oligodontia and skeletal anomalies in a young boy contemporarypediatrics.modernmedicine.com

8/19/2019 Oligodontia and Skeletal Anomalies in a Young Boy Contemporarypediatrics.modernmedicine.com

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Oligodontia and skeletal anomalies in a young boy

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The Case

An 8-year-boy was referred to our skeletal dysplasia center by his dentist for evaluation of possible ectodermal

dysplasia (ED). The dentist noticed small, widely spaced teeth, multiple missing teeth, and the absence of eruption

of secondary teeth. Additionally, the patient’s body mass index (BMI) had been gradually increasing to the 85th

percentile, thereby classifying him as overweight.

History and physical examination

In addition to the patient’s presenting tooth anomalies, a review of systems revealed cold intolerance, constipation,

intermittent calf muscle cramps, and occasional dry skin, although he was able to sweat. (The absence of sweatingwith risk of overheating is a hallmark of ED.)

On examination, the patient was found to have thin, dark, and fine hair; coarse facial appearance; oligodontia with

widely spaced small teeth; webbed neck; darkening of the skin around his neck (consistent with acanthosis

nigricans); short fingers with excess wrinkles; and diffuse muscular hypertrophy (Figure 1). He was short, 119.2 cm

tall (1.2 percentile for age); weight was 26.4 kg (between 25th and 50th percentile); and BMI was at 85th percentile

largely because of his relatively short stature.1 Neck palpation noted a bilateral thyroid enlargement of 3 cm by 1

cm. He had attained all developmental milestones anticipated for his age and was doing well at school. There was

no family history of ED, short stature, or other genetic disease. In addition, there was no history of consanguinity.

A skeletal survey showed a delayed bone age of 4 years 6 months at a chronological age of 8 years 9 months, butno other features of an underlying short stature bone dysplasia were noted, excluding skeletal dysplasia and other

primary disorders as the cause. Also, echocardiogram did not show any evidence of congenital heart disease,

except showing trivial pericardial effusion. Screening laboratory evaluations to investigate the etiology of his short

stature revealed abnormal thyroid stimulating hormone (TSH) at 1302 uIU/mL (normal, 0.5-4.5 uIU/mL) and free T4


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You decide that the patient’s described and observed symptoms can be attributed to the primary or secondary

causes of short stature (Table).2,3

Short stature in children can be defined as height that is 2 standard deviations or more below the mean height for

children of comparable sex, chronological age, and ethnicity. Note that these categories are a general guide to the

etiology of poor growth in children and some may overlap or present concurrently. Also note that constitutional

growth delay and familial short stature may be normal variants of short stature.

Constitutional growth delay is a temporary delay in childhood skeletal growth without other physical conditions

causing the delay. This growth delay resolves as the child enters puberty and he or she typically attains an

“average” height percentile. Familial short stature is characterized by a family history of short stature in an individua

with height below the 3rd percentile despite normal bone age, annual growth rate, and pubertal onset. Primarygrowth disorders that are often unresponsive to treatment include chromosomal anomalies, genetic syndromes, and

skeletal dysplasias. Secondary growth disorders are generally amenable to treatment and include endocrine

conditions (eg, hypothyroidism, growth hormone deficiency) and severe congenital anomalies (eg, structural heart

defect) or disease (eg, cystic fibrosis), which divert energy that should have been used for growth.

When approaching a child with short stature, all these diagnostic categories must be considered and prioritized for

further evaluation. Although not all children with short stature will need treatment or benefit from it, some causes are

reversible and effective treatment can have a dramatic influence on overall health and final adult height.

This patient was referred to our clinic for evaluation of ED. Ectodermal dysplasia is a descriptive diagnosis for a


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collection of heritable conditions characterized by abnormalities of 2 or more ectodermal structures such as the hair

teeth, nails, sweat glands, craniofacial structure, digits, and other parts of body. There are X-linked, recessive, and

dominant forms of ectodermal dysplasia.4 Our patient had sparse hair growth, noneruption of secondary teeth, cold

intolerance, and coarse facial features, but normal sweating and no family history of ED.

With further investigation, it became clear that he had symptoms and signs of acquired autoimmune hypothyroidism

which is a completely reversible condition if treated effectively. Myopathy associated with hypothyroidism classically

presents with proximal weakness, fatigue, exertional pain, slowed movement, diminished deep reï¬exes, stiffness,

and myalgia. Rarely, muscle enlargement is also seen as in this case, and the term Kocher-Debre-Semelaignesyndrome (KDS) is used.

Growth failure may be an early and major manifestation of hypothyroidism in children, often present for several

years before other symptoms occur. The bone age of a patient with hypothyroidism is typically delayed, thus

allowing for reasonably normal growth potential if supplemented with thyroxine. Abnormal physical features of

hypothyroidism include short stature in conjunction with excessive relative body weight (typically nonlean mass);

puffy faces with a dull expression; bradycardia; delayed deep tendon reflexes; and pseudohypertrophy of the

muscles.

Despite their muscular appearance, children with hypothyroidism may actually be weak. The thyroid gland may be

normal in size, not palpable, or diffusely enlarged. Treatment with thyroid hormone results in prompt improvement inmuscle strength and normalization of serum creatinine kinase concentrations, even in infants with longstanding

congenital hypothyroidism.5,6

A diagnosis of attention-deficit/hyperactivity disorder (ADHD) after successful treatment of hypothyroidism is

described in the medical literature.7 It is thought that the primary hypothyroidism leads to a generalized decreased

activity level that suppresses or masks preexisting ADHD in some children. After thyroid replacement, children with

hypothyroidism have normalization of their overall activity and begin to experience significant behavioral problems

and features of ADHD.

Another explanation for this postthyroid-treatment ADHD diagnosis concerns neurotransmitter imbalance.

Decreased receptor sensitivity to central nervous system catecholamines is accompanied by a compensatoryincrease in catechol concentration during hypothyroidism. Rapid normalization after treatment may augment

catechol receptor sensitivity and precipitate a hypercatecholaminergic state.

Diagnosis

Collectively, our patient’s symptoms and investigations were consistent with autoimmune hypothyroidism. Of note,

newborn screening thyroid results had been normal in 3 samples. A secondary diagnosis of KDS was made, based

on the findings of profound acquired hypothyroidism; diffuse muscle pseudohypertrophy; and features of myxedema

including short stature, oligodontia, cold intolerance, constipation, dry skin, and coarse facial features.8,9 Clinical

KDS is a myopathy of hypothyroidism associated with pseudohypertrophy in childhood.10

Treatment and response


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Our patient was treated with levothyroxine supplementation, 25 mcg/day. His dose was adjusted according to TSH

and free T4 levels to a current euthyroid dose of 100 mcg/day (Figure 2).

Height increased from 119.2 cm (1.2 percentile; z score, -2.237) to 138 cm (z score, -1.055) over a 2-year time

period. Concurrent with his height increase, his weight percentile dropped from the 50th percentile at presentation to

the 10th percentile, and his BMI dropped from the 85th percentile to between the 25th and 50th percentiles (Figure

3).

Additionally, his hair grew and the texture changed; his generalized muscular hypertrophy faded; and his mildly


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coarse facial features softened. There also was prompt eruption of secondary teeth (Figure 4).


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After levothyroxine treatment for approximately 6 to 7 months, the patient experienced attention problems and a

decrease in school performance. He was diagnosed with ADHD and treated with Adderall.

Conclusion

Short stature is a general term used for children who are 2 standard deviations or more below the mean height for

children of a particular sex, chronological age, and ethnicity. The diagnosis must be considered in the context of the

child’s inherited genetic potential. Hypothyroidism is a treatable cause of short stature in children that may mimic

other genetic conditions such as ED. When evaluating a child with short stature, it is important to assess

longitudinal growth parameters; complete a history and physical exam, including a family history with particular inquiry of parental height and pubertal timing; and consider normal variants of low growth acquisition (eg, familial

short stature, constitutional growth delay) as well as recognized primary and secondary medical diagnoses.

Not all children with short stature will need treatment or benefit from it. However, some causes are reversible and

effective treatment may allow a child to attain the adult height influenced by midparental height.


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Acknowledgement

We wish to acknowledge the Alan and Kathryn Greenberg Center for Skeletal Dysplasias in the McKusick-Nathans

Institute of Genetic Medicine at Johns Hopkins University, Baltimore, Maryland, for supporting this research. We als

would like to acknowledge the patient and his family who graciously allowed us to present his case.


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2. Rogol AD. Causes of short stature. UpToDate website. http://www.uptodate.com/contents/causes-of-short-

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appropriate (AGA) for gestational age with short-statured parents. J Pediatr . 2006;148(6):747-752.

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Textbook of Pediatrics. 18th ed. Philadelphia, PA: Saunders Elsevier; 2007:2666.

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upon 13 cases. Aust N Z J Med . 1988;18(6):799-806.

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dysfunction in subclinical hypothyroidism. J Clin Endocrinol Metab. 1997;82(10):3315-3318.

7. Weiss RE, Stein MA, Trommer B, Refetoff S. Attention-deficit hyperactivity disorder and thyroid function. J

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8. Najjar SS, Nachman HS. The Kocher-Debr’e-S’em’elaigne syndrome: hypothyroidism with muscular

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311.

Ms Ghosh is a general physician and graduate of King George's Medical University, Lucknow, Uttar Pradesh, India.

Dr Bjornsson is assistant professor of pediatrics and genetics, McKusick-Nathans Institute of Genetic Medicine and

Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland. Dr Cooke is associate

professor of pediatrics, Division of Pediatric Endocrinology, Johns Hopkins University, Baltimore. The authors have

nothing to disclose in regard to affiliations with or financial interests in any organizations that may have an interest i

any part of this article. Dr Hoover-Fong, associate professor, Greenberg Center for Skeletal Dysplasias, McKusick-

Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, is also a consultant to BioMarin. She

reports that her consultative work has no influence or connection to this article.

Hans Tomas Bjornsson, MD, PhD

David Cooke, MD

Julie Hoover-Fong, MD, PhD, FACMG

Ankita Ghosh, MBBS
http://contemporarypediatrics.modernmedicine.com/authorDetails/380614http://contemporarypediatrics.modernmedicine.com/authorDetails/380598http://contemporarypediatrics.modernmedicine.com/authorDetails/380600http://contemporarypediatrics.modernmedicine.com/authorDetails/380599http://www.uptodate.com/contents/causes-of-short-stature?source=search_result&search=causes+of+short+stature&selectedTitle=1~150

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