++
A form of severe short-limbed dwarfism
with hair anomalies, defective immunity, and erythrogenesis.
++
Metaphyseal Chondrodysplasia McKusick type.
++
First recognized as a distinct entity in
the Old Order Amish, a religious group in the United States, in
1965 by the American geneticist V.A. McKusick, who is also the
founder and one of the editors of the “Online Mendelian
Inheritance in Man" (OMIM) database.
++
Clustering is found in Old Order Amish
(1-2 in 1000 live births) and in certain areas of Finland (1
in 23,000 live births). It is very rare in other populations.
No sexual predilection.
++
Autosomal recessive with
reduced penetrance. Caused by mutations of the mitochondrial
RNA-processing endoribonuclease gene, which is located on
9p21-p12. This enzyme is responsible for cleavage of RNA in the
mitochondrial DNA synthesis and for nucleolar cleaving of
pre-rRNA.
++
Defective cellular proliferation
has been described affecting predominately T-cells (resulting
in lymphopenia in almost two thirds of patients), but also
involves B-cells (low serum concentrations of immunoglobulins A
and/or G; in approximately one third of patients), neutrophils,
and fibroblasts. This syndrome has been suggested to result
from a generalized defect in cellular proliferation.
++
Incomplete extension in the elbows,
anterolateral chest deformity, genua varum, and excessive
distal length of the fibula relative to the tibia are specific
skeletal features. The major radiologic abnormalities are
confined to the metaphyseal regions of tubular bones. Biopsy
shows hypoplasia of cartilage to be the nature of the skeletal
abnormalities.
++
Radiographs show metaphyseal
dysostosis. The disorder may involve the cervical spine
(odontoid hypoplasia), the skeleton (short stature secondary to
dwarfism with an adult height usually <135 cm, flaring of the
lower rib cage at the costochondral junction, scoliosis, lumbar
hyper-lordosis, platyspondylia, narrowed interpeduncular
distances, small pelvic inlet, limited elbow extension,
metaphyseal dysplasia, fibular length exceeding tibial length
distally, short hands, brachydactyly, joint
hyperextensibility), the viscera (Hirschsprung disease,
esophageal atresia, anal stenosis, malabsorption), the teeth
(microdontia, anomalies of the incisors and premolars), and the
hair and skin (sparse, fine, light colored hair, redundant skin
folds around the neck and the extremities, hypopigmentation,
onychodysplasia). Laboratory investigations may show macrocytic
anemia, neutropenia, lymphopenia, and cellular
immunodeficiency. Recurrent pulmonary and opportunistic
infections in these patients are common (mainly Candida
albicans, Pneumocystis carinii, and Cytomegalovirus). Patients are predisposed to a severe course
of Varicella infection (multiple fatalities have been
reported) and malignancies (in approximately 5% of patients,
mainly non-Hodgkin lymphomas). Susceptibility to infections
usually improves in adulthood. The higher mortality in these
patients compared to the general population mainly refers to
children and is a result of the compromised immune system.
++
Obtain a complete
blood count with differentiation of red and white cells. The
degree of anemia may correspond to the degree of immune
deficiency. Anemia usually is mild, however, severe forms of
hypoplastic anemia of childhood have been reported. Assess the
airway for difficult intubation. Recurrent pulmonary infections
warrant careful evaluation of pulmonary function (chest
radiograph, arterial blood gas analysis, pulmonary function
test). Check cardiac function to delineate the extent of
cardiac compromise secondary to chest deformities and scoliosis
(electrocardiography, echocardiography). If any concerns exist
regarding the stability of the cervical spine, radiologic
examinations should be performed.
++
Strict aseptic technique
during insertion of lines, performance of any regional blocks,
and other invasive procedures is mandatory in the presence of
immune deficiency. Lumbar spinal or epidural anesthesia may be
difficult because of scoliosis, pronounced lumbar lordosis, and
diminished interpeduncular distance. Venous access often is
difficult because ...