Contributed by Marie Dvorakova, MD and K. Michael Gibson, PhD, FACMG
Published on line in January 2007
These 5-month-old female twins were referred to a Genetic Counselor shortly after birth for developmental delay and dysmorphic features.
The girls were born to a 29-year-old G3P2 mother after an uneventful pregnancy at 38 weeks' gestation by a normal spontaneous vaginal delivery. Birth weights were 2300 g and 2500 g. At birth, both girls were found to have a similar set of dysmorphic features, particularly abnormal head shape along with large anterior and posterior fontanelle. Both girls failed the newborn hearing screen initially but passed two weeks later. Early postnatal course was complicated by poor feeding, failure to thrive and liver failure with significant coagulopathy.
Physical examination at 5 months revealed proportionate-looking infants with generalized hypotonia and dysmorphic features (macrocephaly with frontal bossing and significantly prominent vessels, large anterior fontanelle, blue-gray sclereae, mid-face hypoplasia, narrow palate, micrognathia, low set ears, bilateral simian creases). Hepatosplenomegaly was also noted. Height and weight were both at 3rd percentile. Developmental milestones provided by the parents were suggestive of global developmental delay: no social smile on stimulation or cooing was observed.
Family history: Positive for strabismus and a unilateral simian crease in the 3-year-old brother, as well as for severe myopia in the father; otherwise non-contributory.
Chromosomal analysis: 46, XY
Comparative Genomic Hybridization: negative for microdeletion/duplication entities
Methylation analysis of the SNRPN locus (Prader-Willi/Angelman Syndrome): normal biparental inheritance
CT of the head: unremarkable
Ophthalmologic exam: no retinal abnormalities
Skeletal survey: no abnormalities, normal bone age
Biochemical tests: plasma amino acids, 7-dehydrocholestrol and urine for quantitative organic acid and N-acetylaspartic acid within normal limits; transferrin isoelectric focusing: no congenital defects of glycosylation
Plasma Very Long Chain Fatty Acids by GS/MS:
15.89 - 37.41
11.12 - 28.96
0.19 - 0.35
0.63 - 0.87
0.00 - 0.02
Phytanic acid (µg/ml)