Robinow Syndrome: An Update - GGH Journal

Meinhard Robinow, MD
Clinical Professor of Pediatrics
Emeritus
Wright State University School of
Medicine
Dayton, Ohio
In 1969, Silverman, Smith, and I
reported a family consisting of 3
siblings, mother, and grandmother
with "a previously unrecognized
dwarfing syndrome."1 The major
features were: moderately short stature,
characteristic facial dysmorphism,
genital hypoplasia, and
mesomelic brachymelia. The facial
characteristics (Fig 1) included
hypertelorism; short, upturned nose;
long philtrum; broad, triangular
mouth; and dental malalignment
(Fig 2). The genital hypoplasia consisted
of micropenis in the males
(Fig 3) and hypoplastic clitoris and
labia minora in the females. Somewhat
later, I proposed the more
descriptive term "fetal face syndrome,"
since the face resembles
that of the human fetus at 8 weeks2
(Fig 4).
In 1973, Wadlington et al3 published
4 more cases of the syndrome
and added vertebral segmentation
anomalies to the clinical spectrum.
In the more than 30 publications on
the syndrome,4 a number of other,
less constant anomalies have been
described, some nonspecific, others
more nearly unique and thus of
greater diagnostic value (Table).
In most cases, the diagnosis is
obvious on inspection. In "atypical"
cases, when some of the major features
are missing, the diagnosis
must remain in doubt. Atypical
cases have not been reported in
relatives of "classic" cases.
Genetics
In the index family,1 transmission of
the syndrome was autosomal dominant.
Two of the patients of Wadlington
et al,3 boy-girl siblings, were
children of normal parents, strongly
suggesting autosomal recessive
inheritance. Since then, both modes
of inheritance have been amply
documented. As to be expected,
pedigrees indicating recessive
inheritance have been encountered
more often in populations with high
rates of consanguinity, eg, Arabs.
I believe characteristic dominant
and recessive phenotypes can be
delineated. 5 Individuals with the
dominant form seem to have normal
stature or only mild dwarfing, no vertebral
abnormalities or, at most, a
single butterfly vertebra, and only
mild forearm brachymelia. Patients
with the recessive form seem to have
more severe dwarfing, more extensive
vertebral segmentation defects,
and more severe forearm brachymelia
and dysplasia (Fig 5). Intrafamilial
variability has been slight
while interfamilial variability has been
considerable, so that further genetic
heterogeneity seems likely.
Unfortunately, all the diagnostic
criteria for this syndrome are morphologic.
No metabolic defect has
been identified; no animal model is
known. Chromosome studies have
yielded uniformly normal results,
although chromosome mapping
has not been attempted.
Teratogenic Period
Since the face and the external
genitalia attain their final shape at
around 10 weeks of gestation, some
authors have speculated that this
may also be the teratogenic period
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The Future
Further studies of the phenotype are
not likely to add much to present
understanding. Progress will have to
await metabolic and molecular genetic
studies. Once the gene abnormality(ies)
has (have) been identified,
we can derive a better classification
and may gain a better insight not
only into the teratogenesis of the
syndrome but also into mechanisms
of normal embryogenesis.
References
1. Robinow M, Silverman FN, Smith HD.
Am J Dis Child 1969;117:645-651.
2. Patten MB. Human Embryo/og}( 3rd ed.
New York, NY: Blakiston; 1968:346.
3. Wadlington WB, Tucker VL, Schimke
RM. Am J Dis Child 1973;126:202-205.
4. Butler MG, Wadlington MB. Robinow
syndrome: report of two patients and
review of the literature. Clin Genet 1987;
31:77-85.
5. Robinow M, Markert RJ. Proceed
Greenwood Genet Center 1988;7:144.
6. Lee PA, Migeon CJ, Brown TR,
Robinow M. Am J Dis Child 1982;
136:327-330.
for the syndrome. However, vertebral
segmentation is normally completed
at 4 weeks, suggesting that teratogenesis
is more extended, at least in
the recessive type.
Course
Approximately 10% of patients have
died in infancy, most of them of pulmonary
disease or cardiac malformations.
Probably all the deaths
occurred in the recessive type. The
remaining 90% seem to have
enjoyed good health. The facial features
become less striking at puber-ty,
which may explain the fact that
almost all index cases have been in
infants and young children.
Endocrine Aspects
Sexual maturation occurs at the
usual age in both sexes. In males,
the penis remains abnormally short
but may attain normal circumference,
permitting sexual function.
Endocrine studies by Lee et al6
suggested partial primary hypogonadism.
Androgen receptors and
Sa-reductase in genital skin fibroblasts
were normal. Females with
both the dominant and recessive
forms have reproduced, as have
males with the dominant type. Reproduction
by males with the recessive
form has not yet been documented.
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