Prenatal phenotype of 48, XXYY with elevated MSAFP

Abstract

Elevated maternal serum alpha-fetoprotein (MSAFP) has long been associated with fetal abnormalities such as open neural tube defects, ventral wall defects, and cystic hygromas. The need for amniocentesis following a normal ultrasound has been debated because variability in ultrasound quality is vast. From several studies the incidence of fetal aneuploidy ranges from 0.6-1%, the incidence of all chromosomal abnormalities in women age 36 undergoing amniocentesis. We believe that providers should offer amniocentesis to women who have elevated MSAFP and a normal ultrasound since the quality of ultrasound varies widely.

SD a G₂ P₁₀₀₁, 32 year old Guyanese female, was seen for genetic counseling and amniocentesis at 19 weeks for elevated MSAFP (3.19MoM). Ultrasound performed a few days prior did not note any fetal abnormalities. Family history revealed the patient's brother had isolated polydactyly, a common malformation. She declined the procedure because of the risk of a miscarriage. An anatomic exam at 21 weeks revealed bilateral clubfeet and possible left-hand postaxial polydactyly. The patient declined amniocentesis again and missed an appointment for fetal echocardiography.

The baby was born premature, at 29 weeks gestation by cesarian section. This was the second child born to these non-consanguineous parents. Birth weight was 1155 gms (25^th%ile), length 37.5 cm (25^th-50^th%ile), and head circumference was 27.5 cm (50^th - 75^th%ile). Physical exam revealed minimal facial dysmorphic features including: hypertrichosis-especially of the forehead, relatively small eyes, lowset ears with malformed pinnae, and a prominent nasal bridge. Other notable findings included: normal male genitalia (with slight chordee), sacral dimple, long slender fingers, prominent convex nails and bilateral clubfeet (equinus varus). Chromosomal testing revealed a 48 XXYY karyotype, which may have originated from consecutive meiotic non-dysjunction during paternal gametogenesis.