Challenging Case: A Multidisciplinary Approach to Demystifying Chronic Sleep Impairment in an Infant with a Complex Medical and Behavioral Profile.

CASE: X is a 22-month-old White male infant with a complex medical history, including diagnoses of FBXO11 mutation, hypotonia, restrictive lung disease and mild intermittent asthma, laryngotracheomalacia, obstructive sleep apnea (OSA), feeding difficulties with a history of aspiration, gastroesophageal reflux disease (GERD), and developmental delays. X's medical presentation has resulted in multiple prior medical admissions for respiratory failure due to acute illnesses, procedures and treatments including gastrojejunostomy (GJ) tube dependence, supraglottoplasty to reshape tissues of the upper larynx, and the use of biphasic positive airway pressure (BiPAP) at night and room air during the day when he is at baseline. In addition, he has nocturnal events characterized by significant agitation, screaming, crying, body stiffening and limb movements with pauses in breathing, mouth breathing, restless sleep, and difficulty waking in the morning with concomitant daytime fatigue despite above treatments for OSA. There is no history of congenital heart disease or sudden unexplained death. Family history is noncontributory because parents are negative for the FBXO11 variant.X's sleep disruption has led to significant sleep deficits for both X and his caregivers, who spend much of the night strategizing on how to console him. X has undergone several sleep studies, starting when X was aged 4 months, at several children's hospitals across the nation to determine the cause of his chronic sleep disturbance, which yielded limited information and treatment success. As an infant, X received a medical workup and was subsequently treated with a proton pump inhibitor (PPI) for reflux. At 12 months, he was diagnosed with disordered sleep with myoclonic jerks and started on melatonin and gabapentin for involuntary movements. At 13 months, gabapentin was weaned back because of intolerance, and at 15 months, nortriptyline and clonidine were started because of worsening symptoms to target potential neuropathic pain. While most of his symptoms were at night, he had occasional daytime screaming episodes, particularly when experiencing illness. Gabapentin and clonidine were stopped because nortriptyline seemed most effective.At 17 months, the results from a sleep study led to a diagnosis of night terrors, and several clinicians agreed that X's sleep disruption was behavioral in nature. At this time, an infant mental health consultant met with a sleep psychologist on the family's behalf to support family in considering systematic desensitization therapy to increase tolerance to wearing his BiPAP mask, as well as other behavioral and sleep hygiene strategies, which were tried on several occasions and again, resulted in limited improvement in functioning.At 19 months, X's multidisciplinary team reconsidered a night terror diagnosis after a failed trial of clonazepam and pursued a differential diagnosis of periodic limb movement disorder (PLMD). X trialed gabapentin again, but this time only a nighttime dose, per sleep medicine and psychiatry recommendation. While this brought some temporary relief from nighttime distress, despite increasing to the highest dose for age and weight (15 mg/kg/dose), this became less effective, and he was weaned off at 22 months. He had been on iron supplementation since age 6 months and received an iron infusion at 22 months because of persistently low ferritin levels and PLMD in sleep.At 24 months, X was briefly trialed on levetiracetam. While no evidence for seizures on EEG was present, this medication was chosen for involuntary movements and genetic risk for seizures. However, this medication was not useful. At 25 months, an evaluation with a movement disorder physiatrist resulted in a diagnosis of nocturnal paroxysmal dystonia, and he was started on baclofen, which has provided some, but not complete relief to nighttime symptoms. Parents are reporting he has more "good nights" than "bad nights," but "bad nights" come in stretches of a few days in length with no known trigger or relief.Most recently, X was evaluated by general genetics. Whole exome sequencing (WES) was pursued which revealed a pathogenic de novo variant in FBXO11 and provides a likely cause for his neurodevelopmental phenotype. However, he has some features not explained by FBX011; thus, reanalysis of his WES was performed and revealed a de novo variant of uncertain significance in RAF1. Because pathogenic variants in RAF1 have been associated with dilated cardiomyopathy and Noonan spectrum disorder, it was recommended that X be followed periodically in a cardiac genetics clinic. Family is well connected into the FBXO11 community, including supportive Facebook groups. Parents have shared that they do not feel X's breathing issues and pain fit with the phenotype of other children with FBXO11 mutations.X is also enrolled in a medical child care program to facilitate development and social-emotional functioning and receives learning, speech, occupational, physical, and feeding therapy while in attendance. Despite periods of absence due to contracting numerous viral illnesses over the past several months, X continues to make progress across developmental therapies and happily engages when at the program.What additional diagnostic tests and treatment should be considered to better understand X's medical and behavioral presentation? What are the implications of chronic sleep deprivation and stress on the behavior and development of infant with X's profile? What are important psychosocial considerations because it relates to children with medical complexity (CMC), particularly for X and his family to support caregiver, family, and X's quality of life and overall well-being?

Social Determinants of Health and the Role of Routine Pediatric Care in a Medically Complex Toddler.

CASE: Late on a Friday afternoon, a new family presents to your practice for urgent care. They come with their youngest child Mai, a 2-year-old girl, who, although born in the United States at 36 weeks gestation, has resided in Laos with her grandparents for the past 16 months. Your triage nurse tells you that she has a fever and was found to have profound anemia while at the WIC (Special Supplemental Nutrition Program for Women, Infants, and Children) office earlier today.On walking into the room, you describe Mai as "listless" and "sickly." Her vitals were notable for fever (102°F), tachycardia (140 beats per minute), and tachypnea (35 breaths per minute). On physical examination, she was grunting with a systolic ejection murmur and without hepatosplenomegaly. Laboratory test results revealed hemoglobin of 2.2 g/dL, hematocrit of 12%, mean corpuscular volume of 50 fL, red cell distribution width of 27%, reticulocyte count of 3%, ferritin of <2 ng/mL, iron of 15 µg/dL, total iron binding count of 420 µg/dL, white blood cell count of 13.5 K/µL, and platelets of 605 K/µL. Her evaluation was consistent with severe iron deficiency anemia (IDA), which was further supported by reported restrictive diet and excessive cow milk intake of 35 ounces daily. She was admitted to the Pediatric Intensive Care Unit in high-output cardiac failure and was slowly transfused with 15 mL/kg of packed red blood cells over 2 days with careful monitoring. Once stabilized, she was transferred to the inpatient floor for further nutritional evaluation and supplementation. Additional workup, including hemoglobin electrophoresis, fecal occult blood test, celiac studies, and stool parasite testing were normal. The clinical picture was consistent with a viral infection in the setting of profound IDA and malnutrition.Although her clinical status had improved, she remained inpatient for nutritional optimization. Her height was at the 54th percentile (z-score: 0.11), weight was at the first percentile (z-score: -2.25), and body mass index was below the first percentile (z-score: -3.18), diagnostic of severe protein-calorie malnutrition. She was evaluated by an interdisciplinary growth and nutrition team, received multivitamin and mineral supplements, and was monitored for refeeding syndrome. She was noted to be "difficult to engage," "resistant to new faces," and made little progress on expanding her dietary choices. Concerns about a possible diagnosis of autism spectrum disorder were raised by her treating team. What would you do next? REFERENCE: 1. Bouma S. Diagnosing pediatric malnutrition: paradigm shifts of etiology-related definitions and appraisal of the indicators. Nutr Clin Pract. 2017;32:52-67.

Transitions, Suicidality, and Underappreciated Autism Spectrum Disorder in a High School Student.

CASE: Alex is a 14-year-old Portuguese-American boy with a psychiatric history starting at age 5 who presents to your primary care practice after an insurance change.He was delivered prematurely at 32 weeks and diagnosed with congenital hypothyroidism at the age of 6 weeks and growth hormone deficiency at the age of 2 years; he is in active treatment for both. He otherwise met developmental milestones on time yet continues to have significant fatigue despite adequate sleep and vitamin D supplementation.His family history is remarkable for maternal anxiety, depression, suicidal thoughts, and previous attempted suicide, as well as anxiety, alcoholism, depression, and attention-deficit/hyperactivity disorder (ADHD) in the extended family.Alex has had multiple psychiatric diagnoses by sequential providers. He was diagnosed with generalized anxiety disorder and ADHD by 5 years of age, major depressive disorder by 11 years of age, persistent depressive disorder by 12 years of age, and ultimately disruptive mood dysregulation disorder because of severe and persistent temper outbursts associated with negative mood and behavioral dysregulation, leading to recurrent crisis evaluations. He has been psychiatrically hospitalized twice, in the fifth and seventh grade, for suicidal ideation (SI) and elopement from home, respectively. He recently completed a 2-week acute residential placement, during which no medication changes were made. Current medications include escitalopram 20 mg daily, guanfacine 1 mg 3 times daily, sustained release bupropion 100 mg twice daily, levothyroxine, vitamin D, and a weekly somatropin injection. He has not been able to tolerate psychostimulants or nonstimulant agents because of treatment-emergent SI.Now in the ninth grade, he continues to be easily distracted by peers, with impulsive behaviors and reduced self-regulation. Despite receiving special education services since the fifth grade, his academic performance has been poor, and he has limited motivation. Previous testing indicated average in an intelligence quotient test, with relative deficits in working memory compared with above average strength in fluid reasoning. He dislikes school and has few friends. He has always been noted to be "immature." He displays temper tantrums at home and school around transitions and behavioral expectations and has complained of feeling "different" and misunderstood by peers in addition to having difficulty reading social cues. His interests include acting and playing Fortnite and other video/computer games. His screen time is limited to 1 to 2 hr/d by the family.As the new clinician, you raise the possibility of undiagnosed autism spectrum disorder as a unifying/underlying diagnosis with his mother, who disagrees and does not consent to additional workup despite your recommendations. How would you proceed with next steps to best support your patient and his family in obtaining further clarifying evaluation?

"Footprints in the Bathroom": The Role of Spirituality in Patient Diagnosis.

CASE: Lucy is a 12-year-old Latina whose mother brought her to the pediatric clinic for help with her anxiety symptoms, "hearing voices," and episodes of "spacing out." Lucy did not cry at birth secondary to vocal cord paralysis and still has the tracheostomy performed at a few days of life. In addition to her neonatal intensive care unit stay, she has been hospitalized for pneumonia. Her mother says she is "sickly" and has a weak immune system due to her asthma symptoms. Lucy also experiences somatic complaints related to gastroesophageal reflux and constipation.Lucy is described as being "in another world" and must be called several times before she responds. Lucy states she is nervous "all the time" and often experiences a fast heartbeat, chest pain, and headache. Her attention and internalizing problems began at age 4 years and have worsened since she entered adolescence. When she is alone in the dark, she sees an unknown person and becomes frightened. She hears the voice of her paternal uncle telling her something will harm her mother and runs crying to "check" on her. Lucy also says she hears voices of paternal family members fighting. She has dreamed that her paternal uncle stabbed her in an alley. Lucy reports experiencing sadness and feelings of wanting to die. She has not tried to harm herself and has no plan to do this. She states that she does not know when she is awake or asleep and "hate people talking in my head." She does not report drug use.Lucy's family is bilingual, English and Spanish. Her mother works part-time as a nutritionist, and her father is a machinist. Her father receives counseling for anger management, and there have been previous unsub- stantiated child abuse reports involving Lucy and her younger brother. The maternal uncle has been involved in a gang and attempts to phone Lucy's mother, who does not wish to have contact with him. Lucy's mother expresses strong Christian religious and spiritual beliefs, including demons and spirits that may enter her home and can be cast off with prayer. Recently, the family purchased a "cuadro" (picture) at a yard sale, and Lucy's mother said this resulted in footprints in the bathroom that are disappearing with prayer, guidance from the church minister, and discarding of the "cuadro."The primary pediatrician ordered a home school program, given Lucy's frequent illnesses. She is progressing well with a special education teacher. Her recent psychological evaluation at school showed a below average nonverbal intelligence quotient, with strengths in the areas of perceptual, logical, and abstract relationships. Lucy's mother in the past has been hesitant to follow through with psychiatric evaluation because "it is up to God."In the clinic, she is pale and slender with an ethereal look. She is awake and alert with appropriate affect and mentation. Her tracheostomy is intact without any respiratory distress noted. There are no signs of drug use or active hallucinations. You are left wondering whether these voices need psychiatric management.

Growth-and Documentation-Deficits: Where To Start in Helping Families.

CASE: Pedro is a 2-year 7-month-old boy who was presented for the first time after a visit to a local emergency room (ER) for diarrhea. At the time of his birth, his undocumented mother, Clara, was 20 years old, uninsured, and with limited English proficiency living approximately 400 miles south of our practice in a different state. Although she had been brought to the United States as a child, she had never finished high school. Pedro was born what mother thought was full-term at his parent's home, where a lay midwife assisted during the delivery. Pedro was not brought to a medical facility at birth; therefore, neither medical nor legal documentation of his birth in the United States, or elsewhere, existed.After enduring 4 years of ongoing verbal and physical abuse, Clara fled to her maternal aunt in our community. The child's initial exposure to medical care was during the emergency visit, which ended up in referral to us. The ED physician suggested that the child visit a primary care physician, but establishment of pediatric care was not made until months later. The child received his first vaccines and immediately was referred to the Growth and Nutrition clinic due to mild wasting and stunting based on Waterlow criteria.Pedro speaks both English and Spanish and has no 2-word combinations and a 50-word combined vocabulary in English and Spanish. In addition, a complete blood count was consistent with iron deficiency anemia, but both sickle cell and G6PD screening are negative.The nutritionist from the specialty clinic obtained a detailed history including overall appetite, feeding skills, meal plans, and eating environment noting that the child was a competent finger feeder. The family's meals were distributed throughout the day as a meal at home and a shared fast food meal while accompanying mother, as she worked as a hair stylist 6 days per week. In addition, the diet is supplemented by ricewater mixed with sugar and ground carrots throughout the day.Where would you head next?REFERENCE1. Waterlow JC. Classification and definition of protein-calorie malnutrition. Br Med J. 1972;3:566-569.

Autism Spectrum Disorder and Avoidant/Restrictive Food Intake Disorder.

CASE: Kendra is a 4-year-old girl with autism spectrum disorder (ASD) who presents for follow-up of feeding problems to her pediatric clinician. She is an only child in a family where both parents are scientists. Feeding concerns date to infancy, when she was diagnosed with Gastroesophageal Reflux Disease (GERD) associated with persistent bottle refusal and the acceptance of few pureed foods. At 13 months, milk and peanut allergies were diagnosed. Following a feeding clinic evaluation at 24 months, she was prescribed a soy milk supplement and an H2 blocker. There was no concern for oral-motor dysfunction. She was also referred to early intervention for feeding therapy. However, her parents terminated participation after 6 months because she became anxious and had tantrum prior to treatment groups.She was seen in another feeding program at 3 years; zinc, folate, thyroid, and a celiac panel were normal, and an endoscopy was negative for eosinophilic esophagitis. She began individual feeding therapy, where concerns for rigidity, difficulty transitioning, and limited peer interactions led to a neuropsychological evaluation. Kendra was diagnosed with an ASD and avoidant/restrictive food intake disorder (ARFID). Her cognitive skills were average, and expressive and receptive language skills were low average.Her diet consisted of French fries, Ritz crackers, pretzels, and 32 ounces of soy formula daily. She had stopped accepting Cheerios and saltines 2 months prior. She controlled other aspects of feeding, insisting on a specific parking spot at a fast food restaurant and drinking from a particular sippy cup. Her parents accepted these demands with concern about her caloric intake, which they tracked daily.Following diagnosis with ARFID, she resumed feeding therapy using a systematic desensitization approach with rewards. At the first session, she kissed and licked 2 new foods without gagging. Her mother appeared receptive to recommendations that included continuing the "food game" at home, replacing 1 ounce of soy formula by offering water each day, limiting between-meal grazing, and refusing specific feeding demands.Currently, her parents plan to discontinue feeding therapy with concerns that the treatment was "too harsh." Her father produces logs of her caloric and micronutrient intake as evidence that she did not replace missed formula with other foods and reports that she subsequently became more difficult to manage behaviorally. Her father now demands to see randomized controlled trials of feeding therapy approaches. Her weight is stable, but she has now limited her pretzel intake to a specific brand. How would you approach her continued care?

Growth--and documentation-deficits: where to start in helping families.

REFERENCE: Pedro is a 2-year 7-month-old boy who was presented for the first time after a visit to a local emergency room (ER) for diarrhea. At the time of his birth, his undocumented mother, Clara, was 20 years old, uninsured, and with limited English proficiency living approximately 400 miles south of our practice in a different state. Although she had been brought to the United States as a child, she had never finished high school. Pedro was born what mother thought was full-term at his parent's home, where a lay midwife assisted during the delivery. Pedro was not brought to a medical facility at birth; therefore, neither medical nor legal documentation of his birth in the United States, or elsewhere, existed.After enduring 4 years of ongoing verbal and physical abuse, Clara fled to her maternal aunt in our community. The child's initial exposure to medical care was during the emergency visit, which ended up in referral to us. The ED physician suggested that the child visit a primary care physician, but establishment of pediatric care was not made until months later. The child received his first vaccines and immediately was referred to the Growth and Nutrition clinic due to mild wasting and stunting based on Waterlow criteria.Pedro speaks both English and Spanish and has no 2-word combinations and a 50-word combined vocabulary in English and Spanish. In addition, a complete blood count was consistent with iron deficiency anemia, but both sickle cell and G6PD screening are negative.The nutritionist from the specialty clinic obtained a detailed history including overall appetite, feeding skills, meal plans, and eating environment noting that the child was a competent finger feeder. The family's meals were distributed throughout the day as a meal at home and a shared fast food meal while accompanying mother, as she worked as a hair stylist 6 days per week. In addition, the diet is supplemented by rice water mixed with sugar and ground carrots throughout the day.Where would you head next?