Free USMLE Step 1 Human Development practice questions

Weeks 4 to 6 after fertilization fall within the embryonic period (weeks 3 to 8), the window of organogenesis. During these weeks the neural tube closes (week 4), the heart begins to beat and septates, the limb buds appear, and the face, ears and great vessels form. Cells are differentiating and migrating in tightly timed sequences, so a teratogen at this stage produces major structural malformations of whichever organs are forming at the time. This is the period of greatest sensitivity to structural birth defects.

Isotretinoin, a vitamin A analog, is among the most potent human teratogens. Exposure in this window causes craniofacial anomalies (microtia or anotia, small jaw, cleft palate), conotruncal heart defects and aortic arch anomalies, thymic hypoplasia, and CNS malformations such as hydrocephalus. The drug therefore requires two forms of contraception and repeated negative pregnancy tests.

A. Embryonic loss or normal development (the all-or-none effect) applies before week 3, when the embryo has not yet differentiated and surviving cells can replace damaged ones. C. Growth restriction without malformations is the typical result of exposures after week 8, in the fetal period. D. The embryo receives nutrients and drugs from maternal blood from implantation onward; uteroplacental circulation is established by about the end of week 3, and isotretinoin readily reaches the embryo. E. Isolated functional deficits, especially of the CNS, which keeps maturing, are characteristic of fetal period exposures; an exposure during organogenesis primarily causes structural defects.

Hematopoiesis moves through three sites during development. It begins in the yolk sac blood islands at about week 3, where primitive nucleated erythroblasts make embryonic hemoglobins (such as Gower 1, zeta2 epsilon2); yolk sac production ends by about week 8 to 10. From about week 6 the fetal liver becomes the main site and dominates through midgestation, producing definitive erythrocytes that contain fetal hemoglobin (alpha2 gamma2), with a smaller contribution from the spleen. Bone marrow hematopoiesis begins in the second trimester and becomes dominant in the last trimester, and after birth it is the only normal site. At 20 weeks, therefore, the liver is the predominant source. In severe fetal anemia, as in Rh hemolytic disease (maternal IgG anti-D destroying fetal cells), erythropoietin drives expansion of hepatic and splenic hematopoiesis. Hepatomegaly, along with reduced hepatic albumin synthesis, portal hypertension and high-output cardiac failure, contributes to hydrops fetalis, and nucleated red cells spill into the circulation. Later in life, marrow failure or ineffective erythropoiesis (myelofibrosis, beta-thalassemia major) can reactivate extramedullary hematopoiesis in the liver and spleen.

A. The yolk sac produces blood only during the embryonic period, ending well before 20 weeks. B. The spleen participates but contributes far less than the liver. C. The thymus is a site of T-cell maturation, not a primary hematopoietic organ for red cells. E. Bone marrow production starts in the second trimester but does not dominate until late gestation.

Daytime continence usually comes first, and nighttime dryness is the last milestone of bladder control. Many healthy 4-year-olds still wet the bed, and a meaningful minority of 5-year-olds do as well. For this reason the diagnosis of enuresis requires repeated voiding into the bed or clothes at least twice a week for at least 3 months in a child aged 5 or older. This boy is 4, is dry during the day, has a normal examination and urinalysis, and has a strong family history; nighttime wetting at his age is a normal developmental stage, best managed with reassurance.

When primary nocturnal enuresis persists beyond 5, it is usually a familial maturational delay in arousal to bladder fullness and in the nocturnal rise of ADH. The bed-wetting alarm gives the most durable cure, and desmopressin, a V2 agonist, works quickly but relapse is common. Encopresis has a lower age threshold of 4.

B. Central diabetes insipidus would cause polyuria and polydipsia day and night with dilute urine; a specific gravity of 1.020 shows normal concentrating ability.

C. Occult spinal dysraphism would usually cause daytime incontinence, abnormal gait or reflexes, or a sacral skin marker such as a dimple or hair tuft, none of which are present.

D. A urinary tract infection would cause dysuria, urgency or daytime accidents and an abnormal urinalysis.

E. Type 1 diabetes causes new wetting with polyuria, thirst and weight loss, with glucosuria on urinalysis.

Maternal IgG crosses the placenta by FcRn, mostly in the third trimester, and decays over the first months of life while the infant's own IgG production slowly rises. The result is a physiologic IgG nadir at about 3 to 6 months. In transient hypogammaglobulinemia of infancy, this nadir is deeper or prolonged: IgG stays below the age-specific range, sometimes with mildly low IgA, but B-cell and T-cell numbers are normal and, crucially, specific antibody responses to protein and conjugate vaccines are preserved. Infections are usually mild sinopulmonary ones, such as otitis, and growth is normal. The condition resolves on its own in early childhood, often by 2 to 4 years, so the diagnosis is confirmed in retrospect when IgG normalizes.

A. X-linked agammaglobulinemia (BTK) causes absent CD19 B cells, very low levels of all isotypes, absent tonsils and failure to make vaccine antibodies. B. Hyper-IgM syndrome (usually CD40 ligand deficiency) shows normal or high IgM with low IgG and IgA, poor class-switched vaccine responses and opportunistic infections such as Pneumocystis. C. Common variable immunodeficiency requires poor specific antibody responses and is rarely diagnosed before about age 4, because a transient infant nadir must be excluded. E. Severe combined immunodeficiency presents with failure to thrive, severe opportunistic infections and low T-cell counts.

Nasal hypoplasia and stippled epiphyses after first-trimester exposure to an INR-monitored oral anticoagulant are the features of fetal warfarin syndrome. Warfarin is still used in pregnancy in some women with mechanical valves, the setting where DOACs are contraindicated.

Warfarin inhibits vitamin K epoxide reductase (VKORC1). Reduced vitamin K is the cofactor for γ-glutamyl carboxylase, which adds γ-carboxyglutamate (Gla) residues to clotting factors and also to vitamin K-dependent bone and cartilage proteins such as osteocalcin and matrix Gla protein. Warfarin is small and lipid soluble, so it crosses the placenta. Exposure in weeks 6 to 12, when nasal and skeletal cartilage are forming, impairs carboxylation of these proteins and causes abnormal calcification, producing the embryopathy. Later exposure can cause CNS abnormalities and fetal hemorrhage.

A. Heparins potentiate antithrombin; they are large and highly charged, do not cross the placenta, and are preferred in pregnancy, but they are parenteral and are not monitored by the INR. B. Direct Xa inhibitors (rivaroxaban, apixaban) are avoided in pregnancy and with mechanical valves and are not followed by INR. C. Direct thrombin inhibitors such as dabigatran showed more valve thrombosis in mechanical valve patients and are not used here. E. Inhibition of thromboxane synthesis is the mechanism of aspirin, an antiplatelet drug that does not cause this embryopathy.

This boy is in a normal pubertal growth spurt: peak height velocity in boys comes late, around Tanner stage 4. Rising testosterone (and estrogen made from it by aromatase) amplifies GH pulses, and GH acts largely through IGF-1, made in the liver and locally by growth plate chondrocytes.

Longitudinal bone growth happens at the physis by endochondral ossification, and the cells are arranged from the epiphysis toward the metaphysis in sequence. Quiescent stem-like chondrocytes in the reserve zone feed the proliferative zone, where chondrocytes divide and stack into columns. This is the step that GH and IGF-1 stimulate and that FGFR3 restrains, so it sets the rate of lengthening. The cells then enlarge in the hypertrophic zone, the matrix mineralizes in the zone of calcification, and invading vessels bring osteoblasts that lay woven bone on the calcified cartilage in the zone of ossification. Estrogen eventually exhausts the proliferative capacity and fuses the plate.

A. The reserve zone contains quiescent chondrocytes that divide slowly; it supplies cells but is not the main site of IGF-1-driven proliferation.

B. Hypertrophic chondrocytes no longer divide; they enlarge, secrete type X collagen and VEGF, and form the weakest layer, through which Salter-Harris fractures and slipped capital femoral epiphysis pass.

C. In the zone of calcification the matrix mineralizes and chondrocytes die; failure here produces the wide, frayed physis of rickets.

D. The zone of ossification is where osteoblasts deposit bone on cartilage spicules; it does not contain dividing chondrocytes.

Normal pregnancy is a state of progressively increasing insulin resistance, most marked in the second and third trimesters. The main driver is human placental lactogen (hPL, also called human chorionic somatomammotropin), a GH- and prolactin-like hormone made by the syncytiotrophoblast. Its secretion rises in step with placental mass. hPL reduces maternal insulin sensitivity and promotes lipolysis, so the mother burns more free fatty acids and spares glucose, and both glucose and fatty acids flow to the fetus. This is a normal adaptation that guarantees fetal fuel.

Most women compensate by increasing insulin secretion. When beta-cell reserve is limited, as with obesity and a family history of type 2 diabetes, gestational diabetes results. Maternal hyperglycemia then crosses the placenta, fetal hyperinsulinemia follows, and the fetus grows large. Her normal first-trimester fasting glucose fits a problem that emerged as placental hormones rose.

A. hCG peaks at 8 to 10 weeks and then declines; it rescues the corpus luteum and does not drive the insulin resistance of later pregnancy.

B. Estriol is made from fetal adrenal DHEA-S and reflects fetal and placental well-being; it raises TBG, SHBG and clotting factors but is not the main diabetogenic hormone.

C. Inhibin A is a placental glycoprotein used in the quad screen; it does not regulate maternal glucose metabolism.

E. Relaxin, from the corpus luteum and placenta, softens connective tissue and contributes to renal vasodilation; it is not a major cause of insulin resistance.

Short stature with a normal growth velocity (a steady 5 cm per year along a consistent percentile), absent puberty at 14, an otherwise healthy boy, a normal sense of smell, normal thyroid and celiac studies, and a father who matured late are the classic picture of constitutional delay of growth and puberty, the most common cause of delayed puberty in boys and a variant of normal development.

The defining finding is a delayed bone age, typically about 2 years behind chronologic age and matching his height age. His gonadotropins are low for chronologic age but appropriate for bone age. Because the epiphyses remain open longer, he will keep growing after his peers stop, puberty will begin spontaneously, and adult height will be near his genetic target. Constitutional delay is a diagnosis of exclusion because early on it can resemble permanent hypogonadotropic hypogonadism.

B. High LH and FSH indicate primary gonadal failure, which would not explain short stature with a long-standing normal growth pattern.

C. Klinefelter syndrome (47,XXY) typically causes tall stature with long legs, small firm testes and gynecomastia, and puberty often begins and then stalls.

D. Hypoplastic olfactory bulbs characterize Kallmann syndrome, which causes anosmia; this boy smells normally, and Kallmann patients tend toward eunuchoid proportions.

E. GH deficiency causes short stature with a slow growth velocity that crosses percentiles downward, unlike his steady growth.

Pruritic rash, nonpurulent conjunctivitis, low fever, and arthralgia in early pregnancy followed by fetal severe microcephaly with subcortical calcifications is congenital Zika syndrome. Zika is a flavivirus whose main vector is the Aedes mosquito, but unlike other arboviruses it is also transmitted sexually, vertically, and by transfusion.

This woman never traveled, lives where Aedes mosquitoes do not circulate in January, and received no blood products. Her husband, however, had a compatible illness in an endemic region shortly before she became ill. Zika RNA persists in semen for months, so sexual transmission from a returning partner is the most likely route. This is why returning travelers are advised to use condoms or abstain during a partner's pregnancy. Neural progenitor cells in the developing cortex are a major target of the virus, explaining microcephaly; Zika can also cause Guillain-Barre syndrome in adults.

A. Culex mosquitoes transmit West Nile and St. Louis encephalitis viruses, not Zika, and are inactive in a Minnesota winter. B. Zika is not spread by respiratory droplets. C. Transfusion transmission occurs but she received no blood products. E. Aedes mosquitoes are the usual vector, but they are not present in Minnesota in January and she did not travel, so a mosquito bite cannot explain her infection.

Each partner has α-thalassemia trait from a cis deletion (--/αα): both α-globin genes are missing from one chromosome 16, and the partner chromosome is normal. The clues for thalassemia trait rather than iron deficiency are microcytosis out of proportion to the anemia, a high RBC count (Mentzer index 66/5.6, about 12), normal ferritin and no response to iron. Adult electrophoresis is normal in α-thal trait because HbA2 and HbF are not raised, so DNA testing is needed.

At meiosis each parent passes either the empty chromosome (--) or the normal one (αα), each with a probability of 1/2. A fetus with no α genes (--/--) must receive the empty chromosome from both parents: 1/2 × 1/2 = 1/4, or 25%. That fetus has Hb Barts hydrops fetalis. Of the remaining pregnancies, 50% will be cis carriers like the parents and 25% will have four normal genes. Cis deletions are common in Southeast Asian populations, which is why Hb Barts hydrops clusters there.

A. 0% would be correct for trans deletions (-α/-α), typical of African ancestry, because each parent always transmits one working α gene. B. 12.5% does not correspond to any Mendelian outcome for two heterozygous parents of a single locus. D. 50% is the chance that a child will inherit the cis carrier state, not the chance of losing all four genes. E. 100% would require both parents to have no normal chromosome 16, which is incompatible with their mild phenotype.