Pregnancy is frequently complicated by
polyhydramnios. Respiratory distress immediately after birth has been
reported in a few patients. Characteristically, patients are born with
increased birth weight and macrocephaly, which is followed by postnatal
growth retardation and failure to thrive. Patients often require an enteral
feeding tube because of oral motor apraxia and swallowing problems. This
period is called the marasmic phase, which is followed by the pseudo-thesaurismotic phase
that is characterized by a storage disease-like picture with macrocephaly,
full cheeks, large mouth with thick lips, macroglossia, and gingival
hyperplasia. The disease involves the head and neck (macrocephaly, coarse
facies, strabismus, keratoconus, chorioretinal dystrophy, hypertelorism,
epicanthal folds, downslanting palpebral fissures, low-set ears with fleshy
earlobes and helices, depressed nasal bridge with bulbous nose and
anteverted nostrils, full cheeks, micrognathia, retrognathia, large mouth
with macroglossia, high arched palate, bifid uvula, abnormal teeth, short
neck), the skeleton (short stature with adult height between 118 and 148 cm,
barrel chest, pectus excavatum/ carinatum, scoliosis, broad hands and feet,
limited extension in elbow and wrist, pes equinovarus, subluxation of hip
and elbow, osteoporosis), the skin (redundant skin on hands and feet leading
to deep palmar and plantar creases and ridges, acanthosis nigricans,
hyperkeratosis, fine hair, papillomata [facial, laryngeal, axillary,
abdominal, cubital, popliteal, anal], multiple pigmented nevi, capillary
hemangiomata on the forehead), the central nervous system (developmental
delay with an IQ between 47 and 85, speech development delay, seizures, mild
brain atrophy, cerebellar atrophy, generalized ventricular dilatation
[occasionally requiring ventriculoperitoneal shunting], muscular hypotonia
or hypertonia), and the genital region (cryptorchidism, inguinal hernia). Cardiac
abnormalities including hypertrophic cardiomyopathy, pulmonary stenosis,
atrial and ventricular septal defects, and dysrhythmias have been described.
Hepatosplenomegaly and umbilical hernias have been described in some
patients. These patients have an increased risk for malignant solid tumors
(up to 17% of patients), including neuroblastoma, rhabdomyosarcoma, and
bladder carcinoma. Laryngeal web, crumpled vocal cords, and
tracheoesophageal fistula have been described in one patient each. Abnormal
glucose metabolism occurs occasionally. A study found low levels of growth
hormone and reported good response to growth hormone therapy. Cardiac
problems, failure to thrive, and pneumonia are the main reasons for early
death.