A 3-year-old boy is brought to the clinic due to increased seizure frequency. Over the past year, the patient has had recurrent tonic-clonic seizures that are poorly controlled despite multiple antiepileptic medications. The seizures have become more frequent in the past month and now occur daily. The patient has developmental delay and receives speech and physical therapy. He was born at term without perinatal complications and has received all age-appropriate vaccinations. Family history includes mild intellectual disability in his father. Physical examination is notable for multiple 1- to 2-cm hypopigmented macules on the trunk and lower extremities. MRI of the brain reveals subependymal nodules, as shown in the image below: Which of the following is associated with the most likely underlying condition in this patient?

Question

A 3-year-old boy is brought to the clinic due to increased seizure frequency.  Over the past year, the patient has had recurrent tonic-clonic seizures that are poorly controlled despite multiple antiepileptic medications.  The seizures have become more frequent in the past month and now occur daily.  The patient has developmental delay and receives speech and physical therapy.  He was born at term without perinatal complications and has received all age-appropriate vaccinations.  Family history includes mild intellectual disability in his father.  Physical examination is notable for multiple 1- to 2-cm hypopigmented macules on the trunk and lower extremities.  MRI of the brain reveals subependymal nodules, as shown in the image below:  Which of the following is associated with the most likely underlying condition in this patient?

Quizplus · Accepted Answer

11ec25c8_d5d4_c241_bc81_03771a1ce3a8_MD0003_00 This patient has refractory epilepsy, developmental delay, subependymal nodules, and hypopigmented macules, features suggestive of tuberous sclerosis complex (TSC). TSC is an autosomal dominant neurocutaneous disorder in which an inherited or de novo mutation in the TSC genes leads to benign tumors (hamartomas) of the brain, skin, and other organs. Seizures (eg, infantile spasms, tonic-clonic) are the most common presenting feature of TSC, with typical onset in infancy or early childhood. Intellectual disability and developmental delay are particularly prominent in patients with refractory epilepsy. Brain hamartomas, including cortical glioneuronal hamartomas (tubers) and subependymal nodules (red circles), are often present but do not correlate with the frequency or severity of seizure activity. Almost all patients with TSC also have characteristic skin lesions, including ash-leaf spots, as described in this patient with hypopigmented macules. Angiofibromas and shagreen patches (thickened skin with orange peel-like texture) are also common. subependymal nodules ash-leaf spots Angiofibromas Cardiac rhabdomyoma is highly associated with TSC, and all patients with suspected TSC should be evaluated with echocardiography. The tumor can be asymptomatic or cause a murmur, arrhythmia, or heart failure. Although often large in the newborn period, the mass typically regresses spontaneously after infancy. (Choice B) Optic nerve glioma is associated with neurofibromatosis type 1, an autosomal dominant neurocutaneous disorder that also causes seizures and intellectual disability. Skin findings include hyperpigmented café au lait macules, axillary freckling, and neurofibromas, none of which are present in this patient. In addition, subependymal nodules are not seen. neurofibromatosis type 1 (Choice C) Pheochromocytoma can occur with von Hippel-Lindau (VHL) syndrome and multiple endocrine neoplasia type 2 (MEN2), disorders associated with various benign and malignant tumors. Neither VHL syndrome nor MEN2 is associated with skin lesions. (Choice D) Bilateral vestibular schwannomas are pathognomonic of neurofibromatosis type 2, an autosomal dominant disorder that typically presents with hearing loss and tinnitus, not seizures, in young adults. Intracranial meningiomas and cutaneous plaques can occur, but subependymal nodules and hypopigmented macules are not associated findings. (Choice E) Wilms tumor (nephroblastoma) is associated with WAGR and Beckwith-Wiedemann syndromes. WAGR is characterized by Wilms tumor, Aniridia, Genitourinary abnormalities, and intellectual disability (mental Retardation). Beckwith-Wiedemann syndrome typically presents with macrosomia, macroglossia, and hemihypertrophy. Neither causes seizures or skin findings. Educational objective: Tuberous sclerosis complex should be suspected in a patient with refractory epilepsy, developmental delay, intellectual disability, and characteristic skin findings (eg, ash-leaf spots). Associated tumors include subependymal nodules and cardiac rhabdomyomas. References: Incidence of tuberous sclerosis and age at first diagnosis: new data and emerging trends from a national, prospective surveillance study. (http://www.ncbi.nlm.nih.gov/pubmed/30016967) Diagnosis and treatment of tuberous sclerosis manifestations in children: a multicenter study. (http://www.ncbi.nlm.nih.gov/pubmed/29558773)

A 3-Year-Old Boy Is Brought to the Clinic Due to Increased