A 3-year-old boy is brought to the office due to delayed milestones. Over the past year, the patient has been receiving physical and speech therapies for delays in language and gross motor skills. He can walk up and down stairs and run well but cannot pedal a tricycle. Vocabulary includes approximately 25 words, and the patient does not speak in sentences. The parents say that he has poor eye contact and shows no interest in engaging with other children. Vaccinations are up to date. The patient has an uncle with Down syndrome. Head circumference, length, and weight are all at the 5th percentile. Examination of the face shows small palpebral fissures, an indistinct nasal philtrum, and midface hypoplasia. The lungs are clear to auscultation, and a 2/6 systolic ejection murmur is heard loudest at the left lower sternal border while the child is lying down. Which of the following is the most likely etiology of this patient's presentation?
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This patient's facial features, delayed development (ie, inability to pedal a tricycle or form sentences), and poor growth are concerning for fetal alcohol syndrome (FAS), the most severe of the fetal alcohol spectrum disorders. FAS includes a range of physical and neurocognitive findings caused by in utero alcohol exposure and is characterized by ≥2 of the following pathognomonic facial dysmorphisms:
As seen in this patient, midface hypoplasia, microcephaly, and poor growth are also common.
Neurocognitive effects are vast and include developmental delay, intellectual disability, memory issues, and poor adaptive functioning. Hyperactivity, inattention, and poor social skills (eg, decreased eye contact, disinterest in peer play) can also occur.
Women who are pregnant or trying to conceive are advised to abstain from alcohol completely because there is no known safe amount of prenatal alcohol consumption. Early diagnosis is critical so that affected children can maximize benefit from speech, physical, and occupational therapies.
(Choice A) DiGeorge syndrome (22q11.2 deletion) is associated with developmental delay and craniofacial abnormalities. In contrast to FAS, ocular hypertelorism and low-set, posteriorly rotated ears are typical in DiGeorge syndrome. In addition, this syndrome most commonly causes cyanotic congenital cardiac defects (eg, interrupted aortic arch), whereas this patient has features characteristic of the most common innocent pediatric murmur (ie, Still murmur).
(Choice C) In utero opioid exposure can lead to neonatal abstinence syndrome with symptoms ranging from irritability and poor sleep to failure to thrive and seizures. Dysmorphic facial features are not seen.
(Choice D) Fetal hydantoin syndrome caused by in utero phenytoin exposure can be associated with craniofacial anomalies (eg, midface hypoplasia), but its classic features, such as hypoplastic digits/nails, structural cardiac defects, and cleft lip/palate, are not seen in this patient. In addition, short palpebral fissures would not be expected.
(Choices E and F) Fragile X syndrome (FXS) and Down syndrome are common causes of intellectual disability and developmental delay. Stereotypical features of FXS include a long, narrow face and prominent ears, forehead, and chin, whereas patients with Down syndrome typically have upslanting palpebral fissures, epicanthal folds, and low-set, small ears.
Educational objective:
Fetal alcohol syndrome due to in utero alcohol exposure classically presents with the triad of small palpebral fissures, smooth philtrum, and thin vermilion border. Patients also have poor growth and associated neurodevelopmental issues (eg, development delay, intellectual disability, hyperactivity, poor social skills).