Notes about this file

1. This file was collected from Nelson Essentials of Pediatrics, Pediatrics USMLE CK book & some
websites

2. Each 2 slides talk about 1 syndrome (description, clinical picture, Diagnosis, management,
deferential diagnosis )

3. Pictures are from google

4. Forgive me if there is any mistake … it’s a Human work

 Down Syndrome (trisomy 21)
Description:
It’s the most common chromosomal abnormality in newborns. it’s due to
the presence of extra copy of chromosome 21.

Clinical picture:
1. Upward slanting palpebral fissures 2. speckling of iris (Burchfield spot)
3. Inner epicanthal folds 4. small stature 5. mild microcephaly
6. mouth opening with tongue protrusion 7. short neck 8. flat occiput
Upward slanting palpebral fissures speckling of iris
9. Short metacarpals and phalanges 10. single palmar crease
11.hypotonia 12. hearing loss (sensorineural, conductive or mixed)
13.Primary gonadal deficiency 14. cardiac anomaly (ECD>VSD>ASD,PDA)
15. GI anomalies (duodenal atresia, Hirschprung “functional obstruction
in distal colon”) 16. Atlantoaxial instability 17. hypothyroidism
18. mental retardation 19. acute lymphocytic leukemia

Cause: related to old maternal age

Inner epicanthal folds mouth opening with tongue

Complications: protrusion
1. Early onset of Alzheimer disease 2. death from congenital heart

Diagnosis: by karyotyping
 Down Syndrome (trisomy 21)
Management:
1. Provide Accurate information
2. Breaking the news/diagnosis (Say this in a positive way)
3. Follow the patient and treat any problem as fast as possible

Differential diagnosis:
1. 49,XXXXY chromosome
2. other high-order multiple X chromosome disorders
short neck Single palmar crease
3. Congenital hypothyroidism
4. Mosaic trisomy 21 syndrome
5. Partial trisomy 21 (or 21q duplication)
6. Robertsonian trisomy 21
7. Zellweger syndrome or other peroxisomal disorders

Note:
There are 3 types of down syndrome:
1. Trisomy 21: all the cells has extra copy of chromosome 21
2. Translocation: extra part of chromosome 21 attached to another Short metacarpals and phalanges Flat occiput
chromosome in every cell
3. Mosaic: some cells has extra copy of chromosome 21 and other cells are
normal
 Edward Syndrome (trisomy 18)
Description:
It’s the 2nd most common chromosomal abnormalities in
newborns. it’s due to the presence of extra copy of chromosome
13. most of newborns die within the 1st year of life

Clinical picture:
1. Growth deficiency 2. mental retardation 3. Microcephaly
4. low set + malformed ears 5. micrognathia 6. prominent occiput low set + malformed ears micrognathia

7. clenched hand 8. Short sternum 9. VSD, ASD, PDA

10. hammer toe 11. Rocker-bottom feet 12. omphalocele

Cause: related to old maternal age

Diagnosis: by karyotyping

Management: prominent occiput clenched hand

1. No cure
2. Surgery is used to correct some abnormalities
 Edward Syndrome (trisomy 18)
Deferential diagnosis:
1. Fetal akinesia sequence
2. Trisomy 13
3. Pena-Shokeir syndrome type I
4. Genomic dosage anomalies
5. Other autosomal trisomies and monosomies
hammer toe
6. Arthrogryposis
7. CHARGE Syndrome

Note:
The newborn with trisomy 18 is weak since birth

Rocker-bottom feet
 Patau Syndrome (trisomy 13, trisomy D)
Description:
It’s the least common and most severe among all trisomies & it’s due to
the presence of extra copy of chromosome 13. it presents at birth and
Has a very poor prognosis (death with the 1st year of life)

Clinical picture:
1. Dysplastic (malformed) ears 2. Cleft lip &/or Cleft palate
3. post-axial Polydactyly 4. Microcephaly 5. VSD, ASD, PDA
Dysplastic ear Cleft lip and palate
6.Rocker-bottom feet (prominent heel bone) 7. Omphalocele
9. Microphthalmia (small eyes) 10. Scalp defects (cutis aplasia) 11. Hernias
12. Neural tube defects 13. mental retardation 14. single umbilical artery
15. Holoprosencephaly

Cause: related to old maternal age

Diagnosis:
1. Clinical presentation 2. conventional cytogenetics
Microcephaly Polydactyly
3. Fluorescent in situ hybridization (FISH)
 Patau Syndrome (trisomy 13, trisomy D)
Management:
There is no treatment to address in this condition
However, there are procedures to sustain life for a bit
(e.g.: surgery to fix defects to allow the child to survive
for as long as possible)
Microphthalmia Omphalocele
Differential diagnosis:
1. Edwards syndrome 2. Partial duplication of 13q
3. Pseudotrisomy 13 (holoprosencephaly-polydactyly syndrome)
4. Smith-Lemli-Opitz Syndrome

Note:
Mosaic Patau:
Neural tube defect cutis aplasia
is a condition where some cells will have extra genetic
material on chromosome 13 and some cells are
normal
 WAGR syndrome (aniridia-wilms tumor association)
Description:
It’s unusual complex of congenital developmental abnormalities (aniridia
“absence of the the iris”, genitourinary malformations & mental
retardation). These patients are at high risk (>30%) of having a Wilms
tumor (a tumor of the kidneys). It’s due to deletion of chromosomal
material from the short arm of chromosome 11

Clinical picture:
Aniridia cataracts
1. Aniridia 2. cataracts 3. ptosis 4. hypospadias 5. cryptorchidism
6. underdeveloped (streak) ovaries

Diagnosis:
1. Clinical presentation 2. karyotyping

Management:
1. Wilms tumor  surgery y, radiation therapy & chemotherapy
2. Aniridia  Drugs or surgery
ptosis hypospadias
3. Genitourinary problems  Surgery
4. Mental Retardation  physical, occupational and speech therapies
 WAGR syndrome (aniridia-wilms tumor association)
Differential diagnosis:
1. Denys-Drash Syndrome 2.Genital Anomalies
3. Wilms Tumor

Note:
WAGR syndrome is contiguous gene deletion
cryptorchidism
syndrome
 Klinefelter syndrome (XXY)
Description:
It’s the most common chromosomal disorder associated with male
hypogonadism and infertility. It’s due to additional X or Y chromosome

Clinical picture:
1. Mental retardation 2. psychosocial problems 3. long limb 4. slim
4. Hypogonadism 5. gynecomastia 6. hypogenitalism
7. elevated urinary gonadotropin 8. erectile dysfunction 9. osteoporosis
gynecomastia hypogenitalism
10. subnormal libido 11. poor self-esteem
12. hyalinization and fibrosis of the seminiferous tubules

Diagnosis:
1. Clinical presentation 2. Karyotyping 3. hormone testing

Management :
1. Testosterone replacement 2. speech and language therapy
3. Physical and occupational therapy 4. intracytoplasmic sperm injection
long limb

Differential diagnosis:
1. Fragile X Syndrome 2. Genetics of Marfan Syndrome 3. Hypogonadism
 Klinefelter syndrome (XXY)
Note:
There are many variants of Klinfelter syndrome
depending on the egg and sperm combination and
some of these are:

1. XXY  the most common

2. XYY  incomputable with life
3. XXXY, XXXXXY
 Turner Syndrome (XO)
Description:
It’s one of the most common chromosomal abnormalities in female
infants. it’s caused by the absence of one set of genes from the short
arm of one X chromosome.

Clinical picture:
1. Short stature 2. gonadal dysgenesis (streak ovaries)
3. congenital lymphedema (lead to dorsum puffiness) 4. Broad chest
streak ovaries Short stature
5. wide-spaced nipples 6. webbed neck 7. Low posterior hair line
8. Cubitus valgus 9. horseshoe kidneys 10. Bicuspid aortic valve
11. coarctation 12. aortic stenosis 13. HTN 14. mitral prolapse

Cause: Not related to old maternal age

Diagnosis:
1. Prenatal:
A. nuchal cystic hygroma B. horseshoe kidney
congenital lymphedema wide-spaced nipples
with puffiness
2. Karyotyping (confirmatory test):
the presence of a 45,X cell line or a cell line with deletion of the short
arm of the X chromosome (Xp deletion)
 Turner Syndrome (XO)
Management:
1. Growth hormone therapy
2. Estrogen replacement therapy
3. Cardiac surgery (when needed)
4. In vitro fertilization (to achieve pregnancy)
5. Psychological help
webbed neck Low posterior hair line

Differential diagnosis:
Noonan Syndrome

Cubitus valgus
 Fragile X Syndrome (Martin-Bell syndrome, marker X syndrome)

Description:
It’s a X-linked dominant syndrome that is found to be the most common
cause of inherited mental retardation. It’s due to fragile site on the long
arm of chromosome X in some males and some carrier females

Clinical picture:
1. Mild to prefund mental retardation 2. learning problems 3. large ears
4. Large jaw 5. long face 6. macroorchidism (large testes)
large ears Large jaw

Diagnosis:
1. Radiography of the spine  evaluate for scoliosis.
2. Echocardiography  exclude mitral valve prolapse
3. Cytogenetics

Management :
• treating the medical problems that these patients commonly
experience including:
macroorchidism Long face
1. gastroesophageal reflux 2. sinusitis 3. otitis media
• During infancy:
healthcare maintenance visits & focus examination on:
1. possible hip dislocations 2. hernias 3. hypotonia
 Fragile X Syndrome (Martin-Bell syndrome, marker X syndrome)

Differential diagnosis:
1. Asperger Syndrome 2. Autism 3. Rett Syndrome
4. Genetics of Marfan Syndrome
5. Gigantism and Acromegaly 6. Prader-Willi Syndrome
7. Pediatric Attention Deficit Hyperactivity Disorder
(ADHD) 8. Pervasive Developmental Disorder
 Beckwith-Wiedemann syndrome
Description:
It’s the most common overgrowth syndrome in infancy. It’s due to a
problem in the short arm of chromosome 11 that results in over
activation of IGF-2.

Clinical picture:
1. Macrosomia (large birth weight) 2. Macroglossia 3. hemihypertrophy
4. Hypoglycemia (due to β cell hyperplasia)
Macrosomia Macroglossia
6. Umbilical abnormalities (e.g.: diastasis recti, omphalocele)

Diagnosis:
1. Simple glucose test
2. At the time of hypoglycemia obtain plasma ketones, plasma free
fatty acid, serum insulin & serum IGF levels
3. Random urine collection  Screen for hypercalciuria

Management :
hemihypertrophy diastasis recti
Obtain ultrasounds and serum Alfa fetoprotein every 6 months in first 6
years of life to look for Wilms tumor and hepatoblastoma
 Beckwith-Wiedemann syndrome
Differential diagnosis:
1. Congenital Hyperinsulinism 2. Hyperinsulinism
3. Fluid, Electrolyte, and Nutrition Management of the Newborn 4. Hyperpituitarism 5. Obesity
6. Genetics of Glycogen-Storage Disease Type I 7. Glycogen-Storage Disease Type 0
8. Pediatric Hypoglycemia 9. Splenomegaly 10. Pediatric Omphalocele and Gastroschisis
 Prader-Willi Syndrome
Description:
It’s a rare genetic disorder that is due to a deletion or disruption of
genes in the proximal arm of paternal chromosome 15 or by maternal
disomy in the proximal arm of chromosome 15

Clinical picture:
1. Difficulty in feeding + poor growth followed by increased feeding and
weight gain (in 1st year life) 2. short stature 3. obesity (6 months – 6 years)
4. Mild to severe mental retardation 5. food behavioral problems Small and puffy feet Small and puffy hands
6. Small and puffy hands & feet 7. small genitalia 8. hypogonadism
9. hypothalamic-pituitary dysfunction

Diagnosis:
A. chromosomal or microarray analysis
B. assessment for methylation patterns in the chromosomal region (by
Southern blot hybridization or polymerase chain reaction “PCR”)
C. Samples from both parents and the child for underlying uniparental
disomy analysis small genitalia
D. Fluorescent in situ hybridization (FISH) used to confirm prenatal
diagnosis
E. Test both biological parents for the presence of asymptomatic
mutations in the imprinting center (In a patient with an imprinting center mutation)
 Prader-Willi Syndrome
Management :
1. Initial management of hypotonia or poor feeding
2. Evaluation for hypogonadism or hypopituitarism
3. Management of obesity
4. Monitoring for scoliosis
5. Therapy for behavioral issues

Differential diagnosis:
1. anxiety Disorder: Obsessive-Compulsive Disorder 2. Childhood Sleep Apnea
3. Fragile X Syndrome 4. Hypogonadism 5. Nutritional Considerations in Failure to Thrive
6. Obesity 7. Osteoporosis 8. Pediatric Cryptorchidism Surgery
9. Pediatric Growth Hormone Deficiency 10. Pediatric Obesity-Hypoventilation Syndrome
10. Short Stature
 Angelman Syndrome (happy puppet syndrome)
Description:
It’s a neurodevelopmental disorder that occurs due to deletion or
inactivation of genes on the maternally inherited chromosome 15

Clinical picture:
1. Sever mental retardation 2. paroxysms on inappropriate laughter
3. Absent speech (< 6 words) 4. ataxia 5. jerky arm movement
6. Seizures (start at age 4 & stop at age 10)

Diagnosis:
A. A history of delayed motor milestones and then later a delay in
general development (especially of speech)
B. Unusual movements including fine tremors, jerky limb movements,
hand flapping and a wide-based, stiff-legged gait
C. Characteristic facial appearance
D. A history of epilepsy and an abnormal EEG tracing
E. A happy disposition with frequent laughter
F. array comparative genomic hybridization shows A deletion or
inactivity on chromosome 15
 Angelman Syndrome (happy puppet syndrome)
Management :
1. Anti-seizure medication  to control seizures
2. Physical therapy  help with walking and movement problems
3. Communication therapy
4. Behavior therapy

Differential diagnosis:
1. Prader-Willi Syndrome 2. X-linked Mental Retardation Syndrome 3. Rett Syndrome
4. Phelan-McDermid Syndrome 5. Mowat-Wilson Syndrome 6. Monosomy 1p36 Syndrome
7. Smith-Magenis Syndrome 8. Chromosome 17q21.31 Microdeletion 9. Pitt-Hopkins
10. Chromosome 2q23.1 Microdeletion Syndrome
 Pierre Robin syndrome (Robin sequence)
Description:
It’s congenital condition of facial abnormalities in humans. It’s
Autosomal recessive variant & X-linked variant

Clinical picture:
1. Micrognathia 2. Retroglossia 3. cleft soft palate

Diagnosis:
Based on clinical picture Micrognathia Cleft soft palate

Management:
1. keep the upper airway open 2. repair cleft palate (after 12 months old)
3. tympanostomy tubes to improve hearing

Differential diagnosis:
1. Beckwith-Wiedemann Syndrome 2. CHARGE Syndrome
3. Childhood Sleep Apnea 4. DiGeorge Syndrome
5. Fetal Alcohol Syndrome 6. Multiple Births 7. Pectus Excavatum
8. Mandibulofacial Dysostosis (Treacher Collins Syndrome)
9. Pediatric Cleft Lip and Palate 10. Velocardiofacial Syndrome
 Achondroplasia/Hypochondroplasia
Description:
It’s an autosomal dominant new gene mutation in the fibroblast growth
factor receptor 3 that is related to older paternal age

Clinical picture:
1. Short stature (increased upper : lower ratio) 2. short-limb dwarfism
3. Proximal femur shorting 4. megalencephaly 5. small foramen magnum
6. Hydrocephaly 7. small cranial base 8. prominent forehead
9. lumbar lordosis short-limb dwarfism Proximal femur shorting

Diagnosis:
• Cytogenetics:
1. Plasma can be analyzed for the FGFR3 mutation in the mother when
a short-limb skeletal dysplasia is diagnosed prenatally on ultrasound
2. DNA testing can be performed when both of the parents are
affected.

Management: prominent forehead lumbar lordosis

somatotropin (recombinant human growth hormone)

Differential diagnosis:
1. Diastrophic Dysplasia 2.Spondyloepiphyseal Dysplasia
 Marfan syndrome
Description:
It’s an autosomal dominant genetic disorder of connective tissue that
happens due to mutation in fibrillin-1 gene.

Clinical picture:
1. Tall stature 2. long and slim limbs 3. arachnodactyly 4. joint laxity
5. decreased upper : lower ratio 6. kyphoscoliosis 7. pectus excavatum
8. pectus carinatum 9. lens subluxation (defect in suspensory ligament)
kyphoscoliosis lens subluxation
10. Secondary glaucoma 11. myopia 12. retinal detachment
13. ascending aorta dilatation ∓ aneurysm 14. aortic regurgitation
15. mitral prolapse

Diagnosis:
1. Clinical picture 2. molecular studies for fibrillin-1 gene

Management :
1. Moderate restriction of physical activity 2. Endocarditis prophylaxis
glaucoma retinal detachment
3. Echocardiography at annual intervals 4. Beta-blocking treatment
 Marfan syndrome
Differential diagnosis:
1. Fragile X Syndrome 2. Genetics of Ehlers-Danlos Syndrome 3. Gigantism and Acromegaly
4. Hyperpituitarism 5. Hyperthyroidism 6. Klinefelter Syndrome 7. Loeys-Dietz Syndrome
 Ehlers-Danlos syndrome
Description:
It’s group of more than 10 different inherited disorders all involve a
genetic defect in collagen and connective-tissue synthesis and structure.
It’s an autosomal dominant with wide verity

Clinical picture:
1. Droopy ears 2. Hyperextensible skin 3. fragile skin 4. easy bruisability
5. poor wound healing 6. Joint hyperlaxity (tendency toward hip, shoulder, knee &
Droopy ears Hyperextensible skin
clavicular dislocation) 7. mitral prolapse 8. tricuspid prolapse 9. ASD
10. aortic root dilatation 11. dissecting aneurysm 12. Blue sclera
13. Myopia 14. glaucoma 15. ectopia lentis 16. retinal detachment
17. Intracranial aneurysm

Diagnosis:
1. Clinical presentation 2. collagen gene mutation testing
3. collagen typing via skin biopsy 4. echocardiogram
5. lysyl hydroxylase or oxidase activity
fragile skin easy bruisability

Management :
1. Close monitoring of the cardiovascular system 2. physiotherapy
3. occupational therapy 4. orthopedic instruments
 Ehlers-Danlos syndrome
Differential diagnosis:
1. Cutis Laxa (Elastolysis) 2. Loeys-Dietz syndrome
3. Pseudoxanthoma Elasticum

Note:
There are 6 major types of Ehlers-Danlos syndrome
Joint hyperlaxity Blue sclera
that have different genetics, presentation, prognosis &
managment

ectopia lentis retinal detachment

 Fetal alcohol syndrome
Description:
It’s an adverse fetal, neonatal, and pediatric effects occur with maternal
alcohol consumption during pregnancy

Clinical picture:
1. Prenatal growth deficiency (e.g.: intrauterine growth restriction)
2. postnatal growth deficiency (short stature) 3. Mental retardation
4. Microcephaly 5. Fine motor dysfunction 6. Irritability in infancy
abnormal frontal lobe development maxillary hypoplasia
7. hyperactivity in childhood 8. Behavioral abnormalities
9. Mid-face dysmorphism (abnormal frontal lobe development)
10. short palpebral fissures 11. maxillary hypoplasia 12. short nose
13. smooth philtrum 14. thin and smooth upper lip
15. Joint abnormalities (e.g.: abnormal position and/or function)
16. Cardiac anomalies: VSD > ASD, tetralogy of Fallot

Diagnosis:
1. Confirmed alcohol consumption by the mother
short nose smooth philtrum
2. characteristic facial anomalies
3. growth retardation
4. CNS involvement
 Fetal alcohol syndrome
Management:
Treat the associated birth defects

Differential diagnosis:
1. Phenocopies 2. Fetal toluene embryopathy
3. Dubowitz syndrome 4. Maternal phenylketonuria
thin and smooth upper lip
5. Some cases of 22q11 deletion
Fetal hydantoin syndrome (fetal dilantin syndrome)

Description:
It’s a group of defects caused to the developing fetus by exposure to the
teratogenic effects of phenytoin or carbamazepine

Clinical picture:
1. Growth deficiency 2. Borderline to mild mental retardation
3. Dysmorphic facial features 4. short neck 5. abnormal palmar crease
6. Rib abnormalities 7. Hirsutism 8. Cupid’s-bow lips (arrow like)
abnormal palmar crease Hirsutism

Diagnosis:
1. No diagnostic testing that can identify fetal hydantoin syndrome
2. A diagnosis is made clinically based upon identification of
characteristic symptoms in an affected infant in conjunction with a
history of phenytoin exposure during gestation

Management:
Treat the associated symptoms
Cupid’s-bow lips

Differential diagnosis:
1. Coffin-Siris syndrome 2. Fetal alcohol syndrome
3. Fetal valproate syndrome
 Fetal valproate syndrome
Description:
It happens whne a baby develops signs and symptoms as a result of an
exposure to valproic acid during fetal development.

Clinical picture:
1. Midface hypoplasia (e.g.: cleft lip) 2. Cardiac defects 3. convex nails
4. Meningomyelocele 5. Long, thin fingers and toes

convex nails Meningomyelocele

Diagnosis:
1. pregnancy history that includes exposure to valproic acid
2. diagnosis of exclusion

Management:
No specific treatments& each symptom or birth defect is managed
individually

Differential diagnosis:
Long, thin fingers and toes
Teratogenic effect from any anticonvulsant taken during pregnancy
 Retinoic acid embryopathy
Description:
a characteristic pattern of mental and physical birth defects that results
from maternal use of retinoids, the synthetic derivatives of vitamin A,
during pregnancy

Clinical picture:
1. Mild facial asymmetry 2. bilateral microtia/anotia
3. facial nerve paralysis ipsilateral to ear 4. narrow, sloping forehead
anotia microtia
5. abnormal mottling of teeth 6. Conotruncal malformations
7. CNS malformations 8. Decreased intelligence
9. Thymic and parathyroid abnormalities

Diagnosis:
1. pregnancy history that includes exposure to valproic acid
2. diagnosis of exclusion

Management:
facial nerve paralysis ipsilateral to ear
Isotretinoin

Differential diagnosis:
Teratogenic effect from any anticonvulsant taken during pregnancy
 Potter's syndrome
Description:
ypical physical appearance of a fetus or neonate due to oligohydramnios
experienced in the uterus

Clinical Picture:
1. fetal compression (mid-face, ears) 2. pulmonary hypoplasia
3. Potter facies (e.g.: hypertelorism, epicanthal folds, low-set flattened ears, micrognathia,
compressed flat nose) 4. Breech presentation (pelvic-first delivery)
5. Abnormal positioning of hands and feet 6. limb anomalies

Diagnosis:
1. Serum electrolyte tests 2. Serum creatinine levels 3. CBC with
differential 4. Urinalysis 5. cultures of the urine, blood & CSF
6. Chromosomal analysis
Potter face

Management:
1. Treat the renal failure 2. mechanical ventilation 3. surgery

Differential diagnosis:
1. Bilateral renal agenesis 2. Multicystic Renal Dysplasia 3. Polycystic
Kidney Disease 4. Posterior Urethral Valves 5. Prune belly syndrome
 Horner syndrome
Description:
It’s due to an interruption of the sympathetic nerve supply to the eye and it’s characterized by the classic triad of:
1. miosis 2. partial ptosis 3. loss of hemifacial sweating

Clinical picture:
1. First-order neuron lesions:
Hemisensory loss, dysarthria, dysphagia, ataxia, vertigo, and nystagmus

2. Second-order neuron lesions:

Prior trauma facial, neck, axillary, shoulder or arm pain, cough, hemoptysis, previous thoracic or neck surgery, previous chest
tube or central venous catheter placement or neck swelling

3. Third-order neuron lesions:

Diplopia from sixth nerve palsy, numbness in the distribution of the first or second division of the trigeminal nerve and pain

Causes:
1. Lesion of the primary neuron 2. Brainstem stroke or tumor
3. Trauma to the brachial plexus 4. Tumors (eg, Pancoast)
5. infection of the lung apex 6. Lesion of the postganglionic neuron
7. Dissecting carotid aneurysm 8. Carotid artery ischemia 9. Migraine
10. Middle cranial fossa neoplasm
 Horner syndrome
Diagnosis:
1. CBC 2. Fluorescent treponemal antibody absorption
3. Venereal Disease Research Laboratory
4. Purified protein derivative placement 5. Urine test

Management:
1. depends on the underlying cause
2. The goal of treatment is to eradicate the
underlying disease process

Differential diagnosis:
1. Adie pupil 2. Anisocoria 3. Argyll Robertson pupil
4. Holmes-Adie pupil (contralateral)
5. Iris sphincter muscle damage 6. Senile miosis
7. Third nerve palsy 8. Unilateral use of miotic drugs
9. Unilateral use of mydriatic drugs
 Sturge–Weber syndrome
Description:
it’s a rare congenital neurological and skin disorder & it’s one of the
phakomatoses

Clinical picture:
1. port-wine stains of the face 2. glaucoma 3. seizures
4. mental retardation 5. ipsilateral leptomeningeal angioma

port-wine stains of the face glaucoma

Diagnosis:
1. Skull radiography 2. Angiography 3. Computed tomography (CT)
4. Magnetic resonance imaging (MRI) 5. MRI with gadolinium
6. Functional imaging With:
A. single-photon emission computed tomography (SPECT)
B. positron emission tomography (PET)

Management:
1. Anticonvulsants 2. Glaucoma medications
ipsilateral leptomeningeal angioma
3. Dye laser photocoagulation
4. Surgery:
only in patients who have refractory seizures, glaucoma or specific
problems related to various SWS-associated disorders such as scoliosis
 Sturge–Weber syndrome
Differential diagnosis:
1. Complex Partial Seizures 2. Epilepsia Partialis Continua
3. Epilepsy and Seizures 4. Generalized Tonic-Clonic Seizures
5. Hemangioma, Capillary 6. Migraine Headache
6. Partial Epilepsies 7. Pediatric First Seizure
8. Pediatric Status Epilepticus 9. Vagus Nerve Stimulation
 Hunter syndrome
Description:
it’s a lysosomal storage disease caused by a deficient (or absent)
enzyme, iduronate-2-sulfatase (I2S). The accumulated substrates in
Hunter syndrome are heparan sulfate and dermatan sulfate. The
syndrome has X-linked recessive inheritance.

Clinical picture:
1. coarse facies 2. short stature 3. skeletal deformities 4. joint stiffness
coarse facies
5. developmental delay 6. intellectual disability

Diagnosis:
1. Urine spot tests
2. electrophoretic techniques:
differentiates Heparan sulfate, keratan sulfate (KS) & dermatan sulfate
3. Gene Tests: enzymatic and mutation analysis

Management:
1. treat the symptoms 2. bone marrow transplant
3. enzymatic replacement
 Hunter syndrome
Differential diagnosis:
1. Genetics of Mucopolysaccharidosis Type III or VII 2.Mucopolysaccharidosis Type I H/S
3. Mucopolysaccharidosis Type IH or IS 4. Multiple Sulfatase Deficiency
 DiGeorge syndrome
Description:
it’s one of a group of phenotypically similar disorders including:
1. velocardiofacial syndrome (VCFS, or Shprintzen syndrome)
2. conotruncal anomaly face (CTAF) syndrome
all share a common microdeletion known as the DGS critical region on
chromosome 22 at band q11.2

Clinical picture:
micrognathia Narrow palpebral fissures
1. Retrognathia or micrognathia 2. Long face 3. Narrow palpebral fissures
4. High and broad nasal bridge 5. Small teeth 6. Downturned mouth
7. Asymmetrical crying face 8. Short philtrum 9. Low-set, malformed ears
10. Hypertelorism

Management:
1. treat the symptoms

High and broad nasal bridge Downturned mouth

 DiGeorge syndrome
Diagnosis:
1. Genetic studies:
A. Chromosomal microarray analysis (CMA)
B. array comparative genomic hybridization (aCGH)
C. Fluorescent in situ hybridization (FISH)
D. TBX1 gene studies
E. Multiplex ligation-dependent probe amplification (MLPA)

Asymmetrical crying face Short philtrum

2. Additional laboratory tests:
A. CBC B. Serum calcium and parathyroid hormone (PTH) studies

3. Evaluation of T-cell count and function

A. flow cytometry B. Reverse-transcriptase polymerase chain reaction
C. Antibody response studies

Differential diagnosis:
1. Velocardiofacial syndrome
Hypertelorism
2. Conotruncal anomaly face (CTAF) syndrome
3. Cayler syndrome
Description:
Noonan syndrome
It’s a relatively common autosomal dominant congenital disorder that
affects both males and females. It’s referred to as the male version of
Turner's syndrome. however, the genetic causes of Noonan syndrome
and Turner syndrome are distinct

Clinical picture:
1. congenital heart defect (pulmonary valve stenosis, ASD & hypertrophic cardiomyopathy)
2. short stature 3. learning problems 4. pectus excavatum
5. impaired blood clotting 6. webbed neck 7. flat nose bridge

Diagnosis:
1. Cardiac evaluation: Including echo ECG
2. Ophthalmologic and audiologic evaluation
3. Coagulation screen
4. Renal ultrasonographic examination
5. Developmental assessment

Management:
1. Growth hormone 2. Careful follow-up evaluation
Noonan patient

Differential diagnosis: Fetal Alcohol Syndrome

 Metabolic Syndrome
Description:
a multiplex risk factor that arises from insulin resistance accompanying
abnormal adipose deposition and function

Clinical picture:
1. Central abdominal obesity 2. Chest pains or SOB
3. Acanthosis nigricans (brown hyperpigmentation found in body folds)
4. hirsutism 5. peripheral neuropathy 6. retinopathy
Acanthosis nigrican Central obesity
7. Xanthomas (cholesterol depositions anywhere in the body)
8. Xanthelasmas (small sharply demarcated fat deposition under the skin)

Complications:
1. coronary heart disease 2. DM 3. fatty liver 4. cancer

Diagnosis:
1. Clinically: Central obesity + hyperglycemia
2. Lab tests:
Xanthelasmas Hirsutism
A. Fasting glucose ≥100 mg/dL B. Blood pressure ≥130/85 mm Hg
C. Triglycerides ≥150 mg/dL D. HDL-C < 40 mg/dL in men or < 50 mg/dL
in women
E. Waist circumference ≥102 cm in men or ≥88 cm in women
 Metabolic Syndrome
Management:
1. Elevated LDL-C levels  Statins
2. Decreased HDL-C levels  niacin
3. Elevated triglyceride levels  niacin, fibrates & omega-3 fatty acids
4. Hyperglycemia  Insulin-sensitizing agent (e.g.: metformin)

Deferential diagnoses:
• HTN:
1. obstructive sleep apnea or other sleep-related breathing disorders
2. renovascular disease
3. disorders of renin and aldosterone metabolism

• dyslipidemia: hereditary disease

• Hyperglycemia:
1. diabetes mellitus 2. thyroid dysfunction 3. glucagonomas 4. pheochromocytomas
 Sudden infant death Syndrome
Description:
the sudden death of an infant younger than 1 year that remains
unexplained after a thorough case investigation including:
1. performance of a complete autopsy 2. examination of the death scene
3. review of the clinical history

Clinical picture:
infant who is put to bed after feeding (breast or bottle) and the baby is
found dead in the position in which he or she had been placed at
bedtime. Most of infants are apparently healthy many parents state that
their babies “were not themselves” in the hours before death
And they had Diarrhea, vomiting, and listlessness in the 2 weeks before
death

Causes:
1. Cyanosis 2. Breathing difficulties 3. Abnormal limb movements
4. Child abuse

Diagnosis:
Clinical (based on history)
 Sudden infant death Syndrome
Differential diagnosis:
1. Abdominal Trauma, Blunt 2. Acute Anemia 3. Alcohol Toxicity

4. Anomalous Left Coronary Artery From the Pulmonary Artery

5. Aspiration Syndromes 6. Bronchiolitis 7. CBRNE - Botulism

8. Carbon Monoxide Toxicity 9. Cardiomyopathy, Hypertrophic

10. Child Abuse 11. Child Abuse and Neglect 12. Chronic Anemia

13. Coarctation of the Aorta 14. Coronary Artery Anomalies

 Other syndromes
• Vulnerable child syndrome:
Description:
It’s a condition in which the children perceived to be at risk for behavioral, developmental, or medical problems.

Management:
1. Address the connection between past and present episodes
2. Re-educate parents about their child's health
3. Note normal findings 4. Regular communication 5. Be exact and clear
6. Support parents in changes

• Small left colon syndrome:

transient delay in development of left side of colon presents with abdominal distention

• Caudal regression syndrome:

spectrum of structural neurologic defects of the caudal region of spinal cord which may result in neurologic impairment (hypo,
aplasia of pelvis & LE)

• Gilbert syndrome:
elevated levels of unconjugated bilirubin in the bloodstream (hyperbilirubinemia), but this normally has no serious
consequences, although mild jaundice may appear under conditions of exertion or stress
 Other syndromes
• Bronze baby syndrome:
occurs with direct hyperbilirubinemia dark, grayish-brown discoloration of the skin

• Crigler-Najjar syndrome:
It’s a rare inherited disorder affecting the metabolism of bilirubin, a chemical formed from the breakdown of the heme in red
blood cells. The disorder results in a form of nonhemolytic jaundice, which results in high levels of unconjugated bilirubin and
often leads to brain damage in infants. The disorder is inherited in an autosomal recessive manner

• Dubin–Johnson syndrome:
it’s an autosomal recessive disorder that causes an increase of conjugated bilirubin in the serum without elevation of liver
enzymes (ALT, AST). This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the
bile, and is similar to Rotor syndrome. It is usually asymptomatic, but may be diagnosed in early infancy based on laboratory
tests.

• Rotor syndrome:
it’s a rare, relatively benign autosomal recessive[2] bilirubin disorder. It is a distinct, yet similar disorder to Dubin–Johnson
syndrome

• Lowe Syndrome:
It’s a rare X-linked recessive disorder characterized by congenital cataracts, hypotonia and areflexia, intellectual disability,
proximal tubular acidosis, aminoaciduria, phosphaturia, and low-molecular-weight proteinuria.
 Other syndromes
• Soto’s syndrome:
Description:
is a rare genetic disorder characterized by excessive physical growth during the first years of life

Clinical picture:
1. overgrowth 2. advanced bone age 3. macrodolichocephaly 4. downslanting palpebral fissures 5. pointed chin
6. intellectual impairment 7. behavioral problems 8. scoliosis 9. Seizures 10. heart or kidney defects 11. hearing loss
12. problems with vision

• Perlman syndrome:
It’s a rare overgrowth disorder present at birth. It is characterized by polyhydramnios and fetal overgrowth, including
macrocephaly, neonatal macrosomia, visceromegaly, dysmorphic facial features, and an increased risk for Wilms' tumor at an
early age. The prognosis for Perlman syndrome is poor and it is associated with a high neonatal mortality

• Seckel syndrome:
It’s an extremely rare congenital nanosomic disorder. Inheritance is autosomal recessive. characterized by intrauterine growth
retardation and postnatal dwarfism with a small head, narrow bird-like face with a beak-like nose, large eyes with down-slanting
palpebral fissures,receding mandible and intellectual disability
 Other syndromes
• Rubinstein-Taybi syndrome:
It’s a condition characterized by short stature, moderate to severe learning difficulties, distinctive facial features, and broad
thumbs and first toes

• cerebro-oculo-facio-skeletal syndrome:
It’s an autosomal recessive inherited disorder characterized by congenital microcephaly, congenital cataracts and/or
microphthalmia, arthrogryposis, severe developmental delay, severe postnatal growth failure and facial dysmorphism with
prominent nasal root and/or overhanging upper lip

• Falling out syndrome:

It’s a culture-bound syndrome that is described as constricted consciousness as a psychological response to anxiety and specific
stressors. Sudden collapse characterizes episodes of falling-out, whether without warning or preceded by dizziness and a
spinning sensation. The individual suffering from symptoms of falling out can usually hear and understand what is going on
around them. It’s not treated as an illness unless it becomes disabling. It is often seen as a normal response to stressful
situations, funerals, or when a person receives shocking information

• Munchausen by proxy syndrome:

It’s a psychiatric factitious disorder where in those affected feign disease, illness, or psychological trauma to draw attention,
sympathy, or reassurance to themselves. It fits within the subclass of factitious disorder with predominantly physical signs and
symptoms, but they also have a history of recurrent hospitalization, travelling, and dramatic, extremely improbable tales
of their past experiences
 Other syndromes
• Refeeding syndrome:
It’s a metabolic disturbances that occur as a result of reinstitution of nutrition to patients who are starved or severely
malnourished.

• psychosocial short stature syndrome:

It’s a growth disorder that is observed between the ages of 2 and 15, caused by extreme emotional deprivation or stress. The
symptoms include decreased growth hormone (GH) and somatomedin secretion, very short stature, weight that is inappropriate
for the height, and immature skeletal age.

• Neonatal withdrawal syndrome:

It’s a withdrawal syndrome of infants, caused by the cessation of the administration of licit or illicit drugs. Tolerance, dependence
and withdrawal may occur as a result of repeated administration of drugs or even after short-term high dose use. There are two
types of NAS: prenatal and postnatal. Prenatal NAS is caused by discontinuation of drugs taken by the pregnant mother, while
postnatal NAS is caused by discontinuation of drugs directly to the infant

• Fröhlich syndrome:
It’s a constellation of endocrine abnormalities believed to result from damage to the hypothalamus, a part of the brain where
certain functions such as sleep cycles and body temperature are regulated
 Other syndromes
• Mauriac syndrome:
It’s a rare complication in children and adolescents with diabetes mellitus type 1, characterized by hepatomegaly, growth
impairment, and cushingoid features. It can occur as a result of abnormal blood sugar levels and the symptoms tend to rectify
with attainment of euglycemia (normal blood sugar levels)

• Laurence–Moon syndrome:
It’s a rare autosomal recessive genetic disorder associated with retinitis pigmentosa, extra digits, spastic paraplegia,
hypogonadism and mental retardation

• Gitelman syndrome:
It’s an autosomal recessive kidney disorder characterized by hypokalemic metabolic alkalosis with hypocalciuria and
hypomagnesemia. It is caused by loss of function mutations of the thiazide sensitive sodium-chloride symporter (also known as
NCC, NCCT, or TSC) located in the distal convoluted tubule

• Gordon syndrome (Pseudohypoaldosteronism type II):

it’s a condition that mimics hypoaldosteronism. However, the condition is due to a failure of response to aldosterone, and levels
of aldosterone are actually elevated, due to a lack of feedback inhibition.
 Other syndromes
• Fanconi syndrome:
It’s a disease of the proximal renal tubules of the kidney in which glucose, amino acids, uric acid, phosphate and bicarbonate are
passed into the urine, instead of being reabsorbed. It may be inherited, or caused by drugs or heavy metals

• Systemic inflammatory response syndrome:

it’s a serious condition related to systemic inflammation, organ dysfunction, and organ failure. It is a subset of cytokine storm, in
which there is abnormal regulation of various cytokines.it’s also closely related to sepsis in which patients satisfy criteria for SIRS
and have a suspected or proven infection

• Ectopia Lentis syndrome:

it’s a displacement or malposition of the eye's crystalline lens from its normal location. A partial dislocation of a lens is termed
lens subluxation or subluxated lens (a complete dislocation of a lens is termed lens luxation or luxated lens)

• Shprintzen-Goldberg syndrome:
It’s a multiple anomaly syndrome that has craniosynostosis, multiple abdominal hernias, cognitive impairment, and other skeletal
malformations as key features. Several reports have linked the syndrome to a mutation in the FBN1 gene

• Usher syndrome:
It’s a relatively rare genetic disorder caused by a mutation in any one of at least 11 genes resulting in a combination of hearing
loss and visual impairment, and is a leading cause of deafblindness.
 Other syndromes
• hereditary cancer syndrome:
It’s a genetic disorder in which inherited genetic mutations in one or more genes predispose the affected individuals to the
development of cancers and may also cause the early onset of these cancers. Cancer syndromes often show not only a high
lifetime risk of developing cancer, but also the development of multiple independent primary tumors

• Cat Eye Syndrome (Schmid–Fraccaro syndrome):

It’s a rare condition caused by the short arm (p) and a small section of the long arm (q) of human Chromosome 22 being present
three (trisomic) or four times (tetrasomic) instead of the usual two times. The term "Cat Eye" syndrome was coined because of
the particular appearance of the vertical colobomas in the eyes of some patients. However, over half of the CES patients in the
literature do not present with this trait.

• Stickler syndrome:
It’s a group of genetic disorders affecting connective tissue, specifically collagen. Stickler syndrome is a subtype of
collagenopathy, types II and XI. Stickler syndrome is characterized by distinctive facial abnormalities, ocular problems, hearing
loss, and joint problems

• Kabuki syndrome:
It’s a pediatric congenital disorder of suspected genetic origin with multiple congenital anomalies and intellectual disabilities
 Other syndromes
• Reye syndrome:
it’s an extremely rare rapidly progressive encephalopathy which usually begins shortly after recovery from an acute viral illness,
especially influenza and varicella (chickenpox). It is a potentially fatal syndrome that has numerous detrimental effects on many
organs, especially the brain and liver, as well as causing hyperammonemia (elevated blood ammonia level) and low blood sugar.
The classic features are a rash, vomiting, and liver damage. The exact cause is unknown and while it has been associated with
aspirin consumption by children with viral illness it also occurs in the absence of aspirin use. The disease causes fatty liver with
minimal inflammation and cerebral edema (swelling of the brain). The liver may become slightly enlarged and firm, and there is a
change in the appearance of the kidneys. Jaundice is not usually present

• Occipital horn Syndrome:

considered a variant of Ehlers-Danlos syndrome & it’s X-linked recessive connective tissue disorder. It is caused by a deficiency in
the transport of the essential mineral copper, associated with mutations in the ATP7A gene. It’s considered a milder variant of
Menkes disease

• Cri du chat (Lejeune syndrome):

It’s a rare genetic disorder due to a missing part (deletion) of chromosome 5. Its name is a French term (cat-cry or call of the cat)
referring to the characteristic cat-like cry of affected children.

• donohue syndrome:
it’s an extremely rare and severe genetic disorder with elfin features and are smaller than usual. Affected individuals have
an insulin receptor with greatly impaired functionality
 Other syndromes
• Alagille syndrome:
Description:
It’s a genetic disorder that affects the liver, heart, kidney, and other systems of the body. Problems associated with the disorder
generally become evident in infancy or early childhood. The disorder is inherited in an autosomal dominant pattern

Clinical presentation:
1. Jaundice 2. itching 3. xanthomas 4. too few bile ducts 5. biliary atresia 5. congenital heart problems (TOF)
6. posterior embryotoxon 7. unusual butterfly shape of one or more of the bones of the spinal column certain eye defects
8. narrowed pulmonary arteries 9. broad, prominent forehead 10. deep-set eyes 11. small pointed chin

Management:
1. Improve the heart function 2. reduce the effects of impaired liver, kidney, and spleen function
 Miscellaneous Association
• VACTERL Association:
V = Vertebral defects A = Anal atresia (imperforate anus) C = Cardiac defects (VSD and others) T = TE fistula E = Esophageal atresia
R = Renal defects L = Limb defects (radial)

• CHARGE Association:
C = Coloboma (from isolated iris to anophthalmos; retinal most common) H = Heart defects (TOF, PDA, and others)
A = Atresia choanae R = Retardation of growth and/or development G = Genital hypoplasia (in males)
E = Ear anomalies and/or deafness