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The Coffin-Lowry syndrome

Article in European Journal of Pediatrics · January 1984

DOI: 10.1007/BF00445790

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 European Journal of

Eur J Pediatr (1984)143:82-86 Pediatrmcs

9 Springer-Verlag 1984

Original investigations
The Coffin-Lowry syndrome
A study of two new index patients and their families

M. Haspeslagh 1., J. P. Fryns 1, L. Beusen 2, F. Van Dessei 2, L. Vinken3, E. Moens 4, and H. Van De n Berghe 1
1Division of Human Genetics, Department of Human Biology, A. Z. Gasthuisberg, Onderwijs en Navorsing, Herestraat 49, 3000-
Leuven, Belgium
2Instituut Borgerstein, IJzerenveld 147, 2500 St. Katelijne-Waver,
Belgium 3Sint-Oda Instituut, Breugelweg 200, 3583 Overpelt, Belgium
4 Algemeen Kinderziekenhuis Antwerpen, Albert Grisarstraat 13, 2018 Antwerpen, Belgium

Abstract. Two adult, mentally retarded males with the typical a heterogeneous group of different entities. Afte r the dis-covery
features of the Coffin-Lowry syndrome are reported . Furthe r family [7] and the confirmation of the fragile X syndrome [11], medical
investigation led to the same diagnosis in a 2.5-year-old male cousin, interest in this subject has increased during the past few years.
and to the identification of five female carriers, with variable clinical Within t.his group of disorders the Coffin-Lowry syndrome
expression of this X-linked inherited mental retardation syndrome. constitutes a rare, clinically recognisable entity, with partial
expression of the clinical stigmata in female carriers [4].
Key words: Coffin-Lowry syndrome - X - linked mental retard -
ation - Dysplasia syndrome
Report on the families

Introduction Family 1
X-linked mental retardation, which is responsible for the excess of S . J . , a male ( I I I b Figs. 1-4), was the eldest in a family of four
males among the mentally retarded [13] constitutes children, two boys and two girls. His psychomotor develop-

Pedigree Family I Pedigree Family II

deceased

N
male wlth Coffin - Lowry S.

rv
n o texamined
0 f e m a l e c a r r i e r with
@ f a c i a ldysmorphy
f e m a l e carrier w i t h

tapering fingers
female carrier with slight
manta 1 r e t a r d a t i o nand / o r
psychotic behavlour
k y p h o s e o l i o s i s w i t h v e r t e b r a ld y s p l a s i a
Fig.1. Pedigree of families I and
II * Corresponding author

Fig.2, Facial appearance of patient III1, family I (age 35 years)
Fig.4. Radiograph of thoracolumbar spine of patient III1 with
verte-bral dysplasia
83
ment was retarded from the beginning and he only started to walk
at 24 months. As a child he was admitted to a special institute for
the mentally retarded and examined during a systematic study of
the mentally retarded.
A t his present age of 35 years his length is 152 cm, his weight
70 kg and his head circumference 56 cm. His face is
characteristically coarse with heavy bowed eyebrows, hyper-
telorism and down-slanting of the somewhat narrowed palpe-bral
fissures. Other facial anomalies included large ears, a big nose
with a broad and flattened nasal tip and a large open mouth with
full everted lips (Fig. 2). Skeletal deformities were severe with
thoracolumbar kyphosis, pectus carinatum and caleaneovalgus
deformity of the feet. His hands were large and soft (Fig. 3) with
tapered fingers and a hypothenar crease. Radiographic
examination of the hands showed hypoplastic, drum-stick type
terminal phalanges (Fig.3); in the spine dys-plasia of the
thoracolumbar vertebrae was seen (Fig. 4).
The mother (II~), aged 58 years, has a round face with pro-
minent brows, a broad nasal bridge with thick septum and full,
everted lips. Her hands show typical tapering of the fingers and a
transverse crease on the hypothenar eminence. Her
Fig.3. Radiograph of the band of
patient IIIl, showing hypo-plastic
tufted termi-nal phalanges
mental state is difficult to evaluate due to a cerebrovascular
accident some years ago, but family members describe her as
mentally retarded. She had three healthy brothers (II~,z,3) and one
sister (14). He r sister has been hospitalised in a psychiatric
hospital since the age of 20 years due to psychotic behaviour and
slight mental retardation. He r face shows prominent brows and a
very lax skin with "peau de p6che" appearance. Her hands and
fingers are normal.
The eldest sister (Ilia) could not be examined but photo-graphs
reveal small stature and coarse facial features like her mother,
with typical tapering fingers. She is slightly mentally retarded,
and has three children, two boys and one daughter. The youngest
son (IV3) was born after a normal pregnancy and delivery. The
birth weight was 2900 g, the length 49.5 cm. A t the age of 2
months surgical correction of an inguinal hernia was performed.
Soon after birth severe developmental delay was noted. A t 2
years his length and weight were below
84
Fig.5 Fig.6
Fig.7 Fig.8
Fig. 7. Facial appearance of patient IIi, family II (age 28 years)
Fig. 8. Large soft hands, with tapering fingers of patient II~, family II. Note accessory hypothenar crease
Fig. 9. Facial appearance of mother (I2) of patient II1 of family II
the third centile and bone age was severely retarded ( l year). Now
at the age of 2.5 years he cannot walk without support. Clinical
examination showed a typical coarse face with anti-mongoloid
slanting of the palpebral fissures, upturned nose and large mouth
with protruding lips (Fig. 5). The hands were broad with tapered
fingers (Fig. 6). His joints were lax with generalised axial and
peripheral hypotony. Mild pectus ex-cavatum was present but
there was no scoliosis. Tomography of the brain showed large
ventricles.
The eldest son and the daughter were mentally normal. The
youngest sister (IIL) resembles her mother closely
(IIs). She presents the same facial stigmata and her hands are large
and soft without distinct tapering. Radiographic exami-nation
showed tufted terminal phalanges. He r mental state is normal.
Family H
C.C. (II1, Figs. 1,7,8) was the first born in a family with two boys.
The pregnancy was uneventful and the birth weight was 3100 g.
His developmental milestones were retarded and at
Fig.5. Facial appearance of patient
IV3 of family I, at the age of 2 years.
Patient presents results of a burn
Fig. 6. Hands with tapering fingers
of patient IV3 of family I
Fig.9
the age of 7 he was admitted to an institute for the moderately and
severely mentally retarded. A t the age of 28 years he was severely
mentally retarded and s h o w e d a peculiar waddling gait. His
measurements were: length 137 cm, weight 42 kg and head
circumference 53 cm. His face is coarse with prominent
supraorbital ridges, heavy arched eyebrows, ptosis of eyelids,
hypertelorism and anti-mong01oid slanting of palpebral fis-sures.
The nose ls large with broad nasal slope and alae nasi. The ears
were large (7-51/2 cm) a n d everted. The mouth is large, open and
bowTshaped with prominent tips, protruding tongue and only three
remaining teeth. His back shows a severe thoracolumbar
kyphoscoliosis with pectus carinatum, calcaneovalgus deformity
of the feet, hyper-extensibility of joints and large soft hands with
tapered fingers. There is an extra hypothenar crease (Fig. 8).
Radiographs of the hands showed tufted, shortened drum-stick
type terminal phalanges, at the thoracolumbar spine severe
vertebral dysplasia was seen.
Familial data were scanty and difficult to obtain. His mot-her
(Ia, Fig. 9) shows a round face with somewhat prominent supra-
orbital ridges, a big nose with broad septum and full
 85

Table 1. Clinical findings in female patients with Coffin-Lowry syndrome

Coffin et al. Lowry et al. Procopis Tentamy et al. Fryns et al. Hunter et al. Koussef Present
(1966) [2] (1971) [6] and Turner (1975) [12] (1977) [3] (1982) [4] (1982) [51 paper
(1972) [10] ++ ++
+
Mental status
Severe M.R.
-t- ++ + +
Slight to moderate M . R . +++ ++ ++ ++
M.R. level unknown ++ + + + +
Normal intelligence ++ +
++ + ++++ + +++ + ++ ++ ++++
Face
Typical features
Normal/discrete + + + ++ + + +
+ + + + + + +++++ ++-+-
+ + + ++++ -+++
Hands
Tapering
Hypothenar crease + - + +-- + +
+ + + - - + +++-
+ +; +
Reduced stature
+ Present
- Not present
M.R. mental retardation

everted lips. Her hands are large and soft with tapered fingers.
She is slightly mentally retarded .
Discussion
Afte r the original publication of Coffin et al. [2] more than 15
reports have dealt with this mental retardation syndrome, in which
all males thus far reporte d are severely mentally retar-ded and
present with a clinical picture characterised by typical facial, hand
and skeletal malformations.
In adult males the facial features are diagnostic. The most
salient features are: a broad quadrangular forehead with pro -
minent supra - orbital ridges and heavy arched eyebrows,
hypertelorism with anti - mongoloid slanting of the palpebral
fissures and ptosis of the eyelids, a big nose with thick septum, a
large open mouth with protruding tongue, irregular or miss-ing
teeth, big everted lips and large everted ears.
The large soft hands with thick lax skin and puffy tapering
fingers are probable diagnostic since they are never found in other
mental retardation syndromes. Dermatoglyphic studies
consistently show a transverse hypothenar crease [9].
The most frequent and salient skeletal changes are thick-ened
calvaria, spinal kyphosis and scoliosis, with dysplasia of the
vertebral bodies at the thoracolumbar junction, hypoplas-tic drum-
stick type terminal phalanges and retarded bone age. Other less
constant changes include pectus carinatum or ex-cavatum and
cervical ribs [4], narrow iliac wings and shorten-ing of the long
bones of the lower limbs [12].
The clinical findings in our (family I, patient 1113) and other
patients recognised early [14] indicate that the diagnosis in
infancy is much more difficult. The face is less dysmorphic, the
coarseness only appears after aging. A t birth these chil-dren are
hypotonic with hyperlaxity of joints. The early onset of internal
hydrocephaly, as found in our patient, is probably responsible for
the major neurological symptoms in these children. Soon after
birth they present with a severe develop-mental delay and retarded
In contrast to the male patients, the clinical expression in
females is variable, sometimes overlapping with a nearly nor-mal
phenotype . Fro m our patients and the literature we col-lected 29
well - documented females with the Coffin-Lowry syndrome.
These findings are summarised in Table 1.
Besides, the reduced mental fitness (21/29) and the varia-ble
facial changes, tapere d fingers (24/27) and reduced stature (17/24
< 160 cm) are the most constant findings in female patients.
According to present knowledge it seems evident that some of the
obligate female carriers are mentally normal and do not present
evident facial or limb abnormalities.
With regard to the genetics, this familial mental retarda - tion
syndrome is transmited in a vertical pedigree pattern. Few
sporadic cases have been described [4, 8, 12, 14]. They may only
be accepted after careful clinical and radiological examination of
female relatives. As supported by most authors [3, 10] the finding
of mildly abnormal or nearly nor-mal females and always severely
affected males suggests X-lin-ked inheritance. The presence in
many families of abortions or early deaths mainly of male patients
[6, 10, 12] may indicate X-linked semi - dominant inheritance with
lethality in severely affected males. However, because of the
absence of male-to-male transmission, autosomal dominant
inheritance with more severe expression in males cannot be fully
excluded.
The coarse facies, loose joints, lax skin and the skeletal
changes suggest a connective tissue disorder [4, 12]. Our two
index patients, although during aging their faces coarsened, have
not revealed signs of degeneration or further mental deterioration
during the last 10 years. This observation pleads against the
progressive, degenerative nature of this disease and supports a
structural defect with deliterous effects on growth and
development . Recently Beck et al. [1] found abnormalities in
proteodermatan - sulphate metabolism in patients with this mental
retardation syndrome.
References

bone age. Tapere d fingers are pre-sent at birth and seem to be the 1. Beck M, G16ssl J, Rfiter R, Kresse H (1983) Abnormal
most reliable feature in infancy. proteo-dermatan sulfate in three patients with Coffin-Lowry
syndrome. Pediatr Res 17 : 926-929
86
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Received January 30, 1984 / Accepted June 22, 1984
 BY THE HISTORICALmethod alone can many problems in medicine be approach-
ed profitably.

Sir William Osler

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