Human Growth and Development Quiz

Growth Disorders

• Human growth is a continuous, though not linear, process, divided into infantile, childhood, and pubertal phases, each with distinct patterns. Timing and speed of growth differ between boys and girls, especially during puberty.
• Intrauterine growth is primarily influenced by maternal nutrition and placental factors. Insulin plays a role by stimulating IGF1/2 production. A newborn's typical length is around 50 cm.
• Infantile phase (first two years): Growth is initially rapid, then decelerates. Typical growth during this period is 25 to 30 cm.
• Childhood phase (3 years to adolescence): Growth is relatively constant at 5 to 7 cm per year, with some slowing in later childhood.
• Pubertal phase: Characterized by a growth spurt, typically 8 to 14 cm per year. Increased gonadal steroids (testosterone and estrogen) and growth hormone (GH) synergistically drive this growth, along with IGF-1.
• The growth plate is crucial for longitudinal growth.
• Serial growth measurements are vital for monitoring child health. Normal growth patterns suggest good health; slower-than-normal growth may indicate underlying illness, including hormonal issues.
• Auxological parameters (height/length, weight, BMI) are fundamental for assessing potential short stature.

Measurement of Growth

• Newborn measurements (length, weight, head circumference) are crucial, compared to gestational age.
• Infantometer is used to measure newborns and infants.
• Children over two years are measured by height, weight, and head circumference, corresponding to their gender. Stadiometer is used for standing measurements.
• WHO international growth charts (2006) are recommended for children under two; local charts are used for older children.
• Normal height is based on age, sex, ethnicity, and family context. Target height is calculated based on parental heights (differing calculations for boys and girls).

Short Stature

• Short stature is defined as a height 2 standard deviations below the mean for the same age, sex, and ethnic group (or below the 3rd percentile). Common causes include familial factors or constitutional delay.
• Growth failure is a growth rate below normal.
• Short stature is a frequent reason for referral to pediatric endocrinologists, with an incidence of 3-5%.
• Growth hormone deficiency prevalence is around 1 in 4000.

Classification

• Proportionate short stature: Limbs are proportionate to the trunk, often familial.
• Disproportionate short stature: Limbs are disproportionately shorter than the trunk, associated with skeletal dysplasia.

Etiology of Short Stature

• Unknown origin (Idiopathic short stature): Accounts for ~80% of cases, including familial and constitutional short stature. Constitutional short stature arises from delayed puberty.

• Prenatal origin:

• Disproportionate SS: osteochondrodysplasia (e.g., achondroplasia, hypochondroplasia - FGFR3 gene mutations), osteogenesis imperfecta (collagen 1 gene mutations), SHOX gene-related conditions (e.g., Leri-Weill dyschondroosteosis, Langermesomelic dysplasia).

• Proportionate SS: Silver-Russell syndrome (IUGR, feeding problems, triangular face, clinodactyly), Turner syndrome (45XO), Noonan syndrome (autosomal dominant, "male Turner syndrome"), Prader-Willi syndrome (SNPRN and Necdin gene defects, hypotonia, severe obesity).

• Congenital growth hormone deficiency

• Small for gestational age (SGA): Birth weight and/or length are 2 standard deviations below the mean for gestational age. Most SGA children experience catch-up growth in the first and second year.

• Postnatal origin:

• Endocrine disorders: Growth hormone deficiency, hypothyroidism, chronic hypercortisolism (including glucocorticoid use), sex steroid excess, pseudohypoparathyroidism.

• GI disorders: Inflammatory bowel disease, celiac disease.

• Renal disorders: Chronic kidney disease.

• Pulmonary disorders: Asthma, cystic fibrosis. Postnatal short stature is not usually due to GH deficiency, but rather related organ pathologies.

Growth Hormone Deficiency

• Congenital: Presents in newborns (hypoglycemia in some forms), toddlers/preschoolers with lifelong short stature, doll-like facies, truncal obesity, and brachydactyly.
• Acquired: Results from trauma, tumors (craniopharyngeoma), or autoimmune conditions.

Diagnosis of Short Stature

• History (perinatal, family).
• Physical exam (auxological parameters, pubertal stage).
• Growth pattern analysis.
• X-ray of left hand and wrist (bone age).
• Laboratory tests (CBC, CRP/ESR, biochemical markers, renal/liver/thyroid tests, urinalysis).

Tests to Confirm GH Deficiency:

• IGF-1 measurement.
• Stimulation tests (insulin tolerance test, clonidine test, glucagon test). MRI of pituitary for follow up.
• Treatment: addressing underlying causes and, potentially, recombinant GH therapy.

Achondroplasia

• Common skeletal dysplasia, caused by FGFR3 gene mutation. It has variable inheritance patterns.
• Characteristics include short stature, macrocephaly, prominent brow, midface retrusion, flattened nose, and spinal curvature abnormalities.
• Average height for adults (males ~131cm, females ~124cm).
• Treatment includes GH treatment.

Osteogenesis Imperfecta

• Genetic disorder causing type I collagen deficiency impacting bone formation.
• Features include brittle bones, fractures from minimal trauma, blue sclerae, joint laxity, hearing loss, and opalescent teeth.
• Treatment is supportive, focusing on managing fractures; IV bisphosphonates may be used.

Turner Syndrome

• Condition with complete absence of one X chromosome (45,X).
• Features include short stature, ovarian failure, congenital heart defects (CoA), kidney anomalies (horseshoe kidney), webbed neck, broad chest, wide-set nipples, low-set ears, and neonatal lymphedema.

Prader-Willi Syndrome

• Microdeletion syndrome (15q11-13) resulting in hypotonia, feeding problems, dolichocephaly, small mouth, hypogonadism, short stature, hyperphagia, severe obesity, intellectual disability, and temperament issues.

Chronic Glomerulonephritis

• Chronic GN can have few symptoms initially, presenting as asymptomatic hematuria or proteinuria.
• It may be preceded by acute nephritic syndrome. Causes could be primary (e.g., IgA nephropathy) or secondary (e.g., lupus nephritis).

IgA Nephropathy (Berger Disease)

• Most common primary GN. Frequently affects males. Etiology is unknown, but hypothesized to be related to circulating IgA antibody defects.
• Highly variable course. Can involve asymptomatic stages, recurring episodes of gross hematuria with flank pain/fever following infections ("synpharyngitic hematuria"). Can lead to rapid progression to RPGN and/or nephrotic syndrome (~10%) and ESRD (~50%).
• Diagnosis is based on clinical presentation, urinalysis (hematuria, proteinuria), serum IgA levels(sometimes elevated), and biopsy (mesangial proliferation, IgA deposits).
• Differentiate from post-streptococcal GN (low complement levels, 10-20 days after infection), lupus nephritis, or MPGN.
• Treatment includes monitoring, ACE inhibitors/ARBs, and, for severe cases, glucocorticoids plus immunosuppressants.

Henoch-Schönlein Purpura (HSP)

• Acute immune complex-mediated small vessel vasculitis, most common in children (~90% under 10 yrs).
• Typically presented by a tetrad of symptoms: palpable purpura, arthritis/arthralgia, abdominal pain, and renal disease. Often preceded by an upper respiratory infection (1-3 weeks prior).
• Diagnosis is based on clinical presentation, and laboratory tests (CBC, coagulation, serum antibodies, urinalysis). Biopsy is potentially required in complex cases, for confirmation and to assess severity of presentations (skin showing leukocytoclastic vasculitis with IgA and C3 deposits, kidney biopsy showing mesangial IgA and possible crescents).
• Differentiate from other causes of purpura, arthritis, and renal involvement.
• Treatment is typically supportive, with pain management and regular follow-up. Severe cases can require hospitalization and systemic glucocorticoids.

Alport Syndrome

• Genetic disorder caused by a defect in type IV collagen, primarily inherited as an X-linked recessive trait.
• Often presents with asymptomatic hematuria in infancy.
• Characterized by progressive glomerulonephritis, leading to ESRD (typically in adolescence-early adulthood), sensorineural hearing loss, and sometimes eye abnormalities (lenticonus).
• Diagnosis involves urinalysis, molecular genetic testing, and potentially renal biopsy (LM/EM showing "basket-weave" appearance).
• Treatment involves monitoring renal function, and potentially ACE inhibition, hearing aids, and surgical corrections (if needed).

Antibiotic Therapy in Children

• Empiric vs. targeted therapy.
• Prophylactic therapy is used to prevent infections in immunosuppressed patients, before/after surgery, or in post-exposure situations.
• Empiric therapy is used for life-threatening or severe infections, before the causative organism is known. Specific empirical therapy suggestions based on suspected site and potential pathogens. Factors influencing antibiotic choice include the suspected infection site (upper vs. lower respiratory tract and other considerations), host factors (immunosuppression, geographical location, and pre-existing conditions), and drug factors (resistance, side effects).
• Contraindications/specific considerations in pediatric antibiotic use exist for various types of antibiotics (e.g., aminoglycosides).