A 1-year-old boy presents to pediatrics clinic for a well-child visit. He has no complaints. He has a cleft palate and an abnormal facial appearance. He has been riddled with recurrent infections and is followed by cardiology for a ventricular septal defect (VSD). Vital signs are stable, and the patient's physical exam is benign. If this patient's medical history is part of a larger syndrome, what might one also discover that is consistent with the manifestations of this syndrome?

Hypoactive deep tendon reflexes

A 14-year-old boy presents as a new patient to your practice. While conducting your physical exam, you observe the findings depicted in Figures A and B. Which of the following additional findings would most likely be found in this patient?

A white tuft of scalp hair since birth

A family history of seizures and intellectual disability

A 5-year-old boy is brought to the physician because of behavioral problems. His mother says that he has frequent angry outbursts and gets into fights with his classmates. He constantly complains of feeling hungry, even after eating a full meal. He has no siblings, and both of his parents are healthy. He is at the 25th percentile for height and is above the 95th percentile for weight. Physical examination shows central obesity, undescended testes, almond-shaped eyes, and a thin upper lip. Which of the following genetic changes is most likely associated with this patient's condition?

Loss of paternal gene expression on chromosome 15

Mitotic nondisjunction of chromosome 21

Mutation of FBN-1 gene on chromosome 15

Microdeletion of long arm of chromosome 7

Deletion of Phe508 on chromosome 7

An infant boy of unknown age and medical history is dropped off in the emergency department. The infant appears lethargic and has a large protruding tongue. Although the infant exhibits signs of neglect, he is in no apparent distress. The heart rate is 70/min, the respiratory rate is 30/min, and the temperature is 35.7°C (96.2°F). Which of the following is the most likely cause of the patient’s physical exam findings?

Congenital agenesis of an endocrine gland in the anterior neck

Autosomal dominant mutation in the SERPING1 gene

Genetic imprinting disorder affecting chromosome 11p15.5

Type I hypersensitivity reaction

Excess growth hormone secondary to pituitary gland tumor

A 5-year-old boy presents for a regularly scheduled check-up. The child is wheelchair bound due to lower extremity paralysis and suffers from urinary incontinence. At birth, it was noted that the child had lower limbs of disproportionately small size in relation to the rest of his body. Radiograph imaging at birth also revealed several abnormalities in the spine, pelvis, and lower limbs. Complete history and physical performed on the child's birth mother during her pregnancy would likely have revealed which of the following?

Uncontrolled maternal diabetes mellitus

An 8-year-old child with “elfin” facial features is very friendly with strangers. He has a history of mild mental retardation, and a hemizygous deletion on chromosome 7q11.23, that includes a portion of the elastin gene. Which of the following is most likely true in this patient?

Symptoms may develop secondary to left ventricular outflow tract obstruction

Vitamin D supplementation is recommended

This patient is less likely to experience angina

Holosystolic murmur heard at the apex with radiation to the axilla

Carpopedal spasm induced by sphygmomanometer inflation

A 1-week-old baby is brought to the pediatrician’s office for a routine checkup. On examination, she is observed to have microcephaly with a prominent occiput. She also has clenched fists and rocker-bottom feet with prominent calcanei. A cardiac murmur is evident on auscultation. Based on the clinical findings, a diagnosis of nondisjunction of chromosome 18 is suspected. The pediatrician orders a karyotype for confirmation. He goes on to explain to the mother that her child will face severe growth difficulties. Even if her daughter progresses beyond a few months, she will not be able to reach developmental milestones at the appropriate age. In addition to the above, which of the following is most likely a consequence of this genetic disturbance?

Death within the first year of life

Multiple malformation syndromes for USMLE Step 2 CK: High-Yield Pediatrics Lessons

Intro & Associations - Alphabet Soup Syndromes

Non-random clustering of malformations without a single, defined unifying cause.
Represents associations, not sequences or syndromes with known chromosomal/gene defects (exception: CHARGE).

Mnemonic	Features
VACTERL	Vertebral, Anal atresia, Cardiac, Tracheo-Esophageal fistula, Renal, Limb
CHARGE	Coloboma, Heart defects, Atresia choanae, Retardation (Growth), Genital hypoplasia, Ear anomalies
MURCS	Müllerian duct, Renal & Cervicothoracic Somite abnormalities

CHARGE Syndrome: Facial features, coloboma, ear abnormality

Common Trisomies - Triple Chromosome Trouble

Syndrome	Chromosome	Key Features
Down Syndrome	Trisomy 21	📌 Drinking age at 21. Flat facies, single palmar crease, sandal gap, Brushfield spots, duodenal atresia, endocardial cushion defect. Intellectual disability.
Edwards Syndrome	Trisomy 18	📌 Election age at 18. Micrognathia, low-set ears, clenched hands (overlapping fingers), rocker-bottom feet. Congenital heart defects (VSD).
Patau Syndrome	Trisomy 13	Midline defects: Holoprosencephaly, microphthalmia, cleft lip/palate, polydactyly, cutis aplasia (scalp defects). Severe intellectual disability.

Microdeletions - Key Genetic Gaps

DiGeorge Syndrome (22q11.2 deletion):
- 📌 CATCH-22: Cardiac defects (ToF), Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia.
- Defective 3rd/4th pharyngeal pouch development.
Williams Syndrome (7q11.23 deletion):
- "Elfin" facies, intellectual disability, extreme friendliness.
- Supravalvular aortic stenosis, transient hypercalcemia.
Prader-Willi & Angelman (15q11-q13 deletion):
- Prader-Willi: Paternal deletion. Neonatal hypotonia, hyperphagia, obesity.
- Angelman: Maternal deletion. "Happy puppet," seizures, ataxia.
Cri-du-chat Syndrome (5p deletion):
- High-pitched, cat-like cry.
- Microcephaly, hypertelorism.

⭐ High-Yield Fact: Fluorescence In Situ Hybridization (FISH) is the gold-standard diagnostic test for detecting microdeletions, as they are often too small for standard karyotyping.

Neurocutaneous Syndromes - Skin & Brain Clues

Also known as Phakomatoses, these genetic disorders affect the skin, nervous system, and other organs.

Syndrome	Gene	Skin Manifestations	CNS & Ocular Manifestations
Neurofibromatosis 1	NF1 (Chr 17)	Café-au-lait spots (>6), Axillary/inguinal freckling, Neurofibromas	Optic Glioma, Lisch nodules (iris hamartomas)
Neurofibromatosis 2	NF2 (Chr 22)	Fewer skin signs	Bilateral Vestibular Schwannomas, Juvenile cataracts
Tuberous Sclerosis	TSC1/TSC2	Ash-leaf spots (hypopigmented), Shagreen patch, Adenoma sebaceum	Cortical tubers, Subependymal Giant Cell Astrocytoma (SEGA)
Sturge-Weber Syndrome	GNAQ (Somatic)	Port-wine stain (V1/V2 distribution)	Leptomeningeal angioma, Glaucoma, Tram-track calcifications

📌 Mnemonic for Tuberous Sclerosis: HAMARTOMAS (Hamartomas, Angiofibromas, Mitral regurgitation, Ash-leaf spots, Rhabdomyoma, TSC, Autosomal dominant, Mental retardation, Shagreen patch).

⭐ For Neurofibromatosis type 1, the diagnosis requires ≥2 of the key clinical features (e.g., ≥6 café-au-lait macules, ≥2 neurofibromas, axillary freckling, optic glioma, etc.).

High‑Yield Points - ⚡ Biggest Takeaways

VACTERL is a non-random association of defects, not a true syndrome.

CHARGE syndrome is linked to CHD7 gene mutations; key features are coloboma and choanal atresia.

DiGeorge syndrome (22q11.2 deletion) causes CATCH-22 findings: cardiac anomalies, thymic aplasia, and hypocalcemia.

Trisomy 18 (Edwards) shows clenched hands with overlapping fingers and rocker-bottom feet.

Trisomy 13 (Patau) is marked by severe midline defects like holoprosencephaly.

Beckwith-Wiedemann syndrome presents with macrosomia, macroglossia, and omphalocele, with a risk of Wilms' tumor.

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