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Genitopatellar syndrome Delineating the anomalies of female genitalia.

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American Journal of Medical Genetics 111:316 –318 (2002)
Clinical Report
Genitopatellar Syndrome: Delineating the Anomalies of
Female Genitalia
Edward J. Lammer* and Liane Abrams
Division of Medical Genetics, Children’s Hospital and Research Center, Oakland, California
We report the second female with genitopatellar syndrome, a recently identified arthrogryposis syndrome. The salient features
include severe mental retardation and microcephaly with absence of the corpus callosum, absent/hypoplastic patellae, genital
anomalies, and hydronephrosis.
ß 2002 Wiley-Liss, Inc.
KEY WORDS: genitopatellar
female genitalia; arthrogryposis; absent patellae
The genitopatellar syndrome is a newly identified
syndrome consisting of arthrogryposis with characteristic positioning of the legs and feet associated with
absent/hypoplastic patellae, severe mental and growth
retardation, agenesis of the corpus callosum, genital
hypoplasia, and hydronephrosis. We report the second
female described with this syndrome and delineate
additional features.
This female patient was initially examined as a
newborn and has been followed at the genetics clinic
until 41 months of age. She was born by urgent cesarean
section for fetal distress and footling breech presentation to a 39-year-old gravida 4 para 1-2 AB2 Caucasian
mother at 38 weeks gestation. The family history was
noncontributory and the parents were not consanguineous. The pregnancy history was remarkable for sharp,
repetitive fetal movements, vaginal bleeding in the second trimester, and fifth disease in the third trimester.
*Correspondence to: Edward J. Lammer, M.D., Division of
Medical Genetics, Children’s Hospital and Research Center, 747
52nd Street, Oakland, CA 94609. E-mail:
Received 28 March 2002; Accepted 17 April 2002
DOI 10.1002/ajmg.10582
ß 2002 Wiley-Liss, Inc.
An amniocentesis was done because of maternal age and
it showed a normal 46,XX fetal karyotype and normal
amniotic fluid alpha-fetoprotein. At delivery, meconium
staining was noted, and Apgar scores were 6 (one min)
and 9 (five min). Birth weight was 2,465 g (3rd centile),
length was 45 cm (3rd centile), and head circumference
was 30 cm (< 3rd centile). The newborn exam showed a
very small anterior fontanel, hypotonia, and flexion
contractures of the hips and knees with laterally
deviated feet and toes. A chest radiograph showed only
eleven pairs of ribs. Renal ultrasonography showed
slight prominence of the renal pelves. Head computed
tomography (CT) scan suggested a thin corpus callosum
and brain magnetic resonance imaging (MRI) at
12 months confirmed this.
Her legs were casted for months trying to treat the
bilateral valgus feet positioning and knee flexion contractures, with some success. She required gavage feedings throughout the first year, and at 16 months, a
feeding gastrostomy tube was placed; this has been her
only source of nutrition since that time. In later infancy,
she developed gastroesophageal reflux and tracheomalacia. Her motor and language development were significantly delayed, as well as tooth eruption (at 18 months
only two mandibular central incisors had erupted). Eye
exams showed cortical visual impairment with normal
appearing optic nerves and retinas. Plasma amino acids,
urine organic acids, urinalysis, thyroid hormone, and
thyroid stimulating hormone (TSH) were normal.
Echocardiogram revealed a large secundum atrial septal
defect. Additional workup included fluorescence in situ
hybridization (FISH) for 4p and 5p microdeletions and
transferrin sialylation analysis to rule out carbohydrate-deficient glycoprotein syndrome, all of which were
normal. Patellae were not palpable and radiographs of
the knees at 39 months showed no patellar ossification.
A brain MRI was repeated at 39 months and showed a
small corpus callosum with absent genu, marked narrowing of the midbody, and a small splenium.
She was most recently examined at 40 months. Her
height was 89 cm (< 3rd centile), weight was 14 kg (5–
10th centile), and head circumference was 42.5 cm
(< 3rd centile). Cranial shape was normal except for
bitemporal flattening. Scalp hair was thin and decreased
in density and her mother reported rarely trimming it.
Genitopatellar Syndrome
Fig. 1. Craniofacial features at 40 months show sparse scalp hair,
temporal flattening, prominent nasal bridge with hypertelorism, and open
Orbits were shallow and she had hypertelorism (interpupillary distance 56 mm) and the nasal bridge was
prominent (Fig. 1). Intraorally, she had lateral palatine
hypertrophy, but many teeth were now erupted and they
appeared normal. She had inverted nipples. There was a
prominent suprapubic fat pad and the external genitalia
were abnormal, with a small clitoris, hypoplastic labia
minora, and anterior displacement of the anus (Fig. 2).
Elbows and wrists were hyperextendable. Hips and
knees were flexed and feet were in valgus position relative to lower legs. There were severe knee contractures
and the patellae were not palpable. The second toes
Fig. 2. External genitalia show a very prominent suprapubic fat pad,
small clitoris, and underdeveloped labia, especially labia minora.
Fig. 3. Feet positioning. Both feet were held in a valgus orientation to
the lower legs. Note valgus deviation of left toes with overlapping by great
and second toes.
overlapped the third and the great toes overlapped the
second (Fig. 3). Her neuromuscular tone was mixed,
with hypertonia of the trunk and hypotonia of the extremities; deep tendon reflexes were decreased but symmetric. She occasionally grasped for objects but visually
tracked inconsistently. She had severe developmental
retardation, babbled occasionally but had no expressive
language, and had no apparent language comprehension. It was unclear whether she recognized family members. She had severe gross motor delays with limited
mobility (could sit and rock on hands and knees).
We diagnosed genitopatellar syndrome on the basis of
congenital flexion contractures of the hips and knees,
severe motor and language delays, hypoplastic/dislocated patellae, and abnormal female external genitalia.
The positioning of the legs (flexion contractures at the
hips and knees, with the feet hyperflexed and varus)
seems like it might be a characteristic position for this
syndrome, but this appearance of the legs is more likely
nonspecific and it may be characteristic of a number of
conditions with absent/hypoplastic patellae. Seven infants with this syndrome have been described and it has
been characterized in only one female [Goldblatt et al.,
1988; Cormier-Daire et al., 2000; Reardon, 2002]. The
abnormalities of the genitalia are more obvious in males
(cryptorchidism, underdeveloped scrotum), aiding the
diagnosis of this syndrome, but the abnormalities may
be more difficult to appreciate in females. Cormier-Daire
et al. [2000] described clitoral hypertrophy and prominent labia minora in the female in their report. In
contrast, our patient had a small clitoris and underdeveloped labia minora. The anus was anteriorly displaced so
that there was only a narrow wedge of perineum. We also
observed these additional findings that have not been
previously reported in genitopatellar syndrome: atrial
septal defect, sparse thin scalp hair, inverted nipples, and
delayed eruption of primary teeth. In contrast to the cases
Lammer and Abrams
described by Cormier-Daire et al. [2000], but like the child
described by Reardon [2002], we did not feel that our
patient had coarse facies. Absence or hypoplasia of the
corpus callosum has been found in most children with
genitopatellar syndrome, but other brain anomalies have
not been identified, despite the severity of developmental
retardation and microcephaly. Recurrences among two
of the families reported by Cormier-Daire et al. [2000]
suggests that the inheritance pattern of genitopatellar
syndrome is likely autosomal recessive.
Cormier-Daire V, Chauvier M-L, Lyonnet S, Briard M-L, Munnich A,
Le Merrer M. 2000. Genitopatellar syndrome: a new condition comprising absent patellae, scrotal hypoplasia, renal anomalies,
facial dysmorphism, and mental retardation. J Med Genet 37:520–
Goldblatt J, Wallis C, Zieff S. 1988. A syndrome of hypoplastic patellae,
mental retardation, skeletal and genitourinary anomalies with normal
chromosomes. Dysmorphol Clin Genet 2:91–93.
Reardon W. 2002. Genitopatellar syndrome—a recognizable phenotype. Am
J Med Genet.
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anomalies, genitopatellar, syndrome, genitalia, delineation, female
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