Solitary median maxillary central incisor with congenital strabismus and autoimmune thyroiditis in a young child

Abstract

Single median maxillary central incisor (SMMCI) syndrome is rare. It is commonly associated with other midline defects. About 50% of children with SMMCI have short stature, associated with isolated growth hormone deficiency or panhypopituitarism.

A 6-year-old girl presented to us with worsening convergent squint, slowing linear growth and a suspected pituitary macroadenoma on neuroimaging. The key findings on examination included a disproportionate short stature, SMMCI, congenital abduction defect and pseudohypertrophy of calf muscles with myopathy. The evaluation showed autoimmune thyroiditis with pituitary hyperplasia. Bone age corresponded to 3 years.

Three months after initiation of thyroxine, her myopathy resolved, and the hormone profile and neuroimaging were normal. Autoimmune thyroiditis in association with SMMCI is not reported previously. This case study emphasises the importance of growth monitoring and the exclusion of common treatable conditions.

Background

Single median maxillary central incisor (SMMCI) syndrome (OMIM 147250) refers to single upper midline central incisor of deciduous and permanent dentition. It is rare, reported in 1:50 000 live births.¹ SMMCI occurs isolated or syndromic with other anomalies.^1–4 It is considered the microform of holoprosencephaly and occurs as a triad with microcephaly and hypotelorism.^{2 5} About 50% of children with SMMCI have short stature, associated with isolated growth hormone deficiency or panhypopituitarism.1 4 6 7

We report a young child with SMMCI and autoimmune thyroiditis, not until now described in the literature. The clinical presentation and neuroimaging masqueraded a brain tumour.

Case presentation

A 6-year-old girl presented to us for a suspected brain tumour on neuroimaging. Parents' concerns included worsening convergent squint in the left eye and slowing linear growth since 4 years of age. The child reported a dull headache for the last 3 months, and parents also noted a smaller left eye. She suffered from muscle fatigue and cramps in her lower limbs and refused to walk. A history of visual disturbances, vomiting, motor weakness or gait abnormality was not forthcoming. She was born preterm with a birth weight of 2835 g to nonconsanguineous parentage. Her mother was on thyroxine for autoimmune thyroiditis, diagnosed at the age of 13 years. She had no dysmorphic features. Her height was between 0 and −2 SD.

On examination, the child was interactive. Her weight was 15.2 kg (between 0 and −2 SD), height was 96 cm (< −3 SD), and head circumference was 47 cm (between −2 and −3 SD). Her height corresponded to a 3.5 year old with disproportionate segmental ratio. The projected height was below −3 SD for the mid parental height. There was a single upper central incisor with a broad root with no labial frenulum (figure 1). Limited abduction of the left eye with a small left eye suggested Duane retraction syndrome type 1. She had no other facial dysmorphism. There was no thyroid swelling. She had a bilateral calf and thigh muscle hypertrophy, hypotonia, diminished power in proximal muscles, brisk deep tendon reflexes and slow returns. Cardiac examination was normal.

Figure 1.

Single upper maxillary central incisor of primary dentition.

Investigations

MRI of the brain showed pituitary hyperplasia with a widening of the sella tursica reported as macroadenoma (figure 2). The pituitary showed diffuse contrast enhancement. The pituitary stalk contour and the position of the posterior pituitary bright spot were normal. Further evaluation showed elevated serum thyroid-stimulating hormone (1764.5 μIU/mL (reference 0.4–5.0)), decreased free thyroxine (0.67 pmol/L (ref: 10–20)), elevated creatine phosphokinase (552.0 IU/L (reference <250)) and normal serum cortisol (365.3 nmol/L (reference 138–635)). Haemogram, renal and liver function tests were normal. X-ray wrist showed two carpal bones (capitate and hamate) with epiphysis at the lower end of the first metacarpal bone. The estimated bone age was 3 years (figure 3). Thyroid peroxidase antibody was positive (92.0 IU/mL (reference <34). Radionuclide technetium scan showed normally placed thyroid gland with high uptake of the isotope. Her echocardiogram and abdominal sonogram were normal. Audiometry evaluation of hearing was normal.

Figure 2.

MRI of the brain (T1 weighted) shows enlarged sella tursica, pituitary hyperplasia, normal contour pituitary stalk and the posterior pituitary bright spot (sagittal) with contrast enhancement (coronal).

Figure 3.

X-ray wrist anterior–posterior view for bone age. Epiphysis at the lower end of the first metacarpal suggests a bone age of 3 years.

Differential diagnosis

The clinical and lab parameters suggested autoimmune thyroiditis with pseudo muscular hypertrophy and myopathy. Duane eye retraction syndrome and SMMCI were associated features.

Treatment

Levothyroxine was started at 50 μg and subsequently titrated to 87.5 μg in the follow-up based on lab parameters. Furthermore, she was advised ocular exercises and dental care.

Outcome and follow-up

Three months after initiation of thyroxine, the lab values, serum thyroid-stimulating hormone (11.12 μIU/mL), free thyroxine (1.39 pmol/L), creatine phosphokinase (85 IU/L), returned to baseline. Serum insulin-like growth factor was normal. Brain imaging showed resolution of pituitary hyperplasia with a slight deviation of the pituitary stalk (figure 4). A catchup height velocity was seen in the 2-year follow-up of the child. Figure 5 depicts the follow-up dental X-rays. A combined orthodontic and prosthodontic aesthetic dental treatment is planned after her permanent dentition is completed.

Figure 4.

MRI of the brain (T1 weighted) shows widened sella tursica, normal pituitary tissue with posterior pituitary bright spot and a deviated pituitary stalk (arrows—sagittal and coronal views).

Figure 5.

Periapical and panoramic dental radiographs showing permanent single upper maxillary central incisor.

Discussion

Rappaport et al⁸ in 1976 first described SMMCI in seven unrelated patients. It is a midline defect hypothesised to be resulting from a developmental field defect occurring around day 35–38 of conception.¹ Poelmans et al report phenotypic and genotypic variability in six unrelated children with SMMCI.² Neuroimaging was normal in all.

Features previously described in SMMCI and seen in the index case included short stature and Duane retraction syndrome. Parentin and Perissutto report a 4 year old with SMMCI, Duane retraction syndrome, growth hormone deficiency and a thumb anomaly. Neuroimaging showed a hypoplastic pituitary with empty sella.⁹ Other authors also describe convergent squint.^{2 7}

Duane retraction syndrome is a congenital eye movement anomaly characterised by limited horizontal gaze, with narrowing of palpebral fissure and globe retraction on attempted medial movement.¹⁰ The syndrome results from an insult to the sixth nerve nucleus or nerve at 4–8 weeks of gestation.¹¹

SMMCI and short stature due to primary hypothyroidism or autoimmune thyroiditis are not reported in the literature. Elevated thyroid-stimulating hormone and pituitary hyperplasia in neuroimaging suggested primary hypothyroidism. We considered a late-onset congenital hypothyroidism due to partial dysgenesis of the thyroid gland as the aetiology, until we received the thyroid peroxidase antibody level.

Autoimmune thyroiditis is common among girls and peaks around puberty. It is rare below 6 years of age, and to our knowledge, the lowest reported age is 3 years and 8 months.¹² Pituitary hyperplasia and myopathy suggested a long-standing disease, and the height age and bone age corresponded to onset around 3 years of age.

The pseudohypertrophy and myopathy seen in untreated hypothyroidism are described variably as Kocher-Debré-Sémélaigne in children or Hoffman syndrome in adults.¹³ Kocher-Debré-Sémélaigne syndrome is reported with both congenital and acquired forms of hypothyroidism and responds to thyroxine replacement. The proposed mechanisms include altered cellular metabolism due to thyroxine deficiency, muscle necrosis, glycosaminoglycan and fat depositions, all resulting in elevated serum creatine phosphokinase. The worsening squint due to ocular myopathy prompted the referral as a brain tumour.

Learning points.

• This report emphasises the importance of growth monitoring in children and the exclusion of common treatable conditions by the primary physician.

• Autoimmune thyroiditis can occur in young children.

• Presence of rare congenital disabilities like single median maxillary central incisor and Duane eye retraction syndrome as in this child can influence the clinical approach.