What is Usher Syndrome?

Patient Presentation
A 2-year-old female came to clinic with a 2 day history of upper respiratory infection symptoms, pulling on her ears, and being cranky. She had a temperature of 38.8°C maximum that improved with acetaminophen. The past medical history revealed 4 previous otitis media infections with the last one being 6 months ago. The pertinent physical exam showed a cranky appearing female with a temperature of 38.2°C, respiratory rate of 24 and growth parameters that were 50%. HEENT showed copious clear rhinorrhea and bilateral tympanic membranes that were red and bulging with yellow purulent material behind the tympanic membrane. There was no membrane movement in either ears.

The diagnosis of bilateral acute suppurative otitis media was made. The mother said that she was glad to know what the problem was but was very anxious because this was her 5th ear infection and she wanted a referral to an otolaryngologist. “I don’t really want her to have surgery for her ears, but my cousin’s baby was born deaf and he’s just been diagnosed with something called Usher. I looked it up on the Internet and it’s really bad. They can have eye problems too. I’m really worried about her hearing and think I would feel better if I knew she wasn’t going to have hearing problems,” she explained. “I’m very sorry to hear about your cousin’s child. I don’t remember exactly what Usher is, but will try to find out. Your daughter’s newborn hearing test should have been normal otherwise we would have sent her to the ear doctor already but I’ll check to make sure. Have you ever thought that she was having problems hearing, either now or before?” the pediatrician inquired. “I think her test when she was born was normal and I’ve never been worried, but she’s had these infections and now this baby who is deaf. I’m just very worried,” she replied. “We’ll I can understand that. It is not unreasonable to have her hearing tested after having 5 ear infections, but her last one was a while ago and for most children the ear infections stop as they get older and there are usually no problems with long-term hearing loss. I’ll order a hearing test for her after this ear infection is over. In the meantime, I’ll try to find out more about Usher, ” she offered. “I think I will feel a lot better after I know that her hearing is normal,” the mother said.

Discussion
Over 7000 diseases are considered rare disorders according to the National Organization for Rare Disorders® (NORD, rarediseases.org). NORD is a patient advocacy organization dedicated to individuals with rare diseases and the organizations that serve them. They have information on about 1200 rare diseases on their website (https://rarediseases.org/for-patients-and-families/information-resources/rare-disease-information/).

Hearing loss (HL) is not rare and is a common problem across the ages. It affects 360 million people worldwide which is about 5% of the population. There are many causes of hearing loss and a differential diagnosis can be reviewed here. HL can be classified as congenital vs acquired, with congenital being further classified according to the genetic inheritance (e.g. recessive, dominant, sex-chromosome), onset, severity and whether it is associated with syndromes or not.

Retinitis pigmentosa (RP) is a group of retinal degenerative diseases that have loss of photoreceptors and retinal pigment deposits. Non-syndromic RP causes visual deficits over several decades. Initial symptoms are night blindness and later patchy peripheral vision losses that evolves into scotoma, tunnel vision and blindness. There are many syndromes which have RP as part of their symptoms with Usher syndrome (14% of all RP cases) and Bardet Biedel syndrome as two of the most common ones.

Learning Point
Usher syndrome (US) was described as early as 1858, but it is named for British ophthalmologist Charles Usher who noted the genetic inheritance.
US has later onset RP and congenital, bilateral, neurosensory hearing loss.
Of the syndromes known to affect both hearing and vision, “…about half of the affected cases are caused by mutations attributed to Usher syndrome.”
US is autosomal recessive with an estimated prevalence of 3-10/100,000 people. There are multiple genes involved (chromosomes 1, 3, 10, 11, 14, 21).
There are 3 major types and a possible 4th.

  • Type I – 70-75% of patients – has congenital severe to profound hearing loss, congenital vestibular dysfunction, RP begins in usually < 10 years
  • Type II – 26% of patients – has congenital moderate to severe hearing loss (quite “hard of hearing”), no vestibular dysfunction, RP is diagnosed ages 10-40 years
  • Type III – 4% of patients – has variable progression hearing loss that starts in years 20-30, variable vestibular dysfunction, RP starts in 20s.
    It is least common, but more common in some populations including Ashkenazi Jewish and Finnish populations.

  • Type IV – its existence is being debated by researchers and may be X-linked recessive

Treatment is directed by ophthalmologists and otolaryngologists who along with audiologists, speech and language pathologists and other professionals may help patients with different therapies. Some patients take Vitamin A as part of their treatment.

Questions for Further Discussion
1. How good are vision and hearing screening tests? A review can be found here https://pediatriceducation.org/2011/11/14/how-good-are-hearing-and-vision-screening-tests-in-children-2/
2. What are indications for referral to a geneticist?
3. What are indications for cochlear implants?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for this topic: Usher Syndrome

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Usher Syndrome. National Organization for Rare Diseases. Available from the Internet at https://rarediseases.org/rare-diseases/usher-syndrome/ (cited 9/7/17).

Hamel C. Retinitis pigmentosa. Orphanet J Rare Dis. 2006 Oct 11;1:40.

Koffler T, Ushakov K, Avraham KB. Genetics of Hearing Loss: Syndromic. Otolaryngol Clin North Am. 2015 Dec;48(6):1041-61.

Usher Syndrome, Type i; USH1 #276900. Online Mendelian Inheritance in Man.
Available from the Internet at Koffler T, Ushakov K, Avraham KB. (rev. 3/8/16, cited 9/6/17).

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa

What Are the Health Needs of Incarcerated Youth?

Patient Presentation
A 15-year-old male came to clinic for his health supervision visit. He was doing well and there were no concerns. His mother had a red mark on her cheek that the pediatrician noticed and asked about. The mother and son both started to grin somewhat. “We’ll I was the innocent bystander in a fight between two teenagers at the juvenile detention center I teach at. They started to go at it and when the probation officers came in to break it up, I got caught off balance trying to move away and tripped over a desk and hit the edge. I didn’t actually get hit but it looks like I was. Actually it could have happened in any high school, its just seems worse because I work at the ‘juvie jail,'” she explained. She went on, “I really like working there because the kids have so many needs. Their stories can be really, really sad and we see lots of mental health, physical and social issues. The classroom at least is a consistent place for all of them.” Later, the pediatrician looked up what are some of the health care needs of incarcerated youth.

Discussion
In the US during 2011, ~60,000 youth were incarcerated at some time in a correctional facility. Boys are detained more than girls (86% vs 14% respectively in the US, 95% male in the United Kingdom in 2014) but girls have more health issues. There are racial and ethnic differences with 38-40% of detainees being black, 23% being Hispanic/Latino and 32% being white, and 5% other. For detained youth, 5% are for violent crimes, 22% for non-violent property crimes and the majority of the rest are for non-violent offices such as substance use. The average length of detainment is 3-4 months and unfortunately the rates of recidivism are higher for youth than for adults; for youth, 75% are rearrested within 3 years. Detained youth have a higher risk of mortality at 4x the general population; girls have an 8x higher rate.

A comprehensive view of their health care needs to be provided to the youth, upon their arrival, during detention, transitioning out of and after detention. For formerly detained youth, primary care physicians can help with continuing primary care including immunizations and screenings for sexual and mental health issues, determining if consultative care is needed and referring as necessary for pediatric specialty care, mental health or substance abuse treatment, working with local school districts to assist with educational/academic needs, working with social services to help with overall family needs, and providing information to the probation officers and other legal system representativse as appropriate.

Within the detention system, girls are less common and therefore represent a special population. LGBTQ (Lesbian, Gay, Bisexual, transgender or questioning) youth were 15% of the detained population (11% for boys, and 27% for girls). Youth involved in sex-trafficking are also viewed as a special population.

Learning Point
Many health problems are seen at higher rates in detained youth. The priority primary health needs include dental, infectious illness, reproductive health needs and trauma-related injuries. In the United Kingdom the most common physical health needs were: vision (13%), oral health (12%), skin problems (12%), asthma (11%), weight problems (11%) and genito-urinary problems (10%). In the United Kingdom mental health prevalence rates showed personality disorder (~84%), drug dependency (~57%), depression (~50%), neuroses (52%) and psychosis (8%).

Health problems of detained youth include:

  • Mental – 66% of boys and 75% of girls have at least 1 mental health need, many are undiagnosed
    • Behavior
    • Conduct disorder
    • Post traumatic stress disorder
    • Mood disorders including anxiety and depression and suicidality
      • Suicidality is very common with 52% of youth reporting recent suicidality and 1/3 with an attempt.
    • Neurodevelopment
      • Attention/ADHD
      • Learning disabilities including specific learning disabilities such as dyslexia
    • Substance use and abuse – alcohol and marijuana use are especially high among detained youth (74 and 84% respectively). Girls are more likely to use other substances.
      • Alcohol
      • Cocaine or crack
      • Crystal methamphetamine
      • Ecstasy
      • Marijuana or hashish
  • Physical
    • Acute self-limited illness, e.g. upper respiratory infections, dermatological problems
    • Chronic problems
      • Asthma
      • Diabetes
      • Seizures
      • Sickle cell disease
    • Dental
      • Dental decay
      • Abscess of the jaw
      • Gum disease
    • Pain – females tend to report more musculoskeletal pain
      • Abdominal pain
      • Backache
      • Headache
    • Sexual – detained youth have higher rates of sexual activity and lower rates of contraception
      • Sexually transmitted infections
        • Chlamydia, gonorrhea, HIV and Hepatitis C, syphilis
      • Pregnancy
        • “…1 in 5 detained youth either [are] having a child or expecting a child.” Fourteen percent of boys and 9% of girls already have a child.
    • Trauma-related injury
    • Vision
  • Other
    • Under education
    • Under immunization

    Questions for Further Discussion
    1. What training have you had about detained youth?
    2. How are the health needs of detained youth addressed in your clinical location?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Child Behavior Disorder

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Perry RC, Morris RE. Health care for youth involved with the correctional system. Prim Care. 2014 Sep;41(3):691-705.

    Lennox C. The health needs of young people in prison. Br Med Bull. 2014 Dec;112(1):17-25.

    Barnert ES, Perry R, Morris RE. Juvenile Incarceration and Health. Acad Pediatr. 2016 Mar;16(2):99-109.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa

  • How Common Is Hereditary Angioedema?

    Patient Presentation
    An 8-year-old female came to clinic because of swelling in her right lower extremity x 1 day. She had noticed the problem the night before but didn’t tell her parents until that morning. She had some general discomfort and pruritus with moving her leg but denied any fever, limp or problems walking. She denied any problems breathing or swallowing. She had been playing outside the day before. The past medical history was positive for large local reactions to insect bites. The family history was negative for kidney problems, thromboses, or swelling of body parts. There was a family history of seasonal allergies but no specific asthma, food allergies or angioedema. The review of systems was negative.

    The pertinent physical exam showed normal vital signs including temperature and growth parameters in the 75-95%. HEENT, lung and abdominal examinations were normal. Her extremities showed several bug bites with excoriations on both lower legs that also had some enlargement around the bug bites, but the right side was slightly larger than the left.

    The diagnosis of bilateral lower leg swelling secondary to enlarged local reactions to bug bites was made. The family was educated about large local reactions and given the proper dosing for diphenhydramine to use for the pruritus. After seeing the patient, the attending discussed the differential diagnosis of edema with the medical student. She noted that if an allergic reaction was being considered, questions about problems such as difficulty swallowing or breathing should be asked, and the oropharynx and lungs inspected and ausculated. “It’s possible that the patient is having angioedema and doesn’t realize it,” said the attending. “I know you can have acute angioedema but isn’t there a genetic form too? How common is the genetic form?” he asked. “There is a genetic form called hereditary angioedema. It’s not very common, and I’d have to look that up,” the attending replied.

    Discussion
    Angioedema is edema that is non-pitting, self-limited occurring in non-dependent areas usually in an asymmetric distribution usually on the lips, face, hands, feet, genitals and also in the bowel. It usually develops over minutes to hours (often 1-2 hours) with resolution usually within 24-48 hours. Angioedema often occurs with urticaria but 20% of patients may have isolated angioedema. Acute allergic angioedema is often caused by drugs (including antibiotics and non-steroidal anti-inflammatory drugs), foods, infections, insects, various organic substances (i.e. latex, preservatives, formaldehyde, etc.), and other allergens such as animal danders, dust mites, pollens and molds. Common triggers in children are infections including the viruses Coxsackie A, Epstein-Barr virus, Hepatitis B, and Herpes simplex. Bacterial causes include otitis media, pharyngitis, sinusitis and urinary tract infections. Parasitic infections causing angioedema include filariasis, strongyloides and toxocara. Physical factors can cause mast cell release causing angioedema. These include exposure to cold, heat, pressure, the sun and vibration.

    Hereditary angioedema (HAE) is a rare genetic disorder. HAE is caused by decreased amount of C1 inhibitor (Type 1, 85% of cases), normal amount of C1 inhibitor but decreased functionality (Type II, 15%) and normal C1 inhibitor and functionality but with angioedema. Type I and Type II HAE are autosomal dominant diseases but up to 25% may have a de novo mutation. There is near complete penetrance. Most patients are heterozygous. C1 inhibitor is a serine protease inhibitor. As the C1 inhibitor is not able to regulate various enzymatic processes, bradykinin is released which causes increased vascular permeability and vasodilation.

    Type I and Type II HAE clinical phenotypes are the same. Patients may have symptoms from childhood but have worsening around puberty and adolescence. Some are not diagnosed usually until adolescence to young adulthood. The average diagnosis delay is 11-20 years because of non-recognition of symptoms, misdiagnosis and patients lacking a family history. Patients have subcutaneous and submucosal edema that is non-pruritic and not associated with urticaria. Patients with HAE do not respond to antihistamines, epinephrine and corticosteroids. Initial presentation can be a fatal laryngeal attack. Swelling progresses over hours (peak around 24 hours) and subsides over days (2-5 days) Subcutaneous and submucosal swelling especially of peripheral extremities and the abdomen is the most common but orolaryngeal or genital edema also occurs. Single or multiples areas can be affected and affected sites may be non-contiguous. Cutaneous swollen areas are noticeable, asymmetric, and non-pitting – which can cause disfigurement and functional problems during the attacks. Abdominal attacks may cause pain (generalized or colicky), nausea, and emesis and may mimic surgical causes of abdominal pain. Facial and laryngeal edema are less common but can occur and patients are at an increased risk of asphyxiation. As noted initial presentation can be a fatal laryngeal attack. The genitalia can also be involved. A prodrome may or may not occur including erythema marginatum (i.e. non-pruritic, serpigenous rash), local discomfort, tingling, weakness, and fatigue.

    Severity and frequency of attacks vary within and among individuals even in the same family. Without treatment, average frequency is 7-14 days but can occur every 3 days to never again. Each attack may be similar or different. The exact initiating mechanism(s) is unknown but stress (including mental stress, fatigue), trauma, infection, and increased estrogen states can be triggers. Exogenous estrogen as a form of family planning is not recommended and other forms should be used instead. Dental manipulation may cause a laryngeal or oral attack.

    Diagnosis is by protein level and functional assay. It is usually made after 1 year of age because C1 inhibitor levels are low before then. Gene sequencing is also available. As this is autosomal dominant, first-degree relatives should be screened along with appropriate second-degree relatives. Treatments are available and are highly effective. Berinert® is an on demand treatment for children and adolescent that was approved in July 2016. It works as a human C1 esterase inhibitor. Other on demand treatment for adolescents and adults include a kallikrein inhibitor, bradykinin receptor antagonist and recombinant human C1 inhibitor. Short- and long-term prophylactic treatments are also available. In addition to drug treatment, a comprehensive management plan needs to be developed and re-visited frequently. This includes specialty care from an HAE specialist, understanding signs and symptoms of the disease, when to treat and potentially re-treat, where to treat (i.e. home or medical facility), and how to access medical facilities and specialty care among other elements of the plan.

    HAE with normal C1 inhibitor was identified in 2000. It appears to be less common and more complex. Testing for some mutations is positive (F12). Patients still have a family history and clinical history of angioedema which indicates this disease.

    Learning Point
    In the United States the exact prevalence is unknown but estimated at a range of 1:10,000 to 1:100,000 persons and appears to affect all ethnic groups equally.

    Questions for Further Discussion
    1. How is acute angioedema treated?
    2. What are physical urticarias and how are they treated?
    3. How is lymphedema different than angioedema?

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for these topics: Vascular Diseases and Insect Bites and Stings.

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Kuhlen JL, Banerji A. Hereditary angioedema: special consideration in children, women of childbearing age, and the elderly. Allergy Asthma Proc. 2015 Nov-Dec;36(6):425-32.

    Zuraw BL, Christiansen SC. How we manage persons with hereditary angioedema. Br J Haematol. 2016 Jun;173(6):831-43.

    Frank MM, Zuraw B, Banerji A, Bernstein JA, Craig T, Busse P, Christiansen S, Davis-Lorton M, Li HH, Lumry WR, Riedl M; US Hereditary Angioedema Association Medical Advisory Board.
    Management of Children With Hereditary Angioedema Due to C1 Inhibitor Deficiency. Pediatrics. 2016 Nov;138(5).

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa

    What Clinical Signs Can Be Associated With Benign External Hydrocephalus?

    Patient Presentation
    A 6-month-old female was seen by a pediatrician for macrocephaly. The parents had normal head circumferences. The head circumference velocity had been increasing so a head magnetic resonance imaging study was completed and was normal. The infant was acting normal and did not have any developmental delays reported other than having more problems getting into a sitting position or staying there if placed because of balance with her head. The parents said the infant was without illness and was not taking any medications or supplements in addition to her normal breastfeeding and oatmeal cereal. The family history was negative for any neurological, developmental or growth problems.

    The pertinent physical exam showed a smiley infant with weight in the 50%, length in the 75% and a head circumference > 95% and growing at 2 cm/month growth velocity. The vital signs were normal including a normal temperature. The anterior fontanele was open, bulging when palpated in a seated position without pulsations and was ballottable. Her neurological examination was normal.

    The diagnosis of macrocephaly in a healthy appearing infant with normal imaging but with a bulging fontanele was made. The pediatrician was concerned about the bulging fontanele and asked a colleague about the follow-up that might be recommended. He was reassured when the other pediatrician felt that as the child did not appear ill that a spinal tap for meningoencephalitis was not indicated at this time. “I think that because there is increased pressure the fontanele is going to be bulging as this is the pop-off valve for the fluid. You could just talk with neurosurgery but usually if the child isn’t having any problems they are certainly not going to do any procedures. You could monitor the child closer with the parent doing weekly head circumferences and sending those to you and in that way you have close follow up and can also talk with the parent about the baby’s development too,” the colleague offered. The pediatrician talked with the colleague the next week and said that neurosurgeon had agreed that close follow-up would be good to make sure there weren’t developing problems but that they would not do any procedures at this time.

    Discussion
    Hydrocephalus is an abnormal accumulation of cerebrospinal fluid (CSF) in the ventricles and/or subarachnoid spaces. External hydrocephalus is a communicating hydrocephalus often defined as the patient having a rapidly enlarging head circumference (HC) and enlargement of the subarachnoid spaces especially over the frontal lobes with normal or moderately enlarged ventricles. Benign external hydrocephalus (BEH) is a self-limited external hydrocephalus that occurs during infancy and resolves spontaneously in childhood, usually by age 2 years, that is felt to not cause significant problems. It was first described by W.E. Dandy 1947 and there have been other terms used to describe this entity that indicate further understanding of the entity and the presumed pathophysiology.

    A recent study in Norway reported the incidence to be 0.4 per 1000 live births. Some patients seem to have a genetic propensity to BEH.

    The cause of BEH is debated but is most commonly felt to be because of immature arachnoid villi. Arachnoid granulations become visible between 6-18 months and then gradually develop in size over years. It is felt that there is a delay in maturation of this process where the villi are not able to reabsorb the CSF that is being produced, thus the CSF accumulates externally in the subarachnoid spaces.

    An evaluation for macrocephaly is a common reason a child has neuroimaging which can include transfontanele ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI). Cerebral atrophy and subdural fluid collections should be differentiated from external hydrocephalus. The “cortical vein sign” where cortical veins are visualized within fluid collections in the cerebral convexities suggests that the fluid is not caused by subdural fluid collections that would compress the subarachnoid space and the veins within it. Intracranial pressure measurements show normal to slightly elevated pressures (6-16 mm Hg) and the fluid analysis has been reported as normal or with slight xanthochromia or slight elevated protein.

    BEH is usually felt to have a “benign” prognosis but there can be problems. External hydrocephalus has an increased risk of subdural hematomas after minimal or no head trauma. Developmental delays, especially motor delays, are often seen for some time in infancy and toddlerhood. There are few long-term studies and those generally find that children overall seem to do well, but there can be some subtle changes. A recently study of at least 7 years follow-up of children with BEH showed subtle long-term neurocognitive problems. This was true for both children who received shunting or were treated conservatively. The authors acknowledge that there may be a selection bias as the group came from a neurosurgery population. The authors found even in non-operated children, children performed significantly poorer in attention span, psychomotor speed and executive functioning. BEH treatment is usually conservative with observation of the condition, or use of acetazolamide. Intervention with needle aspiration or shunting procedures is usually for patients with clinical signs and symptoms of increased intracranial pressure.

    The differential diagnosis of a bulging anterior fontanele can be found here.

    Learning Point
    According to a comprehensive literature review, the clinical signs and symptoms of BEH include:

    “The large or enlarging head appear indistinguishable from those seen in other hydrocephalus cases (…). A relatively common sign is a tense anterior fontanel (…). Other early symptoms and signs have also been reported occasionally: dilated scalp veins (…), frontal bossing (an unusually prominent forehead) (…), irritability (…), hypotonia (…), vomiting (…), gross motor delay (…), ataxia (…), poor head control (…), seizures (…), fever (…), and mental retardation (…). We have not found any articles reporting sunset gaze.”

    Questions for Further Discussion
    1. What are indications for ventriculoperitoneal or similar neurological shunt placements?
    2. What causes macrocephaly?
    3. When should the anterior fontanele close? Learn more here.

    Related Cases

    To Learn More
    To view pediatric review articles on this topic from the past year check PubMed.

    Evidence-based medicine information on this topic can be found at SearchingPediatrics.com, the National Guideline Clearinghouse and the Cochrane Database of Systematic Reviews.

    Information prescriptions for patients can be found at MedlinePlus for this topic: Hydrocephalus

    To view current news articles on this topic check Google News.

    To view images related to this topic check Google Images.

    To view videos related to this topic check YouTube Videos.

    Zahl SM, Egge A, Helseth E, Wester K.
    Benign external hydrocephalus: a review, with emphasis on management. Neurosurg Rev. 2011 Oct;34(4):417-32.

    Marino MA, Morabito R, Vinci S, et.al. Benign external hydrocephalus in infants. A single centre experience and literature review. Neuroradiol J. 2014 Apr;27(2):245-50.

    Mikkelsen R, Rodevand LN, Wiig US, et.al. Neurocognitive and psychosocial function in children with benign external hydrocephalus (BEH)-a long-term follow-up study. Childs Nerv Syst. 2017 Jan;33(1):91-99.

    Wiig US, Zahl SM, Egge A, Helseth E, Wester K. Epidemiology of Benign External Hydrocephalus in Norway-A Population-Based Study. Pediatr Neurol. 2017 Aug;73:36-41.

    Author
    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa

    Date
    October 2, 2017