Approach to a child with dysmorphism

Dr. Syeda Ismat Bukhari

Introduction The term dysmorphic is derived from the Greek words “dys”

(disordered, abnormal, painful) and “morph” (shape, form).

Dysmorphology is a discipline of clinical genetics that studies and attempts to interpret the patterns of human growth and structural defects.

Dysmorphism Vs Syndrome The child with dysmorphic signs often does not have a major

malformation, and he or she may simply have an appearance that is unusual compared with the general population and out of keeping with that of unaffected close relatives.

A syndrome is simply a recognizable pattern of dysmorphic signs that have a common cause.

Understand the difference Major malformation

with medical +/- social implications

often require surgical repair

Minor malformation

are of cosmetic significance sometimes

Normal variants

Incidence Major congenital anomalies

At birth 2 – 3 %

At 5 yrs 4 – 6 %

Minor congenital anomalies

At birth 15 %

The importance of recognizing minor anomalies Minor anomalies are often

indicators for relevant major anomalies.

Causes of malformationsCause Percent incidence

GeneticChromosomeSingle gene

15 – 25 10 – 152 – 10

Multifactorial 20 – 25

EnvironmentalMaternal diseasesUterine / PlazentalDrug / Chemicals

8 – 126 – 8 2 – 3

0.5 – 1

Twinning 0.5 – 1

Unknown 40 – 60

History of intrauterine development

Periods of malformation

Clinical approach

History Antenatal history

Problems with infertility (medications [clomid] techniques [IVF - invitro fertilization, PGD - preimplantation

genetic diagnosis, ICSI - intracytoplasmic sperm injection])  Fetal Movement (active, decreased)  Exposures (medications, tobacco, alcohol, drugs, chemicals) Illnesses (fevers, exposures to infections)  Problems (bleeding, pre-term labor, abnormal prenatal testing

or ultrasound) 

Birth history Presentation: breech/cephalic/oblique Delivery: vaginal, c-section (why?) Neonatal course (complications/problems and days hospitalized)

History Neonatal status

APGAR Anthopometric measurements Resuscitation

Newborn course Feeding Activity Obvious deformities Complications / issues

History Past Medical History

Illnesses, hospitalizations, surgeries, immunizations, medications, allergies

A detailed review of systems.

Developmental History Address parental concerns. Determine ages for milestones (gross motor, fine motor,

personal/social, language). Determine current milestones (appropriate for age?).

Family history

Take a detailed, three-generation family history

Family historyAsk for:

Birth defects Other genetic diseases Multiple miscarriages Parental ages and health status Consanguinity and geographic origin

Physical examination Growth monitoring

Measurements of the child's weight, length, and head circumference should be plotted on the standardized growth charts.

General appearance Body shape and size etc.

Physical examination

Investigations Cytogenetics is a mainstay of diagnosis in dysmorphology.

However, chromosome studies are labour intensive and relatively expensive.

To be visible, a chromosome deletion or duplication probably involves at least 3–4 kilobases of DNA10 (perhaps 15–30 genes, depending upon the location and the chromosome).

Fluorescence in situ hybridization (FISH) Prader-Willi syndrome Angelman syndrome Smith-Magenis syndrome Miller-Dieker syndrome Velo-cardio-facial syndrome DiGeorge syndrome

Whole chromosome painting (WCP) WCP is very useful for identifying the origin of additional

chromosome material that is microscopically visible but not distinctive enough to be assigned to a specific chromosome.

It can also be used to search for light microscopically invisible (cryptic) translocations where suspicion of a chromosome abnormality remains, despite a normal standard karyotype.

The exchange of similarly sized and banded material between 2 chromosomes, which is not visible in a standard study, becomes visible because of the exchange of different colours.

Other investigations Molecular (DNA) diagnostics

Biochemical lab testing (to rule out any inborn error of metabolism, storage diseases etc.)

The major problems of morphogenesis

Disruptions Morphological alterations of structures after formation

Has low recurrence risk

Causes of disruption Ionization (x-ray, radioactive substance exposure)

Hyperthermia

Infections

Teratogenic

Metabolic

Vascular disruption

Amnion rupture sequence

Deformations Due to mechanical forces that mold

a part of fetus over a prolonged time period

The musculoskeletal system may be involved, but may also be reversible post-natally

Breech presentation

Risks for fetal constraint Maternal risk factors

Primigravida Small uterus Uterine malformation Uterine fibromata Small maternal pelvis

Fetal risk factors Oligohydroamnios Large fetus Multiple gestation

Deformations related to breech presentation

Malformations

Disorders of lymphatic drainage

Cleft palate

Telecantus, hyper-/hypo-telorsim

Ear defects

Chin

Digit anomalies

Non-disjunction syndromes

Down syndrome (trisomy 21) Low set ears Hypotonia Simian crease Wide space between first and

second toe Flat face

Patau syndrome (trisomy 13) Holoprosencephaly Cutis aplasia Microcephaly Microphthalmia Cleft lip +/- palate Polydactyly Congenital heart defect

Edwards syndrome (trisomy 18)

Weak cry Polyhydroamnios Growth deficiency Low-set, malformed

auricles Clenched hand with

overlapping fingers Rocker bottom feet Congenital heart

defect

Klinefelter syndrome (47xxy)

Tall stature Behavioral issues Post-pubertal

hypogonadism

Turner syndrome (45x)Not diagnosed until 5-6

yrs Webbed neck Shield chest Cubitus vulgaris Low hairline Short stature Renal anomalies Cardiac anomalies

(bicuspid aortic valve and coarctation of aorta)

Microdeleteions

Wolf hirshorn (4p) Hypertelorism Broad nasal bridge Cleft lip +/- palate Down turned mouth Severe mental retardation

Cri-du-chat (5p) Microcephaly Growth retardation High-pitched cat-like cry Congenital heart disease Hypotonia

Contiguous gene syndrome

Prader-willi syndrome (15q11) Obesity Hypotonia Small hands and feet Upward slanting

palpebral fissures IQ : 60 – 70 Micro-penis /

cryptorchidism

Angelman syndrome (15q11) Mental retardation Puppet like gait Paroxysms of inappropriate laughter Absent / limited speech Seizures

22q11 deletion syndromes(Di-George, Velocardial-facial, Sprintzen)

Micrognathia Low set ears Short palpebral fissures Blunted nose High-arched palate Cleft palate +/- bifid uvula

Autosomal dominant syndromes

Achondroplasia (FGFR3)

Rhizomelic shortening of limbs

Short fingers held in trident configuration

Elarged head with depressed nasal bridge

Neurofibromatosis > 6 café-au-lait spots >2 neurofibromas Lisch nodules (iris hematoma) Optic gliomas Angiofibromas Axillary or inguinal freckling

Osteogenesis imperfecta Fractures Osteopenia Blue sclera Hearing loss Short stature

Four types

Autosomal recessive

Cystic fibrosis

Tay-Sacs disease

Sickle cell anemia

Teratogens

Fetal alcohol syndrome

Quiz

What are the most appropriate genetic condition associated with the following physical findings?

Webbed neck

Macrosomia

Rhizometric shortening

Small hands

Café-au-lait spots

What are the most appropriate genetic condition associated with the following physical findings?

Upward slanting palpebral fissures

Downward slanting palpebral fissures

Lich nodules

Kayser-fleischer ring

Thank you