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Transcript
rd
Genetics in the 3 millennium, Vol. 4, No. 4, Winter 2006
Case Report
Aarskog-Scott syndrome:Report of 7 cases and review of literature
Bita Bozorgmehr*, Ariana Kariminejad, Valeh Hadavi
Mohammad Hassan Kariminejad
Kariminejad, Kariminejad -Najmabadi Pathology and Genetics Center, Tehran, Iran
Abstract
Aarskog-Scott syndrome (ASS) is an X-linked disorder, characterized by facial, skeletal and genital
anomalies. It is also known as faciogenital dysplasia (FGDY, OMIM No. 305400) and facio-digito-genital
syndrome. The main features are short stature, hypertelorism, short hands and feet, and shawl scrotum.
We are reporting 7 cases with this syndrome that were referred to our genetic center from 1995 to 2006
for clinical genetic counseling and cytogenetic study.
Key words: Aarskog-Scott syndrome; Genes, X-linked
Introductoin
Faciogenital dysplasia, (FGDY, OMIM No.
305400) or Aarskog-Scott syndrome (ASS) was
first described, separately by Aarskog and Scott
at the third conference (1970) on the clinical
delineation of birth defects, in two different
families with multiple affected males (1,2). The
syndrome is an X-linked disorder characterized
by short stature, craniofacial dysmorphism
(hypertelorism, down slanting palpebral fissures),
short hands and feet and urogenital abnormalities
(3). Birth size is usually normal and growth
retardation does not become evident until the
* Bita Bozorgmehr,MD
1143 Med Bldg, Sanat Sq, Shahrak Ghods. PO box 14665/154 Tehran/Iran
954
age of two to five. Most patients are below the
third percentile in height, adults rarely exceeding
the third percentile. The facies is especially
characteristic. The forehead is broad, often with
a widow's peak and prominent metopic ridge.
They have round face, hypertelorism, downslanting palpebral fissure, mild ptosis of one or
both eyelids, short broad and somewhat stubby
nose with anteverted nostrils. The philtrum is
long and the midface somewhat flattened.
Frequently, there is a broad upper lip with a linear
dimple below the lower lip. The earlobes are
often thick, with malformed upper helices. The
hands are short and wide with hypermobile
fingers and hyperextensibility of the proximal
Bita Bozorgmehr, Ariana Kariminejad, Valeh Hadavi, et al.
Table 1. Summary of clinical findings of 7 cases with Aarskog-Scott syndrome.
Age
Short Stature
Round facies
Hypertelorism
Ptosis
Down-slanting
palpebral fissures
Small nose
Broad philtrum
Maxillary hypoplasia
Hypodontia
Short hands
Clinodactyly of the
th
5 finger
Interdigital Webbing
Pectus excavatum
Shawl scrotum
Mental retardation
Case 1
Case 2
Case 3
Case 4
Case 5
Case 6
Case 7
Total
6y
+
+
+
–
+
2y
–
+
+
+
+
5y
+
+
+
+
+
12 y
+
+
+
+
+
6m
–
+
+
+
+
6y
+
+
+
+
+
6y
–
+
+
–
+
4/7
7/7
7/7
5/7
7/7
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
–
–
–
+
+
–
–
–
–
+
+
–
+
+
+
+
+
–
–
–
–
+
+
+
+
+
+
7/7
7/7
4/7
4/7
4/7
4/7
+
+
+
+
+
+
+
+
–
–
–
+
–
–
–
+
–
–
–
+
–
+
+
+
–
+
+
+
2/7
4/7
4/7
7/7
interphalangeal joints and mild flexion deformity
at the distal interphalangeal joints. Clinodactyly
of fifth fingers is also seen. There may be mild
cutaneous syndactyly.
Bilateral simian creases and a single crease in
the fifth fingers are frequent. The feet are broad,
with bulbous toes. The joints in the hands, knees,
and feet are lax. The external genital anomalies
are striking; the scrotal fold extends ventrally
around the base of the penis, causing the scrotum
to appear bifid, somewhat resembling a shawl
thrown around the neck; hence termed "shawl
scrotum".
There are often unilateral or bilateral
cryptorchidism and inguinal hernia. There are
various orthopedic problems, including mild
cubitus valgus, internal tibial torsion, metatarsus
varus, pes planus, pectus excavatum, and
hypermobility of interphalangeal joints. Bone
age is retracted. Puberty is often delayed and
adult height rarely exceeds 160 cm.
.
Hypodontia, retarded dental eruption, broad
central upper incisors (permanent dentition),
orthodontic problems and some degree of
maxillary hypoplasia have been seen (3).
Mild to moderate mental deficiency is relatively
frequent. Hyperactivity and attention deficit
disorders are common, particularly in the mentally
subnormal patients (4).
Aarskog-Scott Syndrome is an X-linked
condition. It is caused by mutation of the FGD1
gene mapped to the X p11.21 region (5).
FGDY1 appears to code for a Rho/Rac guanine
nucleotide exchange factor, a class of proteins
involved in growth regulation and signal
transduction, suggesting a mechanism through
which the growth anomalies seen in the AarskogScott Syndrome are produced (3).
Case report
Summary of clinical manifestations of 7 cases
of Aarskog-Scott syndrome referred to
Kariminejad – Najmabadi Pathology & Genetics
Center, is shown in table 1.
rd
Genetics in the 3 millennium, Vol. 4, No. 4, Winter 2006
955
Aarskog-Scott syndrome
Among the patients referred to our genetic center
for psychomotor retardation, from 1995 to 2006,
seven cases were diagnosed with Aarskog-Scott
Syndrome. Round facies, hypertelelorism, downslanting palpebral fissures, small nose and broad
philtrum were constant features in all seven
patients. Ptosis was observed in 5 out of 7, and
4 out of 7 had maxillary hypoplasia, hypodontia,
short hand, clinodactyly of the fifth finger, pectus
excavatum and shawl scrotum. All cases were
male, consistent with X-linked inheritance of the
syndrome. Most cases (6 of 7) were referred
below the age of 7 years. Most of the patients
showed some degree of short stature, and all of
them had mild to moderate mental retardation.
956
rd
Genetics in the 3 millennium, Vol. 4, No. 4, Winter 2006
References
1. Aarskog D. A familial syndrome of short stature
associated with facial dysplasia and genital anomalies.
J Pediatr 1970; 77: 856
2. Scott CI. Unusual facies, joint hypermobility, genital
anomaly and short stature. A new dysmorphic syndrome.
Birth Defects Orig Artic ser. 1971; 7: 240-6
3. Jones KL. Smith's Recognizable patterns of Human
malformations. 6th ed. W.B. Saunders Company; 2006.
pp134-5
4. Goodman RM. The malformed infant and child; Oxford
University press; 1983. pp 208-9
5. Schwartz CE, Gillessen-Kaesbach G, May M, Cappa
M, Gorski J, Steindl K, et al. Two novel mutations confirm
FGD1 is responsible for the Aarskog syndrome. Eur J
Hum Gene 2000; 8: 869-74