Genetics Dysmorphology in Pediatrics - MedicoNotes
Genetics Dysmorphology in Pediatrics - MedicoNotes
Genetics Dysmorphology in Pediatrics - MedicoNotes
Trisomy Syndromes
Down (Trisomy 21) Edward (Trisomy 18) Patau (Trisomy 13)
CNS 1- Mental Retardation 1- Mental Retardation 1- Holoprosencephaly
1- Brushfield spots 1- Microcephaly 1- Microcephaly
2- Upslanting palpebral fissure. 2- Micrognathia 2- Microophthalmia
Facial defects 3- Inner epicanthic folds 3- Prominent occiput 3- Ocular hypotelorism
4- Microganthis &Tongue protrusion 4- Low set malformed ears 4- Bulbous nose
5- Low set small ear 5- Low set malformed ears
6- Delayed fontanel closure 6- Cleft lip/palate
1- Hypotonia 1- Closed fist with : index finger
2- Simian crease overlapping the 3rd digit & 1- Flexed fingers
Extremities 3- short and broad hands 5th digit overlapping the 4th 2- with Polydactyly
4- Hypoplasia of the middle 2- Rocker bottom feet
phalanx of the 5th finger & Hammer toe
Cardiac 1- Endocardial Cushion Defect (MOST COMMON) lead to PH 1- VSD MOST COMMON 1- VSD
(major cause of early mortality) 2- VSD > PDA , ASD , MVP 2- ASD 3- PDA 2- ASD 3- PDA
1- Duodenal atresia 2- Esophageal atresia 3- Pyloric stenosis Omphalocele
GIT 4- Hirschbrung disease 5- Malrotation of bowel
1- Polycystic kidney 1- Polycystic kidney
Renal 2- Ectopic and double ureter
1- Acute Lymphocytic Leukemia (ALL)
2- Early onset Alzheimer's disease Prognosis is Very poor, 95% die <1 year of age 1- Single umbilical artery
3- Atlantoaxial instability: ( 10% - 15% Progress over several weeks)
- due to excessive laxity in the posterior transverse ligament
Complications causes increased mobility between atlas (C1) and the axis (C2) :
a- Behavioral changes b- Torticollis c- urinary incontinence
d- Vertebrobasilarsymptoms : dizziness, vertigo, diplopia.
Risk factor: Advanced e- On examination, upper motor neuron symptoms such as :
maternal age >35 years leg spasticity, hyperreflexia, a positive Babinski sign, clonus
- X-ray: Diagnosed with lateral radiographs of the cervical spine
in flexion, extension, and in a neutral position
- TTT: surgical fusion of (C1) to the (C2).
Sex Chromosome Abnormalities
Turner syndrome (45XO or mosaicism) Noonan syndrome Klinefelter syndrome (47XXY)
Sporadic / Not related to advanced maternal age Not related to advanced maternal age Risk factor: Advanced maternal age
Phenotypically Female with : - Autosomal dominant. - Presence of an extra X chromosome in males (1:500)
1- Short stature
- Phenotypically similar to Turner syndrome but can affect both sexes. - Most common cause of hypogonadism and infertility in males
2- Craniofacial abnormalities: (protruding ears, neck webbing ,
Description low occipital hairline, high arched palate) - Girls with Noonan syndrome have normal XX chromosomes. 1-Tall and thin body
3- Endocrine: Primary Hypothyroidism - Pulmonary stenosis. 2- Gynecomastia + Female hair distribution
4- Chest: Shield shaped thorax / widely spaced nipples 3- Testicular atrophy: Small testes but puberty occurs at normal age
- Mental retardation often present.
5- Cardiac defects : Coarctation of the aorta + biscuspid aortic valve 4- Azoospermia
6- Reproduction: Ovarian dysgenesis Infertility 5- Mild mental retardation + Psychosocial adjustment abnormalities
7- Renal Anomalies: Horseshoe Kidney, double renal pelvis (U/S)
Diagnosis:
Treatment: (give estrogen/ growth hormone / anabolic steroid) Testosterone levels: Hypogonadism & Hypogenitalism
Patients at higher risk of osteoporosis due to :
a- lower estrogen levels ttt: give Estrogen Treatment:
b- & only having one copy of X chr. genes involved in bone metabolism Replace testosterone at 11-12 years of age
Other Syndromes
Fragile X syndrome - The syndrome results from: a ful lmutation in the FMR 1 gene caused by an increased number of CGG trinucleotide repeats accompanied by aberrant methylation of the FMR 1 gene.
Most common cause of Mental - Affected males of Fragile X syndrome have 3 LARGE : 1- Macrocephaly (Large Head)+ long face,prominent forehead 2- Large protruding ears 3- Large testes
Retardation in boys Behavioral: 1- Attention Deficit Hyperactivity Syndrome 2- Autism
- Infant with Multiorgan Enlargement: D.D: Congenital hypothyroidism
Beckwith-Wiedemann 1- Macrosomia 2- Macroglossia 3- Pancreatic B-cell hyperplasia: Hypoglycemia & Hyperinsulinemia Presents with :
syndrome 4- Visceromegaly 5- Omphalocele 5- Microcephaly 1- Hypotonia
- Usually sporadic BUT - Additional features include: 1- Prominent eyes 2- Prominent occiput 3- Ear creases 2- Macroglossia
- Some involving familial inheritance - Complications: 3- Umbilical hernia Instead of omphalocele.
1- Hypoglycemia may be severe and intractable TTT: subtotal pancreatectomy may be needed. 4- Head circumference of patients with congenital hypothyroidism may be increased
Associated with duplication of whereas patients with Beckwith syndrome have microcephaly.
chromosome 11 p (Encoding for IGF-2)
2- Patients have an increased risk of neoplasms such as: Wilms' tumor, Hepatoblastoma, Gonadoblastoma
- Obtain U/S & serum AFP every 6 months through 6 years of age to look for Wilm's Tumor/Hepatoblastoma 5- NO Hypoglycemia and hyperinsulinemia.
- Sporadic: defect in the G-prote in cAMP-kinase function in the affected tissue thereby resulting in autonomous activity of that tissue.
McCune-Albright - It is a rare condition characterized by 3P: 1- Precocious puberty 2- Pigmentation: cafe au lait spots 3- Polyostotic fibrous dysplasia (multiple bone defects).
syndrome - It is responsible for 5% of the cases of female precocious puberty,
- may be associated with other endocrine disorders, as : 1- Hyperthyroidism, 2- Prolactin- or GH-secreting pituitary adenomas 3- Adrenal hypercortisolism.