How Common is Restless Legs Syndrome in Children?

Patient Presentation
A 6-year-old male came to clinic for intermittent leg pain. He described it as an achy pain in both of his lower legs. He would motion with his hands up and down his shins when describing where the pain was. This occurred over the past several months, but had happened twice in the past week so his mother brought him in. The episodes occurred for several minutes but the family was unsure of the duration. It occurred in the evening but did not awaken the boy from sleep. His mother said that he would move or twitch his legs intermittently. There were no specific changes with exercise and he wanted to rest more when the pain occurred.. He had a normal gait and could participate in all activities. He had no limp and denied any other pains including headache. He denied any specific trauma. Doing nothing, rubbing the legs or a warm bath improved his discomfort.

The past medical history revealed an active boy who had a tibial toddler’s fracture from a fall at 3 years of age. The review of systems showed no weight loss, fevers, sweating, bruising/bleeding, specific joint or muscle pain, edema, skin rashes or other lesions or masses, nor any visual problems.The family history was positive for a maternal aunt and grandmother with restless legs syndrome. There were no other parasomnias though.

The pertinent physical exam showed a healthy appearing boy with growth parameters in the 75-90%. He had gained ~1800 grams over the past 9 months. His extremities had 1 shin bruise on his mid-shin. His legs appeared symmetric with good muscle bulk. His muscle tone and strength was normal in his lower extremities. He had full range of motion in both lower extremities without eliciting any pain. There was no edema. His pelvis, spine and upper extremities were normal. His examination was otherwise normal including only a few shotty anterior and inguinal nodes.

The diagnosis of bilateral intermittent leg pain consistent with growth pains was made. The pediatrician discussed the natural history of the problem, and recommended that they continue to treat him symptomatically and monitor him. “Kids can have restless legs syndrome and often it is hard to diagnose, but I feel pretty confident that this isn’t restless legs syndrome. Usually that is in only one leg and the kids want to move and not sit around. They also have less actual pain. He complains of both legs, wants to rest and has mainly pain when he describes it which is consistent with growing pains,” the pediatrician explained. At his next health supervision visit his mother reported that he had had a few other episodes but none that were different. His examination at that time was also normal.

Discussion
Restless legs syndrome (RLS) is also known as Willis-Ekbom disease.
RLS is a clinical diagnosis with criteria being:
1. An urge to move the legs usually accompanied by uncomfortable and unpleasant sensations in the lower extremities (Note: sometimes other body parts can be affected)
2. The urge to move begins or worsens when sitting or lying down
3. The urge to move is partially or totally relieved by movement (Note: relief by activity may not be noticable if severely affected but must have been previously present)
4. The urge to move the legs and any accompanying unpleasant sensations during rest or in activity only occur or are worse in the evening or night then during the day. (Note: worsening may not be noticable at night if severely affected but must have been previously present)
5. The symptoms are not accounted for by another primary medical or behavioral condition.

There must be a significant impact on sleep, cognition, mood, and/or behavior (especially in school or homelife) to make the diagnosis. For adults, all 5 criteria must be met. For children, all must be met but there are caveats depending on timing, severity and the child’s own cognition and language development. The descriptive words must be from the child themself and not the parent. Words children and adolescents use to describe their symptoms include: “boo-boos,” “oowies,” “creepy,” “crawly,” “tingling,” “tickle,” “spider in the legs,” “ants crawling and aching feeling,” “fidgety, restless, too much energy,” “legs need to stretch,” and “want or need to move.” Other criteria that supports the RLS diagnosis is periodic leg movements in sleep > 5 per hour or family history of the same, or a family history of RLS or PLMD in first-degree relatives.

Periodic leg movements in sleep (PLMS) can be associated with RLS but also is a separate entity. PLMS are periodic limb movements that are repetitive, stereotypical limb jerks. Episodes last from 0.5-10 seconds and are separated by 5-90 second intervals. When PLMS of more than 5 times/hour occurs along with sleep disturbance, this is called Periodic leg movements disorder (PLMD). There is considerable overlap with these entities and RLS supersedes the others. Therefore, “[i]t is possible to have a diagnosis of RLS with PLMS but not RLS and PLMD.” It is also possible for PLMD to precede RLS.

RLS may be unilateral or bilateral and although pain can be described by children it is not the main feature. Common mimics of RLS in children includes bruises, dermatitis, growing pains (very common, but is bilateral and pain is a main feature), myalgia/muscle soreness, positional discomfort, tendon/ligament strain or sprain, and transient nerve compression/numbness. Less common problems include arthritis, complex regional pain syndrome, leg cramps, myopathy, peripheral neuropathy, orthopaedic problems, radiculopathy, and sickle cell disease.

The exact cause of RLS is not known but it appears that genetics which involve the dopaminergic pathway are involved. Iron sores also appear to be part of the problem as well. RLS has been associated with other co-morbidities including attention deficit hyperactivity disorder, migraine headache, mood disorder and sleep disorders.

Iron therapy has been shown in some studies to be beneficial. Amount and length of treatment varies. Good sleep hygiene with appropriate room environment (relaxing, quiet, only for sleeping, no screens, etc.), consistent bed time, refraining from alcohol, tobacco or other medications that can cause sleep disruption are all advised. Regular exercise and good nutrition also are advised. There are medications for RLS for adults mainly dopaminergic medications.

Learning Point
RLS is estimated to affect 2-4% of children and adolescents. The number is likely to be an underestimate because of underrecognition by patients, families and health care providers, overlap with many other mimics, and difficulty in language used to describe symptoms by the children and adolescents. It is estimated that 25% of adults had onset of symptoms as a child or teenager. In adults RLS has an estimated prevalence of 4-10%

Questions for Further Discussion
1. What are indications for sleep studies? A review can be found here

2. What causes muscle cramps? A review can be found here

3. List some pediatric parasomnias. 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: Restless Legs and Sleep 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.

Picchietti DL, Bruni O, de Weerd A, Durmer JS, Kotagal S, Owens JA, Simakajornboon N; International Restless Legs Syndrome Study Group (IRLSSG).
Pediatric restless legs syndrome diagnostic criteria: an update by the International Restless Legs Syndrome Study Group. Sleep Med. 2013 Dec;14(12):1253-9.

Simakajornboon N, Dye TJ, Walters AS. Restless Legs Syndrome/Willis-Ekbom Disease and Growing Pains in Children and Adolescents. Sleep Med Clin. 2015 Sep;10(3):311-22, xiv.

Angriman M, Cortese S, Bruni O. Somatic and neuropsychiatric comorbidities in pediatric restless legs syndrome: A systematic review of the literature. Sleep Med Rev. 2017 Aug;34:34-45.

Munzer T, Felt B. The Role of Iron in Pediatric Restless Legs Syndrome and Periodic Limb Movements in Sleep. Semin Neurol. 2017 Aug;37(4):439-445.

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

What Causes Facial Nerve Palsy?

Patient Presentation
An 11-year-old female’s mother called clinic to ask when Bell’s palsy resolves after having pneumonia. After talking with the mother on the telephone a clinic appointment was recommended. The girl had been seen about 3 weeks previously for an upper respiratory tract infection. She was restarted on her albuterol for her intermittent asthma. Two days later she returned because of ear pain and was diagnosed with left otitis media and treated with antibiotics. She was also still wheezing so a course of oral prednisone was prescribed. She was seen 1 week later at an outside urgent care facility when she was visiting relatives because of continued cough. She was diagnosed with walking pneumonia and was started on azithromycin and given another course of oral prednisone. The mother said she had noticed left eye drooping around the time that the otitis media was diagnosed but hadn’t brought it up at the visit. She had looked up the problem on the Internet and wasn’t too concerned. The eyelid drooping became worse over the next several days and then proceeded to improve. The mother took daily pictures which showed this progression and at its worse the eyelid covered about half of the normal opening. The girl said she never had any eye or facial pain, she continued to eat and drink pretty normally and didn’t have problems with speech. As she had missed several days of school because of her illnesses, the mother said no one else really noticed. The girl interjected that one of her friends had said something briefly, but no one else. They denied any other recent viral illnesses. She was only using her albuterol before bed and for exercise at that time.

The past medical history was positive for mild intermittent asthma that was worse with viral upper respiratory tract infections that required oral steroids approximately 1-2 times/year. She had a history of herpes labialis at 6 years of age, but no outbreaks since that time. The family history was positive for migraine and heart disease. The review of systems was otherwise negative.

The pertinent physical exam showed a well-appearing female with normal vital signs, who occasionally had a very mild cough in the office. Her vision was 20/20 in both eyes. HEENT showed very mild left ptosis compared to right side that would be hard to discern without prior pictures of the patient. She could lift her eyebrows and forehead, move her cheeks, mouth and clench her teeth. Her extraocular movements were intact with normal pupillary response. She could keep her eyes tightly closed, but it was slightly easier to open them on the left than right. Her left ear showed a small amount of amber colored fluid at the base. Her lungs were clear. The rest of her examination, including a full neurological examination was negative.

The diagnosis of resolving Bell’s palsy was made. As she had what appeared to be a short duration of symptoms and significant resolution already, plus two courses of steroids and not appear to have any other deficits, the patient was sent home for continued monitoring. Her other symptoms were also markedly improved.

Discussion
Facial nerve palsy has been known for centuries, but in 1821 unilateral facial nerve paralysis was described by Sir Charles Bell. Bell’s palsy (BP) is a unilateral, acute facial paralysis that is clinically diagnosed after other etiologies have been excluded by appropriate history, physical examination and/or laboratory testing or imaging. Symptoms include abnormal movement of facial nerve. It can be associated with changes in facial sensation, hearing, taste or excessive tearing. The right and left sides are equally affected but bilateral BP is rare (0.3%). Paralysis can be complete or incomplete at presentation. All ages can be affected but there are increased risks in the 15-45 year age group and those with diabetes, immunodeficiency or are pregnant.

Etiology is specifically unknown but felt to be caused by facial nerve edema and nerve entrapment. Some theorize that reactivation of herpes simplex virus is a cause. Symptoms tend to peak about 72 hours after onset, and can be graded by the House-Brackmann facial nerve grading system which is:

I. Normal
II. Mild dysfunction – “Slight weakness noticeable only on close inspection…” No functional impairment
III. Moderate dysfunction – “Obvious but not disfiguring difference between the two sides; no functional impairment…”
IV. Moderately severe dysfunction – “Obvious weakness and/or disfiguring assymetry…” Has functional impairment
V. Severe dysfunction – “Only barely perceptible motion.” Has functional impairment
VI. Total paralysis

Overall resolution in the adult age group is cited at 70% or better, and within the pediatric age group with up to 90-100% resolution. Resolution is usually within a few weeks (around 3-4 weeks) but can be months or longer. Treatment with prednisolone within 72 hours of onset is also associated with improved resolution in adults (age 16+ years) and is considered the standard in the adult population. But there is no randomized controlled trial to date in the pediatric population. A multicentered, randomized controlled trial of prenisolone treatment for children in the emergency department is currently underway with results anticipated in 2020. In adults, treatment with antiviral medication does not appear to make significant differences in outcomes. Physical therapy and/or surgical therapy is sometimes needed.

Problems encountered with BP can include difficulty with speech, drooling, eating, self-image and interpersonal communication issues, and opthalmological problems (e.g. excessive tearing and/or eye dryness). Synkinesia or the abnormal movement of facial muscles during voluntary muscle movement of a different group of muscles, can occur. For example, a person smiles, but their eyelid droops at the same time. It is thought that synkinesia is due to abnormal regeneration and sprouting of facial nerve axons into facial muscle groups during healing. Synkinesis can cause self-esteem issues and social problems but also can be associated with muscle spasms and/or pain.

Learning Point
The differential diagnosis of facial paralysis includes:

  • Idiopathic
    • Bell’s palsy
  • Autoimmune
    • Guillian-Barre syndrome
    • Melkersson-Rosenthal
    • Multiple sclerosis
    • Sarcoidosis
  • Congenital
    • CHARGE syndrome
    • Myotonic dystrophy
    • Poland syndrome
    • Trisomy 13 and 18
    • VACTERL syndrome
    • Nerve or muscle hypoplasia or agenesis
  • Infectious
    • Bartonella henselae
    • Clostridium botulinum
    • Coxsackie
    • Diptheria
    • Fungal infection
    • Enterovirus 70
    • Epstein Barr virus
    • Herpes simplex virus
    • HIV
    • Influenza
    • Larval migrans profundus
    • Leprosy
    • Lyme disease
    • Malaria
    • Meningitis or encephalitis
    • Mumps
    • Otitis media or mastoiditis
    • Polio
    • Rubella
    • Syphilis
    • Tetanus
    • Tuberculosis
    • Varicella (Ramsay Hunt)
  • Metabolic
    • Diabetes
    • Hyperthryoidism
    • Vitamin A deficiency
  • Neoplasm
    • Acoustic neuroma
    • Neurofibroma
    • Hemangioma
    • Rhabdomyosarcoma
    • Muscle or nerve neoplasms
    • Other head and neck benign or malignant neoplasms
    • Metastatic cancers
  • Neurologic
    • Stroke
  • Otologic
    • Cholesteatoma
  • Trauma
    • Barotrauma
    • Birth trauma
    • Basilar or temporal skull fracture
    • Middle ear trauma
    • Head and neck treatment or surgery
  • Other
    • Alcoholism
    • Carbon monoxide
    • Ethylene glycol
    • Hypertension
    • Pregnancy
    • Thalidomide
    • Vascular malformation

Questions for Further Discussion
1. What type of laboratory or imaging evaluation can be considered with a patient who has facial nerve palsy?
2. What causes muscle weakness? A review can be found here
3. What causes pediatric stroke? 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: Bell’s Palsy and Paralysis.

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.

Youshani AS, Mehta B, Davies K, Beer H, De S. Management of Bell’s palsy in children: an audit of current practice, review of the literature and a proposed management algorithm. Emerg Med J. 2015 Apr;32(4):274-80.

Vakharia K, Vakharia K. Bell’s Palsy. Facial Plast Surg Clin North Am. 2016 Feb;24(1):1-10.

Babl FE, Mackay MT, Borland ML, Herd DW, Kochar A, Hort J, et.al. ; PREDICT (Paediatric Research In Emergency Departments International Collaborative) research network. Bell’s Palsy in Children (BellPIC): protocol for a multicentre, placebo-controlled randomized trial. BMC Pediatr. 2017 Feb 13;17(1):53.

Babl FE, Gardiner KK, Kochar A, Wilson CL, George SA, Zhang M, et.al. PREDICT (Paediatric Research In Emergency Departments International Collaborative). Bell’s palsy in children: Current treatment patterns in Australia and New Zealand. A PREDICT study. J Paediatr Child Health. 2017 Apr;53(4):339-342.

Geller TJ. Facial Nerve Palsy in Children. UpToDate. Available from the Internet at https://www.uptodate.com/contents/facial-nerve-palsy-in-children
(rev. 3/7/18, cited 2/25/19).

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

What Causes Temporomandibular Joint Problems?

Patient Presentation
A 17-year-old female came to clinic with complaints of mouth pain and headaches. The pain had occurred bilaterally in her cheeks for most days over the past 1-2 weeks. She denied any throat, mouth or ear pain. She also complained of bilateral, temporal headaches that seemed to go to the back of her head. These had happened 2-3 times over the 1-2 weeks and they improved with acetaminophen or ibuprofen and rest. She wasn’t sure how long either pain lasted. The cheek pain was worse at night but did not awaken from her sleep and were better in the morning. She had noticed that the cheek pain was starting to occur earlier in the day though.

The review of systems was negative for any systemic complaint. She denied any trauma. The social history revealed that she wasn’t sleeping much at night because she was studying for college credit and final examinations. Additional history identified that she was now not doing her usual daily running, was eating more candy when she studied and had started to chew gum. She said that she would chew about 1-2 packs/day starting after school. She also confided that she was biting on her pens or pencils. She denied grinding her teeth. The past medical history showed intermittent tension headaches in the past. There was no dental, neurological or other systemic problems. The family history was non-contributory.

The pertinent physical exam showed a healthy appearing female with normal growth parameters and vital signs. Her facial structures looked symmetrical. There were no abnormalities on palpation of her skull and facial bones. She was able to open her mouth more than 3 cm and could move her jaw laterally about 8 mm. This did elicit pain in the temporomandibular joint area at the extremes of movement as did clenching her teeth. Her pharynx looked normal and tapping teeth did not elicit any pain. Her ears were normal as was her neck. The rest of her examination was negative including her neurological examination.

The diagnosis of muscle pain due to overuse was highly suspected as no other obvious pathology could be found. The pediatrician recommended that she stop chewing gum and biting pencils. He also recommended that she try to do at least some physical exercise every day as a way to help with her stress. “I know you don’t think you have lots of time, but you will feel much better and be more productive when you do your studying. Instead of chewing candy, how about drinking water or another low-calorie beverage. You can also use a squishy ball, play dough or something else in your hand to fidget with if you want. Getting up often will also help your studying because you need a break. I’d recommend that you check your chair and posture so you don’t hurt your other muscles too. Do you have a good light? You need one when you are studying,” he counseled. He also recommended that she could use some acetaminophen or ibuprofen if needed for acute pain. “If this is getting worse or not improving in a few days, then I think you should see your dentist,” he also recommended.

Discussion
The mandible normally grows in a symmetric downward and forward movement relative to the skull base. The condyle is the primary growth center. “The mandible is unique in that its 2 joints and growth centers function together as a single unit.” It is the last bone in the body to reach skeletal maturity. The mandible and its growth are important for maxillary growth and therefore many problems that affect the mandible affect the facial and skulls structures as well. These growth problems can be relatively insidious and therefore may need monitoring over longer periods of time such as patients with underlying congenital problems, systemic illnesses or condylar trauma.

Temporomandibular joint disorders (TMJ) are a group of craniofacial pain problems that commonly present with pain, restricted or abnormal movement or sounds during motion. TMJ problems are broadly classified as articular or joint problems, masticatory muscle disorders, headache disorders or associated structure disorders. Problems can occur at any age but prevalence in the pediatric age group increases with age. Some studies report 5-10% for children with mixed dentitia and 5-33% for adolescents.

Physical examination should be performed to help elucidate the problems but specialist help may be necessary such as dental or otolaryngological consultation. Facial symmetry and jaw movement should be inspected. Palpation of the TMJ during mouth opening, closing, lateral movements and clenching of the jaw should be evaluated. Palpation of the various muscles also helps with evaluation. Close inspection of the oral structure including the posterior pharynx and dentitia (including tapping of the teeth to try to elicit individual tooth problems) is appropriate. Range of motion is accessed by measuring distances. The normal vertical interincisal opening is 35-55 mm in adults, whileless than 25-30 mm is abnormal. Lateral movement is normally 8-9 mm (about the size of the mandibular central incisor). One study of 3-5 year olds found a maximal vertical opening of 40 mm, lateral movement of 6.5 mm, and protrusive excursion of 6 mm.
Clicking or crepitus on exam should be noted.

Non-surgical treatment is usually a combination of patient education, behavioral intervention, physical therapy and pharmacotherapy. Families need to be educated about the particular problem and then have a reasonable home care plan to include avoiding irritating movements (avoiding hard or chewy foods, taking small bites, chewing on both sides of the mouth, avoiding chewing gum, clenching the jaw or tongue thrusting), using warm or cold compresses, and keeping the jaw in a neutral position (i.e. teeth apart and masticatory muscles relaxed). Therapy to help with awareness of some contributing behaviors such as relaxation training, biobehavioral or biofeedback and cognitive behavioral therapies can be used. A variety of physical therapies can be tried including massage, manipulation, and ultrasound. Customized appliances to help stabilize or position oral structures can also provide relief as can a variety of anti-inflammatory and other pain medications. Treatment for underlying and co-morbid problems such as arthritis, headaches and acquired or congenital structural abnormalities obviously need to be addressed and they are key to the treatment plan. These may involve more invasive treatment including surgeries.

Learning Point
A differential diagnosis of TMJ problems includes:

  • Fracture or trauma
  • Joint or bone problems
    • Arthralgia
    • Arthritis (particularly juvenile rheumatoid arthritis) and other arthritides and systemic diseases
    • Disc problems
    • Infection – septic joint, postinflammatory
    • Hypomobility – ankylosis, adhesion/adherence, intercondylar reabsorption
    • Hypermobility – subluxation, dislocations
    • Neoplasms
    • Osteocondritis
    • Synovial problems
  • Muscle problems
    • Hypertrophy
    • Myalgia
    • Myositis
    • Myofascial pain with spreading, referred or due to systemic disease/illness
    • Movement problem – orofacial dyskinesia, oromandibular dystonia
    • Muscle or tendon contracture
    • Occlusal problems
    • Overuse problems
    • Tendonitis
  • Congenital disorders
    • Aplasia
    • Hypoplasia
    • Hyperplasia
    • Syndromic including overgrowth syndromes
  • Other
    • Conversion disorder
    • Psychosocial problems
    • Headache – usually tension
    • Movement disorders – muscular dystrophy, Bell’s palsy etc.
    • Neuropathic pain – Fabry’s disease, complex regional pain syndrome, cancer, herpes zoster, HIV
    • Iatrogenic – radiation therapy

Questions for Further Discussion
1. What are indications for consultation with a dentist?
2. What are indications for consultation with an otolaryngologist?
3. What causes dental pain?
4. How is bruxism treated?

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: Jaw Injuries and 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.

Bender ME, Lipin RB, Goudy SL. Development of the Pediatric Temporomandibular Joint. Oral Maxillofac Surg Clin North Am. 2018 Feb;30(1):1-9.

Horswell BB, Sheikh J. Evaluation of Pain Syndromes, Headache, and Temporomandibular Joint Disorders in Children. Oral Maxillofac Surg Clin North Am. 2018 Feb;30(1):11-24.

Scrivani SJ, Khawaja SN, Bavia PF. Nonsurgical Management of Pediatric Temporomandibular Joint Dysfunction. Oral Maxillofac Surg Clin North Am. 2018 Feb;30(1):35-45.

Galea CJ, Dashow JE, Woerner JE. Congenital Abnormalities of the Temporomandibular Joint. Oral Maxillofac Surg Clin North Am. 2018 Feb;30(1):71-82.

Chouinard AF, Kaban LB, Peacock ZS. Acquired Abnormalities of the Temporomandibular Joint. Oral Maxillofac Surg Clin North Am. 2018 Feb;30(1):83-96.

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

What Causes Macrocephaly?

Patient Presentation
A 4-month-old male came to clinic for his health maintenance visit. His parents had no concerns. He was smiling, rolling over, cooing and interacting with people. He was exclusively breastfed. The past medical history showed a full-term infant born without complications around the 50% for weight and length but larger for head circumference (= 36 cm, 85%). The family history was positive for a 3 year old sister with a larger head but no records were available.

The pertinent physical exam showed a happy infant with weight 7.795 kg (75-90%), length 64.5 cm (75%) and head circumference was 44.5 cm (>90%) using World Health Organization growth charts. At 2 months his head circumference had been 40.5 cm (75-90%) for a growth velocity of 2 cm/month for the previous 2 months. His anterior fontanel was 1 cm and flat, and he had no plagiocephaly. Cranial nerves were normal with good tone and strength. He had no head lag. Deep tendon reflexes were +2/+2. The rest of his physical examination was normal.

The diagnosis of a healthy infant with an enlarging head but normal physical examination and development was made. His father’s head circumference was 60 cm (>90%) and his mother’s was 58 cm (>90%). The diagnosis of presumed familial megalencephaly was made with this information. The family was given tape measures and shown how to measure the infant’s head. They did this weekly over the next 6 weeks and the growth velocity was ~0.25 cm/week. Re-evaluation at 6 months of age again showed a healthy male infant with normal development and a head circumference of 46.5 cm (90%). At 9 months of age his head circumference was 47.5 (again 90%) and he continued to be physically and developmentally normal.

Discussion
“Macrocephaly is defined as [an occipitofrontal circumference or head circumference, OFC ] of > 2 standard deviations above the mean or above the 97th percentage for a given age, and gender, or when serial measurement shows progressive enlargement, crossing of one or more major percentiles, or when there is an increase in OFC > 2 cm/month in the first 6 months of life.” Megalencephaly is enlargement of the brain parenchyma. The OFC should be measured using a non-elastic tape which surrounds the head along the line of the glabella and posterior occipital protrusion.

There are ethnic differences for head circumferences so the growth chart that best matches the child’s family heritage should be used. A review of the best growth charts can be found here.

General averages for OFC increase are:

  • Average at birth = ~35 cm
  • 0-3 months = 2 cm/month (average 3 month old is ~ 41 cm)
  • 0-1 year = 1 cm/month (average 1 year old is ~ 47 cm)
  • > 1 year = only another 8 cm total (average adult is ~ 55 cm)

A review of the other growth parameters can be found here.

Patients should be evaluated for developmental delay, signs of intracranial infection or trauma, syndromic features, and family history of cutaneous or neurological abnormalities. Children with non-full fontanels, normal mentation and no signs of developmental delay are more likely to have familial, isolated or benign enlargement of the subarachnoid space. Changes in mentation, developmental delay and full fontanels are more likely to have a serious cause of hydrocephalus.

More evaluation may be necessary if abnormalities are found on history and physical exam and should guide that evaluation such as cranial ultrasound or other imaging depending on age and circumstances, bone radiographs, or metabolic evaluation (e.g. Vitamin D level).

Learning Point
The differential diagnosis of macrocephaly includes:

  • Brain parenchyma enlargement
    • Familial/genetic – parents/family also with macrocephaly in an otherwise normal child (63.3%)
    • Isolated – parents and family without macrocephaly in an otherwise normal child (20%)
    • Genetic
      • Autism spectrum disorder (1.1%)
      • Bone dysplasia – achrondroplasia (1.1%), hypochrondroplasia(1.1%)
      • Fragile X – OFC may be enlarged but may not be > 2 standard deviations
      • Neurocutaneous disorders – neurofibromatosis, tuberous sclerosis
      • Overgrowth disorders
    • Metabolic diseases
      • Gangiosidosis
      • Leukodystrophies
      • Rickets (1.1%)
  • Increased cerebrospinal fluid
    • Benign enlargement of the subarachnoid space (BESS or benign external hydrocephalus) (2.2%)
    • Choroid plexus cyst (1.1%)
    • Hydrocephalus – obstructive or communicating (8.9%)
  • Increased blood
    • Subdural hematoma
    • Arteriovenous malformation
  • Increased intracranial pressure
    • Pseudotumor cerebri
    • Infection
    • Inflammation
    • Vitamin A deficiency or excess
  • Bone enlargement
    • Thalassemia
    • Bone dysplasia
  • Masses
    • Brain tumor
    • Arteriovenous malformation

Note: Number in parentheses is from a 2018 study of 90 Turkish children in a well child clinic. Many other studies are from referral clinics such as neurology, neurosurgery or developmental disabilities which will cite different numbers that correspond to their referral population.

Questions for Further Discussion
1. What are the causes of microcephaly? A review can be found here.

2. What are causes of a bulging anterior fontanel? A review can be found here.

3. When do the fontanels normally close? here 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: Brain Malformations

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.

Tucker J, Choudhary AK, Piatt J. Macrocephaly in infancy: benign enlargement of the subarachnoid spaces and subdural collections. J Neurosurg Pediatr. 2016 Jul;18(1):16-20.

Kurata H, Shirai K, Saito Y, Okazaki T, Ohno K, Oguri M, Adachi K, Nanba E, Maegaki Y. Neurodevelopmental disorders in children with macrocephaly: A prevalence study and PTEN gene analysis. Brain Dev. 2018 Jan;40(1):36-41.

Yilmazbas P, Gokcay G, Eren T, Karapınar E, Kural B. Macrocephaly diagnosed during well child visits. Pediatr Int. 2018 May;60(5):474-477.

Boom JA. Macrocephaly in infants and children: Etiology and evaluation. UpToDate. (rev. 12/8/2017, cited 2/4/2019).

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