[source]
pmid = PMID:28687524
title = Pierpont syndrome associated with the p.Tyr446Cys missense mutation in TBL1XR1
[diagnosis]
disease_id = OMIM:602342
disease_label = Pierpont syndrome
[text]
Both parents were healthy and of Caucasian ethnicity without
known consanguinity. A maternal uncle was diagnosed incidentally
with an Arnold-Chiari malformation, but additional medical
records were not available. The pregnancy with the proband was
complicated by hypertension and hyperemesis, but no maternal
exposures were reported. An ultrasound scan at 34 weeks of
gestation showed reduced fetal movements without any detected
structural abnormalities, and an ultrasound scan at 35 weeks was
reported to be normal. The proband was born to a 28-year old,
G1P0-1 mother by spontaneous vaginal delivery at 40 weeks and 6
days of gestation. His weight was 3286 g (10e25th centile) and
length was 50.8 cm (25-50th centile). Apgar scores were 3, 4, and
8 at 1, 5 and 10 min respectively. He remained in the neonatal
intensive care unit (NICU) for 25 days after birth because of
respiratory distress and jaundice and was evaluated for sepsis during
his stay.
During the neonatal period, he was noted to have dysmorphic
features and global developmental delays. A submucous cleft palate
was identified at three years of age, but no surgery was performed
and he suffered episodes of food in his Eustachian tubes.
His general health was complicated by frequent ear infections that were
treated by myringotomy at five years of age and he had a perforated
right tympanic membrane. However, his last audiogram at five
years of age showed normal hearing. He has had chronic constipation and had one admission for fecal impaction. He underwent
surgery for strabismus and had orchidopexy for bilateral cryptorchidism at five years of age. He has been treated for talipes with
braces. When last seen at seven years of age, he had oral aversion,
and his diet was limited to avocado, rice cereal and flaxseed oil. He
was able to crawl and walk independently. He was able to babble
and vocalize but did not utter words with meaning; he would tug
on his parents’ clothing and use a picture board to communicate his
needs.
On examination at seven years of age, height was 111.8 cm
(0.21st centile; Z score 2.86) and weight was 18.5 kg (0.46th
centile; Z score 2.6). Head circumference was 49.5 cm at five years
of age (19th centile). He had a frontal upsweep with a high anterior
hairline, small eyes with slightly upslanted and narrow palpebral 
fissures and relatively large ears. The nasal tip was bulbous and he
had a short columella and a large mouth with a thin vermilion and a
small chin. The left side of his chest was prominent and he had
thoracolumbar scoliosis. The elbows could not fully extend and he
wore orthoses for bilateral talipes. He had camptodactyly of the
second to fifth fingers and short second and fifth toes and his
second toes overlapped his third toes bilaterally. His fingers were
doughy and his hands and feet showed fleshy palmar and plantar
skin with deep creases. There was lateral foot dimpling at the fifth
metatarsophalangeal joints. His hands and feet were reddened, and
he had small nails. He was hypotonic and the reflexes were hard to
elicit.
A magnetic resonance imaging (MRI) scan of the brain showed
an Arnold-Chiari malformation type I, with crowding of the foramen magnum.
An abdominal radiograph showed a 3.2  3.4 cm
cystic structure in the left perihilar region that was thought to be a
bronchogenic cyst. Radiographs of the pelvis and spine showed a
large, S-shaped right thoracic scoliosis with an apex at T8 and a
40 curvature, a left thoracolumbar scoliosis with the center at L2
and a 47 curvature. His chest was described as ‘bell-shaped’ and
his pelvis had large iliac crests and a small inlet. Renal imaging
showed hydronephrosis, multiple bilateral renal cysts and calyceal
diverticula.