A congenital syndrome with growth and mental
retardation, feeding difficulties, digital anomalies, and coarse facies.
Fifth Digit Syndrome; Dwarfism-Onychodysplasia Syndrome;
Short Stature-Onychodysplasia Syndrome.
First described by Grange S. Coffin, an American
pediatrician, and Evelyn Siris, an American radiologist, in 1970. To avoid
confusion with the Coffin Siris Wegienka Syndrome, it was decided to name
the latter syndrome Coffin-Lowry Syndrome (after Robert Brian Lowry, a
British medical geneticist, who described a fourth family with the findings
of Coffin-Siris-Wegienka Syndrome in 1971).
Since its first description, approximately 65 cases have
been reported. The male-to-female ratio is approximately 1:4.
The mode of inheritance is uncertain, but
is most likely autosomal dominant. However, a case
has been made suggesting autosomal recessive inheritance. It remains
possible that inheritance may not be mendelian in nature. The genetic defect
is thought to be in the 7q32-q34 region.
Based on the clinical findings of developmental delay,
mental retardation, hypoplasia of the fifth digit nail and terminal phalanges
of hands and feet, sparse scalp hair, bushy eyebrows, wide mouth, hirsutism,
and prominent or hypertrophied lips.
The constant finding is absence or hypoplasia of
the distal and middle phalanges, especially those of the fifth digits of the
hands and/or feet with aplasia/hypoplasia of the nail of the fifth digit
(other digits may also be affected). The other main features that have been
reported are low birth weight, failure to thrive (poor sucking and feeding
difficulties), and recurrent respiratory tract
infections. Central nervous system anomalies may include microcephaly,
generalized hypotonia, developmental delay, and mild-to-moderate mental
retardation, Dandy-Walker Malformation, hypoplasia/aplasia of the
corpus callosum, and abnormal and ectopic cerebellar nuclei. Sparse scalp
hair, long eyelashes, and bushy eyebrows contrast with hirsutism. In
addition, a wide mouth with prominent or thick lips, choanal atresia, flat
nasal bridge, anteverted and wide nasal tip, and high arched palate
(occasionally with cleft) are often present. Occasionally, ptosis, short
philtrum, and macroglossia occur. Short stature with vertebral anomalies
(kyphosis, scoliosis, spina bifida occulta, sacral dimple), joint laxity,
small patellae, and delayed bone age are fairly frequent. A variety of
associated cardiac defects have been described, including patent foramen
ovale, tetralogy of Fallot, atrial and ventricular septal defects, patent
ductus arteriosus, pulmonary stenosis, and persistent left superior vena
cava. Diaphragmatic hernia has been reported in a few patients. Urogenital
anomalies, such as hydronephrosis, congenital micro-ureters with stenosis at
the vesicoureteral junction, ectopic, small, or fused kidneys,
cryptorchidism, hypospadias, and uterus aplasia have been described. Ocular
anomalies are common and may include myopia, astigmatism, strabismus,
nystagmus, and tear duct anomalies. Mild-to-severe hearing loss is frequent.
Besides cardiac surgery, these patients often present for umbilical
and/or inguinal hernia repair. Recurrent infections (upper respiratory
tract, pneumonia, otitis media) are an ongoing issue in these patients. In a
subset of patients, recurrent hypoglycemic attacks, gastric outlet
obstruction, intestinal malrotation, and intussusception have been