What Are the Clinical Characteristics of the Most Common Skeletal Dysplasia?

Patient Presentation
A 4-year-old female came to clinic for her health maintenance examination. She had achrondroplasia and a history of otitis media but was otherwise well. She was doing well in preschool and there were no specific questions or concerns. The family history showed that her achondroplasia was from a new genetic mutation.

The pertinent physical exam showed a smiling female who was < 5% of length, but with 25% for weight and head circumference. She had shorter limbs with some lumbar lordosis with a relatively larger head and shortened neck. She had some otosclerosis bilaterally. Otherwise her examination was normal.

The diagnosis of a well preschooler with achondroplasia was made. The pediatrician remarked that he had re-reviewed some of the potential problems for patients with achrondroplasia before she came to the office. “You said she’s keeping up with the other kids and not having any problems moving as some patients have problems with their joints or low muscle tone, so I would continue to watch for this. Some patients also can have some lung problems too. Just watch out to see if she is having any problems breathing when she is playing or sleeping. If you think so, let me know right away,” he advised.

Discussion
With more than 200 skeletal dysplasias and multiple variations even for one dysplasia, it can be difficult for the general practitioner to know a lot of specific information about all the skeletal dysplasias. Achondroplasia (ACP) is the most common skeletal dysplasia and specifically short-limbed dwarfism. The incidence is about 1 in 15-40,000 live births. ACP is autosomal dominant with about 80% arising from new mutations with a single nucleotide substitution in the fibroblast growth factor receptor 3 (FGFR3) gene on chromosome 4. This gene regulates the conversion of cartilage to bone, with the problem showing up after 22 weeks gestation. Therefore 2nd trimester fetal ultrasounds often will be normal.

Osteogenesis imperfecta (OI) is a connective tissue disorder (most commonly autosomal dominant) which may have skeletal dysplasia as well (some lethal variations). Classic OI has increased bone fragility and increased fractures. Fractures may be with no or minimal trauma and may occur in atypical locations. Severe forms can have fractures occurring in utero. Bony deformations and reduced bony growth can cause a variety of clinical problems including scoliosis and long-bone bowing. Problems which may overlap with ACP include hypermobility, muscle weakness, hearing loss, reduced pulmonary function and complications. Cardiovascular problems are also common with valvular dysfunction and aortic root dilatation. Dental dysplasia and abnormal coloration and bluish sclera may be seen as well.

Learning Point
Classic achondroplasia has the following clinical phenotype:

  • Shortened extremities particularly femur and humerus
  • Shortened fingers referred to sometimes as a trident hand
  • Facial features which have frontal bossing and midline facial hypoplasia
  • Shortened neck
  • Long trunk with lumbar lordosis
  • Hypotonia
  • Joint hypermobility
  • Normal intelligence but may have some gross and fine motor developmental delays
  • Redundant skin on extremities

As a result, patients have or may have:

  • Overall short stature – average adult height is around 132 cm in males, 124 cm in females. Most height loss occurs in first 2 years of life
  • Small foramen magnum and spinal canal cause compression of the spinal cord
    • Increased sudden infant death syndrome in this patient population may be because this is unrecognized
    • Hydrocephalus
  • Restrictive pulmonary disease
    • Obstructive sleep apnea
  • Gastroesophageal reflux disease
  • Otitis media with increased hearing and speech problems
  • Obesity
  • Mental health problems including body image
  • Increased mortality especially in first few years of life

There are several lethal dysplasias that present similarly to ACP. Homozygous ACP itself is lethal. Non-lethal dysplasias that are similar include chrondroplasia puncta, diastrophic dysplasia and spondyloepiphyseal dysplasia congenita. If the patient looks like they have ACP but has other congenital anomalies, other skeletal dysplasias should be considered as well. For patients with shortened limbs, other similar conditions include osteogensis imperfecta (see above), hypochondroplasia, hypophosphatasia, and thanatophoric dwarfism.

Accurate measurement of limbs to determine if the changes are proportionate or disproportionate are important in making the diagnosis of ACP along with changes on radiographs. Genetic testing can be helpful if the diagnosis is in question or for needed confirmation.

Treatment of ACP usually incudes education and support of the patient and families and monitoring and treatment for underlying problems. More recently growth hormone and C-natriuretic peptide analogs have been in clinical trials to try to increase overall height.

Questions for Further Discussion
1. What information resources do you use to review genetic diseases?
2. What disease- or condition- based patient support groups do you suggest families use?
3. What conditions have an increased risk of otitis media?
4. What is in the differential diagnosis of short stature? A review can be found 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 and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Dwarfism and Growth Disorders.

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.

Daugherty A. Achondroplasia: Etiology, Clinical Presentation, and Management. Neonatal Network. 2017;36(6):337-342. doi:10.1891/0730-0832.36.6.337

Rossi V, Lee B, Marom R. Osteogenesis imperfecta – advancements in genetics and treatment. Curr Opin Pediatr. 2019;31(6):708-715. doi:10.1097/MOP.0000000000000813

Semler O, Rehberg M, Mehdiani N, Jackels M, Hoyer-Kuhn H. Current and Emerging Therapeutic Options for the Management of Rare Skeletal Diseases. Pediatr Drugs. 2019;21(2):95-106. doi:10.1007/s40272-019-00330-0

Hogler W, Ward LM. New developments in the management of achondroplasia. Wien Med Wochenschr. 2020;170(5):104-111. doi:10.1007/s10354-020-00741-6

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

What is Refeeding Syndrome?

Patient Presentation
An 18-year-old female came to the emergency room with a history of restrictive eating for about 6 weeks. She had a history of anorexia nervosa that had been successfully treated with outpatient therapy and she had continued to have counseling sessions monthly while she had been living at home. She had just moved away for college and since living in the dormitory, she found that she was more anxious, concerned about her body image and was starting to fall back into her eating disordered habits. She was eating meals but was not eating as much and was choosing lower calorie items. She had increased her exercise by running 3 miles instead of 2 miles daily. She denied any purging and that had not been part of her habits before either. She had eaten a full dinner the night before and had abdominal pain afterwards. She read online about refeeding syndrome and was worried that she had it. She said that she knew she was slipping back into her old habits and wanted it to stop. She had not yet tried to find a counselor. She said her family was supportive but she wanted to “…do college on my own” and didn’t want to worry them. The review of systems showed some nausea with larger meals, no emesis or diarrhea, and no dizziness or syncope. She was taking a multivitamin.

The pertinent physical exam showed a thin female who was anxious. Her vital signs revealed 88 bpm heart rate, blood pressure of 102/66, respiratory rate of 20. Her weight was 118 pounds which was down 6 pounds from her previous weight per her history. Her physical examination was otherwise normal. The laboratory evaluation included a complete metabolic panel which was normal including calcium, magnesium and phosphorus and potassium. Her complete blood count also showed no evidence of anemia.

The diagnosis of an anxious college freshman with concerns for early relapse of anorexia nervosa was made.
The emergency room physician talked with her about local support services and followup. “All of your laboratory testing looks normal, along with your physical examination. With your symptoms I don’t think you have refeeding syndrome. I think you felt really full because your stomach isn’t used to so much food at once. Thank you for coming today. That means you really want to help yourself and we want to do that too. It can be really hard to move away from home and deal with everything on your own. But look around, adults don’t do everything on their own. We work together. Spouses, family, friends. We all help each other. Right now your usual people are far away, and they can still help, but we need to help you find some people you can trust here too. On campus, the student health center takes care of all kinds of problems and they understand how hard it can be to move away from home. They can help a lot. They can give you some short-term counseling until you can set up an appointment with someone longer-term. They will also help you find that longer-term therapist. They can also take care of any of your medical needs and the follow up you need. If it is okay with you, I can have our social worker help you to make an appointment with student health today before you leave,” the physician offered. The student agreed. By the end of the visit she stated that she was going to call her parents for additional support, and was thinking about possibly confiding in the peer resident assistant in her dorm.

Discussion
Anorexia nervosa is an eating disorder with an intense fear of being overweight (i.e. distorted body image), and self-starvation and excessive weight loss. It is more common in women (1.2%) than men (0.2%) but can be seen in both genders. Risk factors include high-intelligence, perfectionism/inflexibility, anxiety, activities where thinner body types are expected (e.g. dancer, diver, gymnast, long-distance runner, volleyball player, etc.)

Other eating disorders include bulimia nervosa (i.e. cycles of binge eating and then purging), binge eating disorder (i.e. purging), orthorexia (i.e. obsessions with healthful eating), avoidant restrictive food intake disorder, compulsive exercise, laxative abuse, rumination, pica, and unspecified eating disorder. Treatment includes a multimodal approach with appropriate nutritional resuscitation (if needed) and intake, nutritional counseling, mental health counseling and support. Long-term, building skills to develop an appropriate relationship with food is the key, along with building supports to help the patient continue healthy habits.

Learning Point
Refeeding syndrome (RFS) broadly encompasses a severe electrolyte disturbance (principally low serum concentrations of the predominantly intracellular ions; phosphate, magnesium and potassium) and metabolic abnormalities in undernourished patients undergoing refeeding whether orally, enterally or parenterally. In essence, RFS reflects the change from catabolic to anabolic metabolism.”” Hypophosphatemia is considered one of the hallmarks of this process. In general there needs to be low body mass index, unintentional weight loss, minimal or no nutritional intake for a period of time (often 5-10 days) and usually electrolyte abnormalities. One of main problems is that RFS clinical features can be mild, easily overlooked and also can cause sudden morbities and even mortality. RFS prevalence varies widely depending on the group studied and the actual definition used from 0.43%-34%.

Populations at risk for RFS includes:

  • Acute or chronic disease
    • Critically ill
    • Chronic infection – HIV
    • Malignancy
    • Premature infant
    • Pregnancy
    • Prolonged emesis
    • Older age
    • Undernutrition
    • Renal failure
  • Athletes and military recruits as their nutritional intake may not match their need in training
  • Gastrointestinal problems
    • Bariatric surgery
    • Bowel resection
    • Esophageal dysmotility and dysphagia
  • Malabsorption syndrome
    • Inflammatory bowel
  • Mental health disorders
    • Alcohol and substance abuse
    • Eating disorders especially anorexia nervosa
    • Schizophrenia
  • Societal problems
    • Child maltreatment
    • Hunger strike
    • Famine
    • Migration
    • Starvation

Potential signs and symptoms of RFS include:

  • General
    • Fatigue
    • Lassitude
    • Myalgia
  • Cardiac
    • Arrhythmias
    • Congestive heart failure
    • Sudden death
  • Hematology
    • Anemia
    • Thrombocytopenia
  • Gastrointestinal
    • Constipation
    • Nausea
    • Emesis
  • Mental status changes
    • Acute encephalopathy
    • Ataxia
    • Coma
    • Delirium
    • Paresthesia
    • Peripheral neuropathy
  • Metabolic
    • Hyper or hypoglycemia
    • Hypokalemia
    • Hypophosphatemia
    • Hypomagnesemia
    • Fluid overload or dehydration
    • Vitamin and trace mineral deficiencies especially B Vitamins
  • Musculoskeletal
    • Muscle weakness
    • Osteomalacia
  • Renal
    • Acute tubular necrosis
    • Chronic renal impairment
  • Respiratory
    • Respiratory muscle weakness
    • Ventilatory dependency
    • Respiratory failure
  • Other
    • Increased risk for infections

Treatment of RFS like eating disorders requires an inpatient multimodal approach with very careful monitoring of fluid, electrolyte and energy replacement. Other nutritional supplementation is usually needed as well, along with appropriate management of the underlying cause of the RFS.

Questions for Further Discussion
1. What is female athlete triad? A review can be found here
2. What are other causes of some of the electrolyte abnormalities above such as hypophosphatemia or hypokalemia?
see Fluids and Electrolytescases here
3. What anticipatory guidance do you offer to students going off to college?
A review can be found 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 and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Eating Disorders and Fluid and Electrolyte Balance.

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.

Crook MA, Refeeding syndrome: Problems with definition and management. Nutrition 2014;30:1448-1455. doi:10.1016/j.nut.2014.03.026

Silva JSV da, Seres DS, Sabino K, et al. ASPEN Consensus Recommendations for Refeeding Syndrome. Nutrition in Clinical Practice. 2020;35(2):178-195. doi:10.1002/ncp.10474

Gjoertz M, Wang J, Chatelet S, Chaubert CM, Lier F, Ambresin A-E. Nutrition Approach for Inpatients With Anorexia Nervosa: Impact of a Clinical Refeeding Guideline. Journal of Parenteral and Enteral Nutrition. 2020;44(6):1124-1139. doi:10.1002/jpen.1723

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

What Causes Irritability?

Patient Presentation
A 4-month-old male was transferred from an outside emergency room for treatment of a femur fracture. The infant had presented after his mother returned from work and was told that the infant had been irritable for about 2 hours. He had been in the care of her new boyfriend who said that the infant was normal until he became irritated. The boyfriend said he had tried to calm the infant by walking and cuddling but the infant would not calm down. He also had tried a bottle which the infant refused and changing a diaper also did not change the irritability. The mother had noted that the infant became more irritated when he was moved and really irritated when she changed his diaper too. The mother said he had been well when she left him in the morning.

The past medical history showed a full-term infant who had received his routine care and vaccinations. The social history showed that this was the first infant for the mother but the father had 2 other children who were not in his care. The parents were unmarried and the father was working part-time.

In the emergency room, the pertinent physical exam showed an irritated infant who seemed to calm somewhat when he wasn’t being handled. His vital signs were normal with growth percentiles in the 25-50%. HEENT was normal with a flat anterior fontanelle. Heart, lungs, and genitourinary systems were normal. The patient seemed to not want to move his left leg and it appeared more swollen in the femur but he had normal capillary refill, good pulses and normal deep tendon reflexes. The rest of his examination was normal.

The diagnosis of an extremity problem was made and the plain radiograph showed a femur fracture. The patient was placed into a splint and transferred to the regional children’s hospital for treatment and further evaluation of non-accidental trauma.

Discussion
Child abuse or non-accidental trauma is a clinical diagnosis. It is the constellation of history, physical examination, radiographic evaluation, laboratory testing and investigation that determines if child abuse has occurred. Irritability caused by fractures or other trauma can be a presenting symptom of abuse. Fractures can be a presentation but they are also common problems not associated with abuse. Femoral shaft fractures are estimated to account for only 1.6% of all fractures in children, therefore they are potentially more suspicious for child abuse. A review of femur fractures can be found here. A review of non-accidental trauma can be found here.

Learning Point
Irritability has different meanings to different people and in the context they are used. Irritability in the medical sense is thought to be caused by the body being abnormally excited or sensitive causing the child to have exaggerated or excessive crying. The inability to be soothed usually helps to differentiate the child who is more accurately described as fussy or hard to please, bothered or is burdensome or troublesome, or even cranky or ill-tempered and grouchy. An irritable child who is also lethargic (i.e. having abnormal drowsiness or sleepiness) is much more clinically concerning than a child who is fussy and tired or fatigued.
Some problems may be more common in certain age groups but many can be found in all age groups.

The differential diagnosis of irritability includes:

  • Neonatal
    • Normal body sensations – wet, cold, loud noises
    • Arrhythmia and/or heart failure
    • Central nervous system abnormalities
    • Genetic problems
    • Hypoxia or hypoxic ischemic encephalopathy
    • Infection including sepsis and meningitis
    • Neonatal withdrawal syndrome
    • Metabolic problems
    • Inborn errors of metabolism – phenylketonuria, urea cycle defects
    • Pain
  • Young infant
    • Normal body sensations – sleep deprivation, hunger or overfed, too hot or cold, constipation, urinary retention, being wet, loud noises, difficulty breathing, pruritis, fever
    • Arrhythmia and/or heart failure
    • Epilepsy
    • Celiac disease
    • Colic
    • Infection – sepsis, meningitis, otitis media, urinary tract infection, gastroenteritis, pneumonia
    • Metabolic problems
    • Inborn errors of metabolism – phenylketonuria, urea cycle defects.
    • Pain – trauma, reflux, stomatitis, rash/pruritis, corneal abrasion, etc.
    • Teething
  • Older child
    • Normal emotions – angry, annoyed, bored, frustrated, excited, inability to communicate
    • Behavior problems – attention problems, bullying, temperamental mismatch
    • Social insecurity and adverse childhood experiences
    • Normal body sensations – sleep deprivation, hunger or overfed, too hot or cold, constipation, urinary retention, being wet, loud noises, difficulty breathing, pruritis, fever
    • Arrhythmia and/or heart failure
    • Anemia
    • Brain tumor
    • Epilepsy
    • Food intolerance
    • Infection – sepsis, meningitis, otitis media, urinary tract infection, gastroenteritis, pneumonia
    • Metabolic problem – hypoglycemia, hypercalcemia
    • Medications or substance abuse
    • Psychological problems – anxiety or mood problems, mania
    • Pain – trauma, reflux, stomatitis, rash/pruritis, corneal abrasion, etc.
    • Teething

Question for Further Discussion
1. What recommendations do you give for a colicky or crying infant? A review can be found here.
2. What causes lethargy? A review can be found here.
3. What are the criteria for the Glasgow Coma Scale?

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 and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Common Infant and Newborn Problems, Child Abuse, and Fractures.

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.

Sheldon SH, Levy HB. Pediatric Differential Diagnoses, 2nd. Edit. Raven Press, NY, NY. 1985:107-109.

Illingworth RS. Common Symptoms of Disease in Children. 9th Edit. Blackwell Scientific, Oxford, UK.1988;220-21.

Sukhodolsky DG, Smith SD, McCauley SA, Ibrahim K, Piasecka JB. Behavioral Interventions for Anger, Irritability, and Aggression in Children and Adolescents. J Child Adolesc Psychopharmacol. 2016;26(1):58-64. doi:10.1089/cap.2015.0120.

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

What Is In That Ear?

Patient Presentation
A 3-year-old female came to clinic for their health maintenance visit. She had not been seen since her 18 month appointment and the mother had no concerns. The past medical history showed that the child had pressure equalizing tubes placed at 13 months of age for recurrent otitis media but again no followup at the institution had occurred and the mother said the child had been well.

The pertinent physical exam revealed a happy child with normal development who was growing just above the 50th percentiles. She had poor dentitia. Her left tympanic membrane showed no tube and some minor tympanic sclerosis. The right tympanic membrane had no tube in place. The external canal had a pinkish/blue mass just lateral to the tympanic membrane that appeared to be arising from the floor and ventral wall (about 6-8 o’clock.) It appeared glistening and somewhat translucent with the tissue appearing healthy overall. The rest of her examination was normal.

The diagnosis of a healthy female with poor dentitia and an external auditory canal lesion was made. The pediatrician thought that this may be a retained pressure-equalizing tube with overgrowth of the surrounding tissue. This was confirmed by the otolaryngologist who removed the tissue and tube surgically. The external canal healed normally and she did not have any problems with it over the next 1 year.

Discussion
The external auditory canal mainly derives from the ectoderm however it abuts other structures which arise from mesodermal or endodermal tissues. The lateral 1/3 is primarily cartilaginous with the inner 2/3rd being bony with the tympanic, temporal and mastoid bone forming various parts. The canal is lined with squamous epithelium and has various structures such as sebaceous glands, hair follicles and of course ceruminous glands.

It is not surprising that this structure is subject to obstruction given its small size. Cerumen, hair and other cellular debris may become impacted if they are not regularly expelled from the canal through movement of the contents and also through water/soap during washing of the head. Because of mild irritation and/or pressure or decreased hearing, people may also insert foreign bodies to move the cerumen and may cause impaction and/or retention of the object. Children often will explore their bodies and insert small foreign objects into various body parts including the external auditory canal. Complications of cerumen can be reviewed here.

Therefore it is not uncommon that health care providers encounter middle ear obstructions especially cerumen plugs or foreign bodies. Otitis externa is often caused by retention of cerumen and debris and water that is blocked by the debris setting up a usually minor infection but which can be quite painful and may need debridement. A review of otitis externa can be viewed here.

Much less commonly do other lesions occur in the external canal, but because of the location and the multiple types of tissues in the area the lesions have broad origins. Fortunately, most causes are benign and usually do not require extensive treatment.

Reasons that lesions may come to attention include pain, feeling of fullness/pressure, pruritis, hearing loss, tinnitus, otorrhea, bleeding, or visualization of the mass itself.

Learning Point
The differential diagnosis of external ear canal lesions includes:

  • **Cerumen impaction
  • **Foreign bodies
  • Bony tumors
    • Exostosis
    • Osteoma
  • Dermatological problems
    • Cholesteatoma
    • Epidermoid cyst
    • Keratosis obliterans
  • Infectious
    • Papilloma
    • Malignant otitis externa or basilar skull osteomyelitis
  • Neoplastic
    • Benign – most are benign
      • Adenoma
      • Angiofibroma
      • Capillary hemangioma
      • Hamartoma
      • Granuloma
      • Lipoma
      • Neuroma
    • Malignant
      • Langerhans cell histiocystosis
      • Yolk sac tumor
      • Malignant spread

** – most common problems

Questions for Further Discussion
1. What lesions are found on the tympanic membrane or in the middle ear?
2. What causes hearing loss? A review can be found 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 and the Cochrane Database of Systematic Reviews.

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

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.

Spielmann PM, McKean S, White RD, Hussain SSM. Surgical management of external auditory canal lesions. J Laryngol Otol. 2013;127(3):246-251. doi:10.1017/S0022215112003155

Shi H, Tang Q, Zhen T, Li H, Zhang F, Han A. Yolk sac tumor of the external auditory canal: a case report and literature review. Int J Clin Exp Pathol. 2015;8(11):15001-15006.

Luo W, Wu J, Peng KA, et al. Clinical Characteristics of Patients With Papilloma in the External Auditory Canal. The Laryngoscope. 2021;131(5):1132-1137. doi:10.1002/lary.29113

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