28.4 Pediatric Oncology & Genetics: Leukemias and Lymphomas, Retinoblastoma, Wilms Tumor, Neuroblastoma, Ewing Sarcoma and Osteosarcoma; Sex Chromosome and Autosomal Disorders, Inborn Errors of Metabolism and the Dysmorphic ("Odd-Looking") Child

Why this area matters

The TOS oncology and genetics competencies are to:

• identify the age, sex and racial predilection of these disorders and their mortality and morbidity;
• reach a diagnosis from history and examination, with a differential diagnosis;
• prioritize tests;
• plan drug and surgical management;
• educate the family.

Childhood cancer is highly curable when diagnosed early and treated in a specialized center. Many Filipino children still present late or abandon treatment because of cost and distance. The National Integrated Cancer Control Act (RA 11215) includes children's cancer services.

Warning signs of childhood cancer:

• persistent unexplained fever, pallor or bruising;
• bone pain or limping;
• a lump or abdominal mass;
• leukocoria or a new squint;
• morning headache with vomiting;
• unexplained weight loss.

Leukemias and lymphomas

• Acute lymphoblastic leukemia (ALL):
  • the most common childhood cancer, peaking at 2 to 5 years;
  • marrow failure causes pallor, fever and infections, and bruising and petechiae;
  • infiltration causes bone pain (limping, refusal to walk), lymphadenopathy, hepatosplenomegaly, testicular enlargement and CNS disease;
  • T-cell ALL causes a mediastinal mass with airway compression;
  • the CBC shows cytopenias with or without blasts, and bone marrow aspiration confirms it;
  • the main risk at diagnosis is tumor lysis syndrome: hyperkalemia, hyperuricemia, hyperphosphatemia and hypocalcemia, prevented with hydration and allopurinol or rasburicase;
  • good prognostic factors: age 1 to 10 years, WBC below 50,000/uL, B-cell type, hyperdiploidy or t(12;21), and rapid early response;
  • cure rates exceed 80% to 90% with modern protocols.
• Acute myeloid leukemia is less common and harder to cure. It shows Auer rods, chloromas and gum infiltration, and DIC in the promyelocytic type. Down syndrome raises the risk of both ALL and AML.
• Lymphomas:
  • Hodgkin lymphoma: adolescents with painless cervical or mediastinal nodes, B symptoms and Reed-Sternberg cells.
  • Non-Hodgkin lymphoma: rapidly growing.
  • Burkitt lymphoma: t(8;14), c-MYC, a "starry-sky" pattern; in the abdomen it can present as intussusception; the endemic jaw form is linked to EBV. Very fast growth means a high risk of tumor lysis.

Solid tumors

Chromosomal and sex chromosome disorders

• Down syndrome (trisomy 21):
  • the most common chromosomal cause of intellectual disability; risk rises with maternal age;
  • features: hypotonia, flat facial profile, upslanting palpebral fissures, epicanthal folds, small ears, Brushfield spots, single palmar crease and a sandal gap;
  • atrioventricular septal defect, duodenal atresia, Hirschsprung disease, hypothyroidism, atlantoaxial instability, leukemia and early Alzheimer disease;
  • usually nondisjunction (95%); translocation cases need parental karyotyping.
• Edwards syndrome (trisomy 18): clenched hands with overlapping fingers, rocker-bottom feet, a prominent occiput, VSD; most die in infancy.
• Patau syndrome (trisomy 13): cleft lip and palate, holoprosencephaly, polydactyly, scalp defects (cutis aplasia), microphthalmia.
• 22q11.2 deletion (DiGeorge): conotruncal defects, hypocalcemia, immunodeficiency and cleft palate.
• Turner syndrome (45,X):
  • short stature, webbed neck, lymphedema of hands and feet at birth, shield chest;
  • coarctation and bicuspid aortic valve, horseshoe kidney;
  • streak ovaries with primary amenorrhea and no puberty;
  • normal intelligence;
  • treated with GH and estrogen.
• Klinefelter syndrome (47,XXY): tall stature, small firm testes, gynecomastia, infertility, learning difficulties, hypergonadotropic hypogonadism. Treated with testosterone at puberty.
• Fragile X syndrome: the most common inherited cause of intellectual disability in boys. CGG repeat expansion causes a long face, large ears, macroorchidism after puberty and autistic features.

Inborn errors of metabolism

When to suspect an inborn error:

• a previously well newborn who deteriorates after feeding;
• unexplained metabolic acidosis, hypoglycemia or hyperammonemia;
• an unusual odor;
• developmental regression;
• consanguinity.

The dysmorphic ("odd-looking") child

• History: pregnancy exposures (alcohol, drugs, infections), family history and pedigree, and developmental history.
• Measurements: growth parameters and head size.
• Look for anomalies:
  • minor anomalies, such as low-set ears, a single palmar crease and widely spaced eyes;
  • three or more minor anomalies raise the chance of a major anomaly, such as of the heart or kidneys, so look for one.
• Recognizable patterns: fetal alcohol syndrome (smooth philtrum, thin upper lip, short palpebral fissures, growth deficiency, neurodevelopmental problems).
• Investigations: karyotype, chromosomal microarray and targeted gene or exome testing.
• Genetic counseling covers recurrence risk.