysis, FISH
tions (eg, renal)
Edwards syndrome (trisomy 18) IUGR, CHD, short sternum, overlap- Chromosome analysis, FISH
ping fingers, hypertonia
Patau syndrome (Trisomy 13) CL/CP, CHD, brain malformations, Chromosome analysis, FISH
polydactyly
Turner syndrome (45,X) CHD (eg, aortic coarctation), Chromosome analysis, FISH
hydrops, lymphedema, webbed
neck, skeletal/renal malformations
22q11 deletion syndrome (Velocar- CHD (eg, TOF), CL/CP, hypotonia, Chromosome analysis, FISH, chro-
diofacial syndrome) hypocalcemia, immune deficiency mosome microarray
Noonan syndrome Macrosomia, CHD (eg, VSD, ASD, Gene sequencing
PVS), HCM, hydrops, lymphede-
ma, hypotonia, webbed neck
Neurofibromatosis type 1 Multiple CALS, hypotonia Gene sequencing
Williams syndrome CHD (eg, SVAS), hypotonia, failure Chromosome analysis, FISH, chro-
to thrive, hypercalcemia mosome microarray
Prader–Willi syndrome Severe hypotonia, hypogenitalism 15q11 methylation studies
(males), failure to thrive
Beckwith–Wiedemann syndrome Macrosomia, omphalocele, mac- 11q15 methylation studies
roglossia, hypoglycemia
Craniosynostosis syndromes Craniosynostosis (often coronal), Gene sequencing
(Pfeiffer, Apert, Crouzon syn- characteristic facial and/or ex-
dromes) tremity features
Abbreviations: ASD, atrial septal defect; CALS, café-au-lait spots; CHD, congenital heart disease; CL/CP, cleft lip/cleft palate; FISH,
fluorescence in situ hybridization; HCM, hypertrophic cardiomyopathy; IUGR, intrauterine growth restriction; PVS, pulmonary valve
stenosis; SVAS, supravalvular aortic stenosis; TOF, tetralogy of fallot; VSD, ventricular septal defect.

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 250 Smpokou et al

have been developed by experienced clinical dys- should be reassessed after these external influences
morphologists to assist in categorizing and system- have been resolved.1,2
atically organizing various facial characteristics. Owing to the dynamic nature and subjectivity
Charts to plot the length, distance, or rotation of inherent to the assessment of craniofacial features,
different physical characteristics and organs are photographs or videos sometimes are useful to docu-
published and utilized by clinical geneticists to ment these features for purposes of comparison or to
objectively categorize the physical assessments.3 The seek alternative opinions. With the family's permis-
distance between the eyes, the length and rotation of sion, neonatal practitioners, particularly those in
the ears, the length of the philtrum, the length of the more remote settings where clinical geneticists are
fingers, the palms or soles, the distance between the not readily available for in-person consultations,
nipples, or the chest circumference can all be accu- should consider this approach.4-7
rately measured and plotted on graphs against Documentation of assessment findings is critical.
empirically derived normal measurements.2,3 This In the current healthcare environment of work-hour
approach can be useful when a subjective assessment rules and frequent practitioner hand-offs, docu-
is in doubt or needs confirmation. menting all abnormal findings in the medical record
Appreciation of the dynamic nature of the dys- is the only practical way to achieve consistency.
morphology examination is essential. Craniofacial When describing craniofacial features that appear
features can change dramatically early in life. Edema “abnormal,” specific terms and anatomical land-
and mechanical pressure, for example, can distort or marks are employed to “paint a picture” without
alter the newborn's true facial features, resulting in actually drawing a picture.4 Such terms as down-
deformation of the face. A history of maternal uter- slanting palpebral fissures, telecanthus, hyper-
ine malformation, oligohydramnios, prenatal sub- telorism, wide nasal bridge, wide forehead, and low-
stance exposure, atypical in-utero positioning, or set ears are often used to describe findings.2,3
prematurity suggest that the newborn's features Documenting a detailed and systematic examination

TABLE 2.  Select Large Molecule Inherited Metabolic Disorders and Associated Clinical and
Laboratory Phenotypes
IMD Group Characteristic
(Examples) Typical Organ Malformations Biochemical Findings Typical Dysmorphism
Mitochondrial Brain, heart High lactate, pyruvate, High forehead, epicanthal
(PDHC defi- alanine, metabolic folds, short and upturned
ciency) acidosis nose, long philtrum
Sterol (SLOS, MA) Multiple organs (brain, cardiac, Low total cholesterol, Micrognathia, ocular ptosis,
kidneys, facial clefting, geni- elevated 7DHC (SLOS), short/upturned nose, 2-3
tal, extremity in SLOS); liver abnormal liver func- toe syndactyly (SLOS); high
disease, skin rash in MA tion, high urine meva- forehead, dolichocephaly,
lonic acid (MA) low-set ears, thin lips (MA)
Peroxisomal Hydrops, multiple organs Abnormal liver function, High forehead, large fonta-
(Zellweger syn- (brain, heart, kidneys, hear- abnormal VLCFA, bile nels, micrognathia, ear
drome) ing, retinopathy, cataracts, acids anomalies
liver disease, skeletal)
Lysosomal storage Hydrops, skeletal (dysostosis Abnormal liver function, Coarse face, short/upturned
(Hurler syn- multiplex, contractures), car- anemia, thrombocyto- nose, ear anomalies
drome) diac, ocular (corneal cloud- penia
ing), brain, organomegaly
(liver, spleen), hematologic
CDG Hydrops, multiple organs Abnormal liver function, Variable, abnormal “fat pads”
(brain, heart, kidneys, GI, coagulopathy, abnor-
hearing, retinopathy, liver mal immune function
disease, skeletal), organo-
megaly, skin
Copper transport Brain, skeletal, skin Low serum copper, Long/narrow face, bitemporal
(Menkes disease) ceruloplasmin narrowing, myopathic ex-
pression, cutis laxa, “kinky”/
hypopigmented hair
Abbreviations: CDG, congenital disorders of glycosylation; GI, gastrointestinal; IMD, inherited metabolic disorder; MA, mevalonic
aciduria; PDHC, pyruvate dehydrogenase complex; SLOS, Smith—Lemli–Opitz syndrome; VLCFA, very long-chain fatty acids.

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 Clinical Approach to the Dysmorphic Neonate 251

with attention to describing only what is observed RARE METABOLIC-DYSMORPHIC

(without interpretation) is encouraged.4,5 SYNDROMES
COMMON GENETIC DIAGNOSES AND Special consideration needs to be given to a group of
ASSOCIATIONS rare genetic disorders that affect the metabolism of
large molecules. In their most severe forms, these
In certain genetic conditions, recurrent associa- disorders can present in the neonatal period. To this
tions have emerged that can guide the initial evalu- group of dysmorphic-metabolic syndromes belong
ation and management of the neonate, even before certain mitochondrial disorders (eg, pyruvate dehy-
specialist consultation is available. For example, drogenase complex deficiency), sterol/cholesterol
some congenital heart defects are more often asso- pathway disorders (eg, Smith–Lemli–Opitz syn-
ciated with one syndrome than another. Certain drome and mevalonic aciduria), peroxisomal disor-
physical examination findings, such as severe ders (eg, Zellweger syndrome), lysosomal storage
hypotonia or hydrops fetalis, should trigger the disorders (eg, mucopolysaccharidoses), congenital
consideration of a different set of genetic diagno- disorders of glycosylation, and copper transport dis-
ses.4-7 Table 1 outlines some of the most common orders (eg, Menkes disease).6 Neonates with small
genetic syndromes and their associated clinical and molecule inherited metabolic disorders (IMDs), such
laboratory findings. as organic acidemias or urea cycle disorders,

Summary of Recommendations for Practice and Research

What we know: • The initial communication with the family is critical; clinicians must
be honest and sensitive to set the tone for future communication.
• Parents should not be separated from their babies, if at all possible.
• Assessment for dysmorphology can be quite subjective and requires
expertise, experience, and attention to detail.
• Documentation is important to achieve consistency among the
healthcare team.
• Some genetic conditions are characterized by common associations
that can guide the evaluation of the neonate.
• The evaluation of the neonate with a possible large or small molecule
disorder should be guided by a clinical geneticist.
What needs to be studied: • Best practices for team approaches to the care of the neonate with a
possible rare disease, particularly the use of a single spokesperson;
• Best practice approaches to communication with families of different
cultures;
• How to prepare the family for the long-term challenges they face with
a child who has a rare disease;
• The potential value of remote telemedicine consultation for the
evaluation and diagnosis of neonatal rare diseases;
• Best practices for palliative care for infants whose conditions can be
symptomatically managed only or are lethal.
What we can do today: • Keep up to date important contact information for rare disease
experts, metabolic specialists, and clinical geneticists prominently
displayed so that valuable time is not wasted looking for these
details.
• Acknowledge the critical nature of communication, both verbal and
nonverbal, used with families during the period of uncertainty while
a neonate is being evaluated for a rare disease.
• Guide neonatal caregivers to available resources for the systematic
evaluation and diagnosis of neonates with possible rare diseases/
genetic disorders.
• Emphasize a team approach to preparing the neonate with a rare
disease for discharge so that the care transition to outpatient
providers is smooth and important aspects of care are not neglected.
• Encourage caregivers to become knowledgeable about patient
advocacy resources, registries, clinical trial information, and support
groups for families of infants with rare diseases.

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 252 Smpokou et al

typically present with early and catastrophic (if not the neonate's inevitable death. Palliative care, hospice
treated immediately) neurologic symptoms and spe- care, and limitation of care are often discussed. Par-
cific biochemical findings within the first few days ents or guardians must make the most appropriate
or weeks of life. Newborns with IMDs that affect decisions for their families and infants; however, the
large molecules can present with facial dysmorphia, genetic and other specialists are responsible for pro-
major organ malformations, and biochemical distur- viding accurate, realistic, and honest information
bances in the first few days to weeks of life and typi- concerning the long-term outlook for these neonates
cally have a severe and progressive clinical course and the potential effects of any interventions.
and poor long-term neurologic outcomes.6,7 To eval-
uate for large and small molecule disorders, consul- SUMMARY
tation with an experienced clinical geneticist is para-
mount so that appropriate genetic and biochemical In caring for a neonate with a suspected genetic diag-
testing is ordered and unnecessary interventions are nosis, the neonatal clinician must have a clear under-
avoided (eg, cardiac or other surgeries in a neonate standing and appreciation of the multiple aspects of
with severe neurologic outcome and poor progno- evaluating and managing a genetic diagnosis.
sis). Specific clinical findings that are associated with Knowledge of specific genetic conditions can serve
select rare metabolic-dysmorphic syndromes are as a foundation to a well-rounded, professional, and
summarized in Table 2.8,9 comprehensive approach to the initial evaluation
and management of the dysmorphic neonate.4,7 In
circumstances involving potentially lethal diagnoses,
SPECIAL CONSIDERATIONS: the practitioner must be knowledgeable and com-
PALLIATIVE CARE AND END-OF-LIFE fortable engaging with the assistance of geneticists
DECISIONS and other specialists to provide the best possible care
to the newborn and family.
Certain genetic diagnoses suggest a different approach
to management of the neonate owing to the severe, References
progressive course of the disease and poor long-term 1. Aase JM. Diagnostic Dysmorphology. New York, NY: Plenum
prognosis. Genetic syndromes with increased risk for Medical Book Company; 1990.
2. Jones KL, Jones MC, del Campo M. Smith's Recognizable Patterns of
immediate or short-term, multi-organ, lethal compli- Human Malformation. 7th ed. Philadelphia, PA: WB Saunders; 2013.
cations include Patau syndrome (trisomy 13), 3. Gripp KW, Slavotinek AM, Gall JG, Allanson JE. Handbook of Physical
Measurements. 3rd ed. Oxford, England: Oxford University Press; 2013.
Edwards syndrome (trisomy 18), and certain large 4. Firth H, Hurst JA. Oxford Desk Reference Clinical Genetics. Oxford,
molecule IMDs.5-7 Consultation with multiple spe- England: Oxford University Press; 2005.
cialists becomes important to address each involved 5. Nussbaum RL, McInnes RR, Willard HF. Thompson & Thompson
Genetics in Medicine. 8th ed. Philadelphia, PA: WB Saunders; 2015.
organ and decide on the best course of action. At the 6. National Newborn Screening & Genetics Resource Center. http://
same time, the poor prognosis brings about a differ- genes-r-us.uthscsa.edu/resources.htm. Accessed April 2, 2015.
7. Onlilne Mendelian Inheritance in Man. http://www.omim.org/.
ent set of discussions surrounding the extent of inter- Accessed April 2, 2015.
ventions, which, in the long-term, will not improve 8. Burton BK. Inborn errors of metabolism in infancy: a guide to diagno-
sis. Pediatrics. 1998;102:e69.
life expectancy. In these cases, quality of life takes 9. Nyhan WL, Barshop BA, Ozand PT. Atlas of Metabolic Diseases. 2nd
precedence over extraordinary measures to postpone ed. Oxford University Press; 2005.

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