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American Journal of Medical Genetics 80:396–398 (1998)
Brief Clinical Report
Association of Terminal Chromosome 1 Deletion
With Sertoli Cell-Only Syndrome
Eba H. Hathout,1* Kevin Thompson,1 Marti Baum,1 and Kenneth W. Dumars2
Division of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California
Genzyme Genetics, Orange, California
We report on del(1)(q44), developmental delay, cryptorchidism, and seizure disorder in
a 19-year-old man. Endocrinologic evaluation showed delayed puberty and elevated
gonadotropins. Testicular biopsy was consistent with Sertoli cell-only syndrome. The
case illustrates a previously an unreported
manifestation in males with del(1)(q44), and
suggests a link between the development of
germinal epithelium and genes in the 1q44
area. Am. J. Med. Genet. 80:396–398, 1998.
© 1998 Wiley-Liss, Inc.
KEY WORDS: del(1)(q44); Sertoli-cell only
syndrome; delayed puberty
Terminal deletion of the long arm of chromosome 1 is
associated with a characteristic combination of neurologic, developmental, and genital abnormalities [Arai
et al., 1984; Johnson et al., 1985; Meinecke and Vogtel,
1987; Murayama et al., 1991; Watson et al., 1986].
Little has been reported regarding underlying hormonal or histologic gonadal pathology. We report on a
male with del(1)(q44) in whom hypergonadotropism
and testicular biopsy were consistent with the Sertoli
cell-only syndrome [Del Castillo et al., 1947; Heath,
1973]. To our knowledge, this is the first report of such
an association.
The propositus was the first child of a healthy 28year-old mother and a nonconsanguineous 28-year-old
Dr. Dumars is Professor Emeritus of Pediatrics at the University of California, Irvine, as well as consultant geneticist at Genzyme Genetics, Inc.
*Correspondence to: Eba H. Hathout, M.D., Division of Pediatric Endocrinology, Loma Linda University School of Medicine,
11370 Anderson Street, Suite B-100, Loma Linda, CA 92354.
Received 27 April 1998; Accepted 6 August 1998
© 1998 Wiley-Liss, Inc.
father. He had one cousin with Down syndrome. Family history was otherwise unremarkable. The patient
was delivered vaginally at term following an uncomplicated pregnancy. Birth length, weight, and head circumference (OFC) were <5th centile. He had retrognathia, large low-set ears, a short neck, calcaneovalgus, micropenis, and hypospadias. Lips and palate
were intact. Seizures were noted in early infancy. Multifocal abnormalities were identified on electroencephalogram, and computed tomography scan of the brain
showed absent corpus callosum. Severe mental retardation necessitated institutionalization.
At 19 years the patient was referred for endocrine
evaluation to rule out hypothyroidism as a cause of
constipation (Fig. 1). Examination showed a small-forage male with a short nose; epicanthal folds; round
face; retrognathia; thin upper lip; large low-set ears
with left anterior ear tags; short neck; and severe flexion contractures of the wrists, elbows, hips, and knees.
Genital exam showed Tanner stage IV pubic hair, a
small right testicle (Tanner stage II), and a well-healed
scar (following removal of the undescended left testicle). The penis was uncircumcised and of normal
length and appearance (hypospadias was surgically
corrected in infancy).
A hand radiograph showed delayed bone age (艋2
SD), and marked osteopenia. Screening for growth,
thyroid, and cortisol hormones was normal. Plasma
level of follicle stimulating hormone (FSH) was elevated at 24.9 mU/mL (reference 0.9–15), luteinizing
hormone (LH) was elevated at 11.3 mU/mL (reference
4.6–9.4), and testosterone was 29,097 pmol/L (838 ng/
dL; reference 194-833 ng/dL). LH and FSH responses
to intravenous gonadotropin releasing hormone
(GnRH) were exaggerated (peaks of 46 and 50 mU/mL,
Peripheral leukocytes were cultured and harvested
and the chromosomes were GTG banded using routine
methods. A 46,XY,del(1)(q44) was found (Fig. 2). Fluorescence in situ hybridization studies with a 1q441qter probe (D1S555, Oncor) and a chromosome 1 centromeric probe (D1Z5, Oncor) as a control showed that
one chromosome 1 long arm is deleted at the 1q44-qter
Del (1q) and Sertoli Cell-Only Syndrome
Fig. 2. Top: Idiogram of chromosome 1 illustrating the anomaly (arrow
indicating the normal monosomic region). Bottom: Six G-banded partial
karyotypes of the patient are shown, with the normal chromosome 1 on the
left of each pair, and the homolog with del 1q on the right of each pair.
[Juberg et al., 1981]. It is noteworthy that the above
manifestations do not differ significantly in relation to
the level of the deletion (i.e., 42-qter vs. 44-qter). Despite recognition of genital anomalies in this syndrome,
little attention has been paid to underlying histologic
or endocrine pathology.
The Sertoli cell-only syndrome, also known as germinal aplasia, is a rare disorder present in about 30% of
azoospermic males. It was first described by Del Castillo et al. in 1947. Characteristics include normal virilization, small testes, and a testicular biopsy showing
small seminiferous tubules without germinal epithelium, lined only by Sertoli cells. Chromosome analysis
was mostly normal in reported cases apart from a few
Klinefelter mosaic or Down syndrome cases [Averback,
1980; DeKrester et al., 1972; Guay et al., 1977]. FSH
levels are elevated in both urine and blood, testosterone levels are low or normal, and FSH and/or LH responses to GnRH are frequently exaggerated [Guay et
al., 1977].
It is clear from the above discussion that our patient
has most of the manifestations of terminal 1q, and the
hitherto undescribed association with Sertoli cell-only
syndrome. Advances in molecular genetics may elucidate the above association in previously studied pa-
Terminal deletion of the long arm of chromosome 1 is
associated with a characteristic combination of craniofacial, neurologic, and genital anomalies [Arai et al.,
1994; Johnson et al., 1985; Loan et al., 1992; Manouvrier-Hanu et al., 1986; Meinecke and Vogtel, 1987;
Murayama et al., 1991; Watson et al., 1986]. While
most terminal del(1q) cases were de novo, some were
due to an inherited inversion or translocation [Golabi
et al., 1982; Juberg et al., 1981; Speevak et al., 1985].
Findings in terminal del(1q) syndrome include growth
and mental retardation; corpus callosum hypoplasia;
speech delay; microcephaly; up-slanting palpebral fissures; epicanthal folds; short broad nose; low-set abnormal ears; down-curved mouth; micrognathia; short
neck; heart defects; abnormal feet; general hypotonia;
and seizures. Genital anomalies are described more
frequently in males and range from genital hypoplasia,
hypospadias, or shawl scrotum to intersex genitalia
Fig. 3. Testicular biopsy: seminiferous tubules showing only Sertoli
cells without the presence of germinal epithelium. The Leydig cell population in the interstitia appears unremarkable (×100).
Fig. 1. Propositus at age 19 years.
region in all metaphase figures examined. Parental
chromosomes were normal.
Retrospective histologic review of testicular tissue
(Fig. 3) showed slightly narrowed tubules lined by a
layer of elongated Sertoli cells without presence of germinal epithelium, consistent with the Sertoli cell-only
Hathout et al.
tients with germinal aplasia, whose karyotypes were
‘‘normal.’’ This is particularly of value for genetic counseling purposes. The association also adds to the list of
chromosome abnormalities in males with delayed puberty and/or infertility. The relevance in females remains to be studied. The above finding suggests a link
between the development of germinal epithelium and
genes in the 1q44 area. However, more patients need to
be studied to asses the validity of the above association.
Arai E, Nishimura S, Tamura K, Kida M, Ikeuchi T (1994): Chromosome 1q
terminal deletion resulting from de novo translocation with an acrocentric chromosome. Jpn J Human Genet 39:433–437.
Averback P (1980): Branching of seminiferous tubules associated with hypofertility and chronic respiratory infection. Arch Pathol Lab Med 104:
DeKrester DM, Burger HG, Fortune D, et al (1972): Hormonal, histological, and chromosomal studies in adult males with testicular disorders.
J Clin Endorinol Metab 35:392–401.
Del Castillo EB, Trabucco A, de la Balze FA (1947): Syndrome produced by
absence of the germinal epithelium without impairment of the Sertoli
or Leydig cells. J Clin Endocrinol Metab 7:493–502.
Golabi M, Ito M, Hadley D (1982): Double neural tube defects in two sib-
lings; new features of chromosome 1 deletion syndrome 1q43. Am J
Hum Genet 34:125A.
Guay AT, Tuthill RJ, Woolf PD (1977): Germinal cell aplasia: Response of
luteinizing hormone (LH), follicle stimulating hormone (FSH), and testosterone to LH/FSH-releasing hormone with histopathologic correlation. Fertil Steril 28:642–649.
Johnson VP, Heck LJ, Carter GA, Flom JO (1985): Deletion of the distal
long arm of chromosome 1: A definable syndrome. Am J Med Genet
Juberg RC, Haney NR, Stallard R (1981): New deletion syndrome: 1q43.
Am J Hum Genet 33:455–463.
Loan DM, Maximillian C, Kleczkowska A, Fryns JP (1992): Distal deletion
of the long arm of chromosome number 1(q43–qter) associated with
severe mental retardation and a nonspecific dysmorphic syndrome.
Ann Genet 35:167–169.
Manouvrier-Hanu S, Walbaum R, Gayot C (1986): A new case of distal
deletion of the long arm of chromosome 1. [letter to the editor] Am J
Med Genet 25:599–600.
Meinecke P, Vogtel D (1987): A specific syndrome due to deletion of the
distal long arm of chromosome 1. Am J Med Genet 28:371–376.
Murayama K, Greenwood RS, Rao KW, Aylsworth AS (1991): Neurological
aspects of del(1q) syndrome. Am J Med Genet 40:488–492.
Speevak M, Hunter AGW, Hughes H, Cox DM (1985): A familial paracentric inv(1)(q42q44) resulting in a child with a del(1)(q42) karyotype.
Ann Genet 28:177–180.
Watson MS, Gargus JJ, Blakemore KJ, Katz SN, Breg WR (1986): Chromosome deletion 1q42-43. Am J Med Genet 24:1–6.
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