Defining manifestations . . .
In making the determination, a geneticist will look for the presence of the
three defining manifestations of the syndrome: pre- and/or postnatal growth
retardation, primary microcephaly, and the characteristic facial appearance.
1. Pre and postnatal growth retardation:
Children with Dubowitz syndrome nearly always have a history of intrauterine
growth retardation involving both low birth weight and reduced length. In their
1996 review of 141 cases, Tsukahara and Opitz [11] place the average birth weight
of males at 2413 g (approximately 5 lb. 4 oz.) with a range of 900-3600 g, and
the average birth weight of females at 2221 g (approximately 4 lb. 14 oz.) with
a range of 1300-3500 g. The authors report that growth retardation usually
persists after birth, and that typically patients born with normal weight develop
severe postnatal growth retardation over time. In cases where length is normal
at birth, a gradual fall-off in height usually occurs. Rare cases have occurred
in which growth retardation was present at birth but catch-up growth later took
place. Also noted are two exceptional cases in which neither pre- nor postnatal
growth retardation were present.
Although children with Dubowitz syndrome nearly always have short stature,
their bodies are normally proportioned.
2. Primary microcephaly:
Microcephaly is generally defined by geneticists as a "head circumference
(measured snugly around the widest part of the head above the ears and just
above the eyebrows) of 2 or more standard deviations (2 SD) below the mean."
The mean is at the 50% line on the chart of observed head circumference sizes
for children of a given age, and 2 SD below the mean falls approximately at
the 2% line. There are separate charts for boys and girls, and the chart
selected should be adjusted for prematurity or postmaturity at birth. The
child's body size and the parents' head circumferences should be taken into
consideration as well.
Primary microcephaly describes "small head size that is present at birth"
--in contrast to secondary microcephaly, which is "microcephaly developing later
in a child whose head circumference was normal at birth." Dubowitz syndrome is a
condition of primary microcephaly, the degree of which is usually mild and
sometimes in the borderline range. Microcephaly is present in virtually
every patient with the syndrome (three exceptions, however, have been
reported, see Lyonnet et al. 1992 [32], Levin et al. 1987 [22] and Paradisi
et al. 1994 [18]). Based on data from 141 cases, Tsukahara and Opitz 1996 [11]
determined that the average head circumference at birth is 31.0 cm.
and the average pregnancy is 38 weeks.
Shuper et al. (1986) [26] report a case in which a child having Dubowitz
syndrome exhibited primary microcephaly but later experienced catch-up
head growth (going from the 3% to the 25% line). The authors point out
that "birth measurements are of great help in establishing the diagnosis,
as in later months they may change to normal."
3. Characteristic facial appearance:
The characteristic facial appearance has been described in nearly fifty
medical journal articles over the past thirty years, and descriptions of new
patients continue to confirm the relevance of the observations reported
in the early literature.
The facial appearance is considered the most diagnostic manifestation
of the syndrome. Grosse, Gorlin and Opitz (1971) [53] comment that
the appearance of the first four known patients was "so strikingly similar
that we would feel reasonably confident in making this diagnosis in a
sporadic case with this appearance, intrauterine growth retardation and
microcephaly. . . ." Majewski et al. 1975 [51] remark in their review of
11 patients, "The face is strikingly similar in all patients. . . ."
Fryns et al. 1979 [7] describe the syndrome as one "in which the craniofacial
appearance is the most evocative clinical indication for diagnosis." Winter
(1986) [33] writes, "The facial abnormalities make up a recognizable
gestalt. . . ." Kondo et al. (1987) [19] remark, "The most characteristic
feature of this syndrome is the marked similarity of the facial appearance. . . ."
In their 1996 review of 141 cases, Tsukarhara and Opitz [11] write, "Facial
anomalies are perhaps the most diagnostic of all physical signs."
The facial anomalies are usually mild, and the overall appearance can
be described as unusual. The characteristic facial appearance is composed
of the following features (a child need not demonstrate each and every
feature for the diagnosis to be made):
- The face is strikingly small; however, it is in proportion to the
small head. The shape of the face is often triangular.
- The chin is small (micrognathia) and usually receding (retrognathia)
as well. It is often somewhat pointed.
- The nasal bridge is broad and sometimes appears flat. There may be
bony bumps or knots at the sides of the nasal bridge. As the child
matures, the nasal bridge appears less wide and often becomes
prominent producing a continuous line with the forehead when
viewed in profile.
- Tip of nose is frequently wide, rounded, or prominent.
- There is an increased distance between the inner points of the eyes
(telecanthus).
- The interpupillary distance is increased (hypertelorism) as determined
by the distance between the pupils of the eyes.
- Patients frequently have a decreased distance between the top and
bottom eyelids when measured vertically (blepharophimosis).
- The palpebral fissures are shortened, i.e., the opening of the eyelid
is short when measured horizontally from corner to corner. Very often,
the palpebral fissures are somewhat slanted (either upward or downward).
- Vertical folds of skin on the inner side of the eyes (epicanthal folds)
are often present and cover the inner corners of the eyes (canthi),
similar to the normal variation seen in people of Asian descent.
- Drooping of the upper eyelids (ptosis) is present and is sometimes
asymmetric.
- There is underdevelopment of the facial bones in the area above
and to the sides of the eyes (hypoplastic or flat supraorbital ridges),
resulting in an unusually smooth contour across the forehead and in
the temple area.
- The forehead is usually sloping and often high.
- The forehead often appears broad, especially in young children, due
to the combination of characteristic scantiness of hair and smooth
facial contour in the temple area.
- The outer eyebrows are often scanty or absent.
- Abnormalities of the ears (involving placement, size, or form) are
usually present, ranging in degree from slight to severe.
