A Collage of Hereditary Childhood Disorders
Published on Psychiatric Times
(http://www.psychiatrictimes.com)
A Collage of Hereditary Childhood Disorders
October 01, 2006
By Alexander K. C. Leung, MD [1], Alexander K. C. Leung, MD [1], and C. Pion Kao, MD [2]
his 7-year-old boy presented with mental retardation and delayed gross motor milestones: he first
sat up at 12 months, walked at 18 months, and ran at 2 years. His level of speech development was
that of a 5-year-old; his IQ was 75.
Fragile X Syndrome
This 7-year-old boy presented with mental retardation and delayed gross motor milestones: he first
sat up at 12 months, walked at 18 months, and ran at 2 years. His level of speech development was
that of a 5-year-old; his IQ was 75.
Physical examination revealed typical features of fragile X syndrome: large, prominent ears; a long,
narrow face; a high-arched palate; and a prominent jaw. Macroorchidism is usually not noted until
puberty. Physical and behavioral abnormalities are common; they include hyperactivity, short
attention span, poor eye contact, poor gross motor coordination, and echolalia.
Fragile X syndrome is inherited as an X-linked trait; it results from allelic expansion that begins as a
small increase in the copy number of trinucleotide repeats. The number of repeats may increase
from one generation to the next.
Earlier cytogenetic techniques for diagnosis used the presence of a fragile site on the X chromosome
at band q27.3 and depended on folic acid-deficient tissue culture medium. This test was not very
reliable; it detected almost half of obligate carriers. The diagnosis of fragile X syndrome is now made
by direct DNA analysis, which demonstrates an expanded segment of DNA from the q27.3 region.
Next to Down syndrome, fragile X syndrome is the most common cause of mental retardation that
can be specifically diagnosed. Horner Syndrome
This 5-year-old girl had drooping of the left upper eyelid and a small left pupil at birth. At around 1
year, a blue iris was noted in the left eye and a brown iris in the right eye. She also had a decrease in
facial sweating and occasional flushing on the left side of the face.
Miosis, ptosis, apparent enophthalmos (with or without anhidrosis), flushing on the side of the lesion,
and heterochromia iridis are typical features of Horner syndrome, which results from an obstruction
of sympathetic outflow from the hypothalamus to the orbit. The condition may be inherited as an
autosomal dominant trait. An acquired form may result from birth trauma, thoracic surgery,
neuroblastoma, ganglioneuroma, and congenital Cytomegalovirus infection.
The sympathetic nervous system is intimately associated with the development of normal eye color.
If paralysis of the ocular sympathetic fibers occurs before age 2, hypopigmentation of the iris on the
affected side may result. Since pigmentation of the iris is completed by about age 2, injury to the
sympathetic nervous system after this time does not result in heterochromia.Prader-Willi
Syndrome
Morbid obesity and developmental delay were the presenting features of this 8-year-old boy. He was
the product of an uncomplicated pregnancy and a full-term normal, spontaneous delivery. His weight
at birth was 6 lb 2 oz. Decreased fetal movements were noted in the third trimester of the
pregnancy. In the neonatal period, he was observed to have a weak cry, hypotonia, micropenis,
hypoplastic scrotum, and undescended testicles. Gross motor milestones of sitting, crawling,
walking, and running were delayed, as was speech development.
Bilateral orchidopexy was performed when the boy was 2; he became a voracious eater at about this
time. He had microdontia and numerous dental caries that required a number of dental restorations
and extractions.
Physical examination revealed that the boy weighed 100 lb (15 lb above the 95th percentile) and
was 126 cm tall (50th percentile). He had a relatively narrow forehead, with low-set and slightly
rotated ears. His hands and feet were both very small and he had down-slanting palpebral fissures.
He also had a small penis, hypoplastic scrotum, and rudimentary testicles. His IQ was 70.
This patient has Prader-Willi syndrome, which is characterized by hypotonia, hypomentality,
hypogonadism, and obesity (H3O syndrome). Other manifestations include microdontia, enamel
hypoplasia, high-arched palate, small hands and feet, scoliosis, compulsive snacking, and
compulsive skin-picking.
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A Collage of Hereditary Childhood Disorders
Published on Psychiatric Times
(http://www.psychiatrictimes.com)
More than 50% of patients with Prader-Willi syndrome have anomalies of chromosome 15, notably a
deletion of the proximal part of the long arm (del 15q11 - q13), and at times, an unbalanced
translocation in that region. Less frequently, a 15;15 translocation or isodicentric chromosome 15 is
found.
Potential complications in patients with Prader-Willi syndrome include dental caries, diabetes
mellitus, hypertension, atherosclerosis, joint contracture, osteoporosis, glomerulosclerosis, and
development of a pickwickian or obesity-hypoventilation syndrome.Down Syndrome
This 3-month-old girl has typical features of Down syndrome: upward-slanting palpebral fissures;
protruding tongue; flat nasal bridge; flat occiput; short neck with redundant skinfolds; Brushfield
spots; short, broad hands and fingers; clinodactyly of the fifth fingers; simian creases; wide spaces
between first and second toes; and hypotonia.
Most persons with Down syndrome (trisomy 21) have an extra chromosome 21. In 95% of cases, this
results from meiotic nondisjunction--a condition that increases with advancing maternal age: nearly
half of affected persons are born to women older than 35 years. Approximately 1% of affected
persons are mosaic, with a mixture of normal and trisomic cells. The remaining 4% have a
translocation involving chromosome 21.
Children with Down syndrome have varying degrees of mental retardation; their IQs usually range
from 20 to 80. Approximately 45% have congenital heart disease, notably endocardial cushion
defect. A higher than normal incidence of other disorders is seen in children with Down syndrome.
These include atlantoaxial instability, duodenal atresia, Hirschsprung disease, imperforate anus,
Hashimoto thyroiditis, and acute leukemia. Ehlers-Danlos Syndrome
This 2-year-old girl had hyperelastic skin (A), very elastic and pliable ears (B), and hyperextensible
joints. Her mother and grandmother had similar clinical features; the mother's hyperextensible joints
are seen in photograph C.
The child has Ehlers-Danlos syndrome, an inherited connective tissue disorder. At least 11 types of
this genetically heterogeneous condition have been described. The essential defect is a quantitative
deficiency of collagen.
Children with Ehlers-Danlos syndrome are prone to poor wound healing with "cigarette paper" scars;
easy bruisability; Raynaud phenomenon; inguinal, umbilical, incisional, and hiatal hernia; diverticula
and perforation of the GI tract; joint effusion and recurrent dislocation; kyphoscoliosis; joint
contracture; mitral valve prolapse; and dissecting aneurysm.
Source URL: http://www.psychiatrictimes.com/articles/collage-hereditary-childhood-disorders
Links:
[1] http://www.psychiatrictimes.com/authors/alexander-k-c-leung-md
[2] http://www.psychiatrictimes.com/authors/c-pion-kao-md-0
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