1. A thorough evaluation of the dysmorphic child includes obtaining a detailed family, birth, and medical history as well as a comprehensive physical exam. 2. Minor anomalies and phenotypic variants can provide clues to narrow the differential diagnosis and include features such as epicanthal folds, clinodactyly, and pigmented nevi. 3. Additional diagnostic testing may include imaging studies like x-rays if skeletal abnormalities, and laboratory testing such as karyotyping to identify chromosomal abnormalities.

1. Approach to the Dysmorphic Child

2. History
• Pedigree or family history : to assess the inheritance pattern.
• Perinatal history : pregnancy history of the mother , factors that
may relate to deformations or disruptions , maternal exposures to
teratogenic drugs or chemicals .
• Natural history of the phenotype :
1. Malformation syndromes caused by chromosomal aneuploidy or
aneusomy and single gene pleiotropic disorders are usually static.
2. Disorders that cause dysmorphic features by the mechanism of
metabolic perturbations (Hunter syndrome, Sanfilippo syndrome)
are either mild or inapparent at birth and progress relentlessly,
causing deterioration of the patient over time.

3. Physical Examination
DEFINITIONS OF COMMON CLINICAL SIGNS OF DYSMORPHIC SYNDROMES

6. MINOR ANOMALIES AND PHENOTYPE VARIANTS*
CRANIOFACIAL EYE
1. Inner epicanthal folds
1. Large fontanel
2. Telecanthus
2. Flat or low nasal bridge
3. Slanting of palpebral
3. Saddle nose, upturned fissures
nose
4. Hypertelorism
4. Mild micrognathis
5. Brushfield spots
5. Cutis aplasia of scalp

7. EAR
SKIN
1. Lack of helical fold 1. Dimpling over bones
2. Posteriorly rotated pinna
3. Preauricular with or without
2. Capillary hemangioma
auricular skin tags (face, posterior neck)
4. Small pinna 3. Mongolian spots (African
5. Auricular (preauricular) pit or Americans, Asians)
sinus
6. Folding of helix 4. Sacral dimple
7. Darwinian tubercle 5. Pigmented nevi
8. Crushed (crinkled) ear 6. Redundant skin
9. Asymmetric ear sizes
10. Low-set ears 7. Cutis marmorata

8. HAND FOOT
1. Simian creases 1. Partial syndactyly of second
2. Bridged upper palmar creases
3. Clinodactyly of fifth digit and third toes
4. Hyperextensibility of thumbs 2. Asymmetric toe length
5. Single flexion crease of fifth digit
(hypoplasia of middle 3. Clinodactyly of second toe
6. phalanx)
7. Partial cutaneous syndactyly
4. Overlapping toes
8. Polydactyly 5. Nail hypoplasia
9. Short, broad thumb
10. Narrow, hyperconvex nails 6. Wide gap between hallux and
11. Hypoplastic nails second toe
12. Camptodactyly
13. Shortened fourth digit
7. Deep plantar crease between
hallux and second toe

9. OTHERS
1. Mild calcaneovalgus
2. Hydrocele
3. Shawl scrotum
4. Hypospadias
5. Hypoplasia of labia majora

10. Imaging Studies
• If short stature or disproportionate stature (long trunk and
short limbs) is noted, a full skeletal survey should be
performed.
• The skeletal survey can yield numerous abnormal features
that can be used to narrow the differential diagnosis.
• When there are abnormal neurologic signs or symptoms,
central nervous system imaging is indicated.
• Echocardiography and renal ultrasonography, can be useful to
identify additional major or minor malformations.

11. Laboratory Studies
• Cytogenetics with Giemsa-banded peripheral leukocyte
karyotype (or chromosome) analysis has been the gold
standard and has been performed in most evaluations of the
dysmorphic child .
• Array CGH and SNP genotyping with copy number variation
(dosage detection) are the most sensitive methods for the
detection of genomic alterations associated with multiple
congenital anomalies.
• Because many chromosome abnormalities include
derangement of the termini (telomeres) of the chromosomes,
assays should detect small (submicroscopic) duplications or
deletions of the termini of the chromosomes

12. CLINICAL INDICATIONS FOR KARYOTYPE
ANALYSIS
1. At least one major and two minor malformations
2. At least two major malformations
3. Developmental OR growth retardation with two or
more major or minor anomalies

13. Diagnosis
• The clinician should organize the findings by their specificity
into potential developmental pathophysiologic processes.
• The specificity assessment is the simplest.

14. • If a child has a patent ductus arteriosus (PDA), mild growth
retardation, mild microcephaly, and holoprosencephaly (MRI
finding of failure to lateralize the forebrain), micropenis, and
ptosis, these findings can be prioritized.
• The PDA, ptosis, mild growth retardation, and mild
microcephaly are nonspecific findings (present in many
disorders or often present as isolated features not part of a
syndrome), whereas holoprosencephaly and micropenis are
present in fewer syndromes and are never normal variants

15. • With this recognition, the clinician can search for disorders
that include both holoprosencephaly and micropenis.
• The search can be performed manually using the features
index of a textbook such as Smith's Recognizable Patterns of
Human Malformation or a computerized database such as the
Winter-Baraitser Dysmorphology Database.

16. • Searching for disorders with both findings leads quickly to a
modest list of only 21 disorders.
• One of these is SLOS. The identification of this possible
diagnosis prompts the physician to return to the bedside,
realize that many of the nonspecific features in the child are
common in SLOS, and make a tentative diagnosis of this
disorder.

17. • Although holoprosencephaly is an uncommon
manifestation of SLOS, this manifestation makes sense
because of the known pathogenetic link between sonic
hedgehog and cholesterol biosynthesis.
• Because this disorder is caused by mutations in the sterol
delta-7-reductase gene and is associated with elevated 7-
dehydrocholesterol, the pediatrician can initiate a
consultation with the clinical geneticist for suspected
SLOS