Pediatric Genetic Diseases Flashcards
What is Neurofibromatosis type 1? AKA? Diagnosis? Inheritance?
neurofibromatosis type 1 (NF1). NF1 is also known as von Recklinghausen disease and is an autosomal-dominant condition with near-complete penetrance. The condition can occasionally be due to a spontaneous mutation. The disease is caused by a genetic defect on a tumor suppressor gene of chromosome 17, which codes for neurofibromin. The condition affects the skin, nervous system, eyes, bone, and soft tissue. The diagnostic criteria include 2 or more of the following:
- 6 or more café-au-lait macules greater than 5 mm in prepubertal individuals or greater than 15 mm postpubertal individuals
- 2 or more lisch nodules (iris hamartomas)
- Sphenoid dysplasia
- 2 or more neurofibromas
- Freckling in axillary or inguinal region (also known as Crowe sign)
- Optic glioma
- First-degree relative with the condition
The patient has more than 6 café-au-lait macules greater than 5 mm, lisch nodules on examination, and positive Crowe sign. This patient’s father also likely has NF1. This gives more than 2 diagnostic criteria for NF1.
What is neurofibromatosis type 2? Inheritance?
Neurofibromatosis type 2 is an autosomal-dominant condition. Patients present with bilateral acoustic neuromas, which are schwannomas of the eighth cranial nerve. It is associated with chromosome 22 and codes for merlin. These patients have fewer café-au-lait macules and do not form lisch nodules.
What is Sturge-Weber syndrome? Inheritance?
Sturge-Weber syndrome is a non-inherited congenital condition. Patients present with a congenital port wine stain in the distribution of the V1 and V2 trigeminal nerve. The condition is associated with epilepsy, eye abnormalities including glaucoma, intellectual disability, and hemiatrophy. The port wine stain is a pink to red patch overlying the forehead and eyelids and is most commonly unilateral.
What is Tuberous Sclerosis? Inheritance?
Tuberous sclerosis is an autosomal-dominant disorder that is caused by mutations in hamartin and tuberin. Patients present with seizures secondary to cortical tuber, intellectual disability, ash leaf spots (hypomelanotic patches), shagreen patch, and adenoma sebaceum (facial angiofibroma). It is also associated with epilepsy, intellectual disability, and autism.
What is Von-Hippel-Lindau Syndrome? inheritance?
von Hippel-Lindau syndrome is an autosomal-dominant condition associated with clear cell renal cell carcinoma, pheochromocytomas, and hemangioblastomas. Hemangioblastomas are well-circumscribed, capillary vessel-rich benign neoplasms affecting 60-84% of patients with von Hippel-Lindau syndrome.
Clinical hallmarks of VHL disease include the development of retinal and central nervous system (CNS) hemangioblastomas (blood vessel tumors), pheochromocytomas, multiple cysts in the pancreas and kidneys, and an increased risk for malignant transformation of renal cysts into renal cell carcinoma. The wide age range and pleiotropic manner in which VHL disease presents complicates diagnosis and treatment in affected individuals, as well as their at-risk relatives. Other signs and symptoms associated with VHL disease include headaches, problems with balance and walking (due to involvement in the cerebellum with an hemangioblastoma), dizziness, weakness of the limbs, vision problems, and high blood pressure. The presence of a negative Romberg test with ataxia in this patient is indicative of the possible presence of a cerebellar hemangioblastoma.
What is McCune-Albright Syndrome?
McCune-Albright syndrome is a rare form of gonadotropin-independent precocious puberty caused by a somatic mutation in the activating subunit of the G-coupled protein receptor responsible for follicle-stimulating hormone/luteinizing hormone signaling, leading to constitutive activation. This syndrome is characterized by a triad of precocious puberty, fibrous skeletal dysplasia, and café-au-lait spots. Enlarged bilateral ovaries are often seen on ultrasound. Clinically, cyclic vaginal bleeding precedes breast development. Accelerated bone growth and advanced bone maturation left untreated will compromise achievement of adult height.
What is Turner syndrome?
Ullrich-Turner syndrome is associated with high arched palate and increased carrying angle of the arm. More classic signs include a webbed neck (cystic hygroma), broad “shield” chest, and streak ovaries. Turner syndrome is also associated with coarctation of the aorta. Turner syndrome is a genetic disorder only affecting females and is characterized by the 45, XO genotype, with an incidence of 1:10,000. A karyotype is diagnostic. Workup should include a baseline echocardiogram, renal ultrasound, blood pressure, and hearing screen. The prognosis is good and patients can expect a normal lifespan; however, these patients are infertile.
Klinefelter’s syndrome fertility strategy?
Historically, patients with Klinefelter’s syndrome were considered infertile; however, artificial reproductive technologies have allowed nearly 50% of affected males to sire their own offspring. A two-step process of microsurgical TESE and subsequent ICSI is often used in this situation. Successful fertilization rates vary by study but often are near 50%. A candidate with an age > 34 years old may predict decreased sperm retrieval, but this is not certain and harvested testicular tissue may occur during adolescence or adulthood.
