[source]
pmid = PMID:29483676
title = The second point mutation in PREPL: a case report and literature review
[diagnosis]
disease_id = OMIM:616224
disease_label = Myasthenic syndrome, congenital, 22
[text]
The proband is a 10-year-old female born to healthy parents as an only child (Fig. 1).
Her nonconsanguineous parents originated from the same small part of Chiloé Island off the coast of southern Chile.
She was born after an uneventful pregnancy at 38 weeks of gestation with Apgar scores of 9 and 10 at 1 and 5 min, respectively.
At birth, her weight, length, and occipitofrontal circumference were 2950 g (−0.73 SD), 49 cm (−0.33 SD), and 34 cm (−0.41 SD),
respectively. Dysmorphic features were noted at birth, including dolichocephaly, prominent ears,
long palpebral fissures with palpebral ptosis, and high-arched palate. She presented with neonatal hypotonia and feeding problems
with severe failure to thrive during the first 3 years of life (Fig. 1), requiring nutritional supplements and a nasogastric tube.
Neurological evaluation at 10 months of age revealed global hypotonia, muscle weakness, and nystagmus, which is currently absent.
After the first year of life, hypotonia and muscular weakness showed spontaneous improvement. She showed predominantly motor
developmental delay, walking independently at 27 months of age. After 1 year of age, she spoke single words with difficulty and
a remarkable nasal voice.
Serum creatine kinase was normal in her medical records. Electromyography and nerve conduction velocity were normal
at 3 and 6 years of age. Muscle biopsy had not been performed. Brain magnetic resonance imaging at 6 years was unremarkable
and serum amino-acid profile was normal. At 7 years, her intelligence quotient was 49, requiring special educational support.
At 9 years, serum insulin-like growth factor-1 (IGF-1; 199 ng/ml, normal range: 175–445 ng/ml) and IGF-binding protein-3
(IGFBP-3; 3188 ng/ml, normal range: 3100–4544 ng/ml) were normal, and bone age was concordant with her chronological age.
Growth hormone and sexual hormones were not measured. Her karyotype is 46,XX.
From the age of 4 years, she developed hyperphagia (Fig. 1). Her current body mass index at 10 years is 27.6 kg/m2 (+2.8 SD)
based on weight (46 kg, +1.9 SD) and height (129 cm, −1.6 SD). She had facial weakness with bilateral palpebral ptosis,
open mouth with tented upper lip, and large front teeth (Fig. 1). Social development is normal. Salivation is normal,
and her nasal voice persists. Her motor exam revealed that the patient has global muscle weakness and it is more
prominent at the proximal muscles (deltoid and psoas muscles), with reduced osteotendinous reflexes and Gower sign.
Her gait is normal and mild scoliosis is recognized, and she is accordingly receiving physiotherapeutic intervention.
There is no history of fatigability or muscle wasting induced by exercise or fluctuation in peripheral weakness.
Facial weakness is occasionally seen and irregularly improves transiently together with mild attenuation of palpebral ptosis
and open mouth.