Peds Genetic Disorders

Screening in African ancestry

SCD

Screening in Mediterranean basin

Thalassemia

Pre-natal genetic assessment (invasive)

Amniocentesis, chorionic villus sampling

Pre-natal genetic assessment (non-invasive)

Ultrasound

AFP

Quad screen during 2nd trimester

AFP increased vs. decreased

Increase -> NTDs, gastroschisis, omphalocele

Decreased -> trisomy 21/13/18

Quad screen

AFP, unconjugated estrial, HCG and inhibin A

*during second trimester

Newborn screening

All states mandate metabolic screening between 24 and 48 hours of life in hospital (infant must be fed first)

Teratogenic infections

TORCH

Toxoplasmosis

Other - varicella, Zika, syphillis

Rubella

Cytomegalovirus

Herpes simplex

Teratogenic meds

AEDs, retinoids

Teratogenic substances

Alcohol, smoking, radiation

Child presents with flat facial profile, upward slanted palpebral fissures, flat nasal bridge w epicanthal folds, a gap between the 1st and 2nd toes, and a small mouth w protruding tongue. What is suspected

Trisomy 21

MC autosomal chromosomal abnormality

Trisomy 21

*3 complete or partial copies of CS21

Trisomy 21 clinical features

Hypotonia -> poor weight gain

Increased risk of autism

Cardiac defects

GI anomalies

Hypothyroidism

Risk of leukemia, Alzheimer's

1 mo old presents w prominent occiput, narrow bifrontal diameter of forehead, low-set malformed ears, rocker bottom feet and congenital heart disease (VSD, ASD, PDA)

Trisomy 18

Trisomy 18

three copies of chromosome 18, associated w advanced maternal age

Adolescent child presents w short stature, webbed neck, aortic stenosis, and a shield-shaped chest. What do you suspect?

Turner syndrome

Turner syndrome

A single X chromosome -> susceptible to X linked disorders

Turner syndrome tx

GH, estrogen/progesterone replacement

Adolescent 6 ft male presents with delayed puberty, gynecomastia, small phallus and testes, arm span greater than high, lower IQ. What do you suspect?

Kleinfelter syndrome

Kleinfelter syndrome

MC genetic cause of hypogonadism and infertility in men

Kleinfelter syndrome tx

Testosterone therapy during puberty

Pt comes into clinic w a short stature & proportionally large head, their digits are short and stubby, kyphoscoliosis, prominent forehead with frontal bossing and depressed nasal bridge. What do you suspect?

Achondroplasia

Achondroplasia

autosomal dominant, dwarfism

- skeletal dysplasia, disorder of cartilage calcification, linked to Cs4

Associated w advanced PATERNAL age

Achondroplasia medical issues

Hydrocephalus, central apnea

Bowed legs

Dental malocclusion

Hearing loss

Compression of nerve roots and sciatica

Achondroplasia tx

Conjugated C-type natriuretic peptide

Adaptive modifications

Pt presents w short stature, blue sclera, bowed legs, and frequent fractures w minimal trauma. What do you suspect?

Osteogenesis imperfecta

osteogenesis imperfecta tx

Bracing, biphosphonates if severe

Pt presents w absent thymus, cleft palate, micrognathia, tetralogy of fallot, hypertelorism. Hx reveals recurrent pyogenic infections (OM, sinusitis, tonsillitis, PNA). What do you suspect?

22Q11 deletion syndrome

Pt presents w macroorchidism w testicular edema, dysmorphic facial features (large jaw and ears), cognitive impairment, and behavioral issues. Hx reveals that had a large body habitus at birth. What do you suspect?

Fragile X syndrome

Fragile X syndrome

X-linked form of intellectual disability

- FRAX gene

Patient presents with narrow bifrontal diameter, down-turned mouth, small hands and feet, short stature, hypogonadism, and an uncontrollable appetite. What do you suspect?

Prader-Willi syndrome

Prader-Willi Syndrome

Insertional deletion on chromosome 15q11

Pt presents w hepatomegaly, direct hyperbilirubinemia, acidosis, glycosuria, emesis, anorexia, poor growth, cataracts, and severe learning disabilities. What is suspected

Galactosemia

MC carbohydrate metabolism disorder

Galactosemia

*autosomal recessive, can be identified by newborn screen

Galactosemia

inability to metabolize galactose -> galactose 1-phosphate accumulates in liver, kidney, brain

Galactosemia management

Dx must be made in first week of life

DNA testing confirms dx

Tx -> NO BREAST MILK (eliminate galactose/lactose)

1 yr old pt presents w moderate-severe intellectual disability, hypertonia, tremors, pale skin, behavioral issues, and mouse-like odor in urine. What is suspected?

Phenylketonuria

MC amino acid metabolism disorder

phenylketonuria

- inability to catabolize amino acids from protein -> build up in brain, eye, skin, or liver

Phenylketonuria

deficiency of phenylalanine hydroxylase; converts phenylalanine into tyrosine; resulting seizures and mental retardation can be prevented by dietary modification

Phenylketonuria management

Early detection through newborn screen -> lifelong restriction of phenylalanine

Restriction of phenylalanine within first 10 days of life -> normal IQ

Disorder of mitochondrial energy metabolism

Pyruvate dehydrogenase deficiency, deficiencies of respiratory chain components

Sx of mitochondrial disease

FTT

Hypotonia

Cardiomyopathy

Seizures

Hypoglycemia

Developmental regression

Mitochondrial disease management

Muscle biopsy -> ragged red fiber

Tx: vitamin cofactors for respiratory chain and coenzyme Q10, ketogenic diet