Autosomal recessive infantile malignant osteopetrosis
generic name that represents a group of heritable conditions in which there is
a defect in osteoclastic bone resorption. Patients with osteopetrosis display
macrocephaly, progressive deafness and blindness, hepatosplenomegaly, and
severe anemia beginning in early infancy or in fetal life. Deafness and
blindness are generally thought to represent effects of pressure on nerves.
Autosomal dominant osteopetrosis shows mild symptoms while autosomal recessive
infantile malignant osteopetrosis is a more severe form. 5 forms of autosomal
recessive infantile malignant osteopetrosis have been described: OPTB1
caused by the mutation in the TCIRG1 subunit of the vacuolar proton
pump, OPTB4 (
which is caused by mutation in the CLCN7 gene, OPTB5 (
which is caused by mutation in the OSTM1 gene, a milder, osteoclast-poor form
is caused by mutation in the TNFSF11 gene, an intermediate form OPTB6
is caused by mutation in the PLEKHM1 gene, and a severe osteoclast-poor form
OPTB7 associated with hypogammaglobulinemia (
is caused by
mutation in the TNFRSF11A gene and
a form of autosomal recessive osteopetrosis associated with renal tubular
acidosis, OPTB3 (
is caused by mutation in the gene encoding carbonic anhydrase II. The incidence
of autosomal recessive osteopetrosis is estimated to be 1:200000.
is the most frequent form of short-limb dwarfism. It is characterised by short
stature caused by rhizomelic shortening of the limbs, characteristic facies
with frontal bossing and midface hypoplasia, exaggerated lumbar lordosis,
limitation of elbow extension, genu varum, and trident hand. Achondroplasia is
an autosomal dominant disorder. The gene for achondroplasia is fibroblast
growth factor receptor-3 gene (FGFR3) located in the distal area of the short
arm of chromosome 4 (4p16.3). Occurrence of this disease is about 1 in 26,000
(it affects all races and both genders).
Carbonic Anhydrase Deficiency (
anhydrase coded by
Carbonic anhydrases genes (CAs) are a large family of zinc metalloenzymes that
catalyze the reversible hydration of carbon dioxide requied for cellular
respiration, calcification, acid-base balance, bone resorption, and the
formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. CAs
are encoded by members of 3 independent CA gene families, i.e., alpha-CA,
beta-CA, and gamma-CA.
Erythrocyte carbonic anhydrase has 2 isoenzymes CA I (or A) and CA II (or B).
Most common form of Carbonic anhydrase deficiency is Carbonic anhydrase II (CA
II) deficiency (
an extremely rare autosomal recessive disorder, characterised by a triad of
osteopetrosis, renal tubular acidosis and cerebral calcifications.
The database presently holds the relevant data for CA II.
Papillon-Lefevre syndrome (
disease is characterized by periodontitis and palmoplantar keratoderma, leading
to early loss of both milk-teeth and permanent teeth, and associated
hyperkeratosis of palms and soles of feet appearing in first few years of life.
Papillon-Lefevre syndrome is caused by mutations in the cathepsin C gene
(CTSC), the disorder being inherited in an autosomal recessive manner. The
syndrome affects 1 to 4 persons per million.
Haim Munk Syndrome (
syndrome (HMS), an autosomal recessive disorder, can be caused by mutations in
the gene encoding cathepsin C. I fact, Haim-Munk Syndrome and Papillon-Lefevre
syndrome are caused by allelic variants of the same gene. This is a rare
syndrome of congenital palmoplantar keratosis, pes planus, onychogryphosis,
periodontitis, arachnodactyly, and acroosteolysis (to some degree similar to
the Papillon-Lefevre syndrome).
Dyskeratosis congenita (
disease mainly affects the integumentary system with a major
consequence being anomalies of the bone marrow. The disorder is
characterised by premature aging with cutaneous pigmentation, dystrophy of the
nails, leukoplakia of the oral mucosa, continuous lacrimation due to atresia of
the lacrimal ducts, often thrombocytopenia, anemia, and in most cases
testicular atrophy. Only males are affected in a pattern consistent with
X-linked recessive inheritance as a result of one or more mutations in the long
arm of the X chromosome in the gene DKC1.
may result in specific issues related to dysfunctional rRNA and perhaps a
Rhizomelic Chondrodysplasia Punctata type 1
(also known as "Autosomal recessive chondrodysplasia punctata type 1”), is a
rare, multisystem developmental disorder characterized by dwarfism due to
systemic shortening of the proximal bones (i.e. rhizomelia), specific
radiologic abnormalities, joint contractures, congential cataracts, ichthyosis,
and severe mental retardation. It is caused by mutations in the PEX7 gene,
which encodes the peroxisomal type 2 targeting signal (PTS2) receptor.
MIM: 223800 )
(DMC) Disease is a part of a subgroup of osteochondroplasias known as
spondylo-epi-metaphyseal dysplasias (SEMDs) characterized by malformations of
the vertebra, with abnormal ossification of long bone epiphyses and metaphyses.
DMC, an autosomal recessive disorder, is a progressive SEMD with additional
clinical features that include short trunk dwarfism, microcephaly, facial
dysmorphism, and variable mental retardation. The disease is caused by
mutations in the Dymecilin (DMC) gene.
X-linked hypophosphatemic rickets (
MIM: 307800 )
X-linked hypophosphatemic rickets,
although variable in its expressivity, is characterized by rickets with
bone deformities, short stature and dental anomalies. Hypophosphatemia with low
renal phosphate reabsorption, normal serum calcium level with hypocalciuria,
normal or low serum level of vitamin D (1,25(OH)2D3, or calcitriol), normal
serum level of PTH, and increased activity of serum alkaline phosphatases are
also noticeable. Mutations in the PHEX gene cause this disease. The prevalence
of the disease is 1:20000.
Hereditary Hypophosphatemic Ricket with Hypercalciuria (
MIM: 241530 )
hypophosphatemic rickets is a disorder related to low levels of phosphate in
the blood, the signs and symptoms beginning in early childhood. The features of
the disorder vary widely, even among affected members of the same family. They
develop bone abnormalities that can interfere with movement and cause bone
pain, most noticeable being bowed legs or knock knees. The disease is caused by
defects in SLC34A3 gene and is transmitted in an autosomal recessive mode.
Familial tumoral calcinosis (
MIM: 211900 )
Familial tumoral calcinosis
is a rare autosomal recessive metabolic disorder characterized by
hyperphosphatemia and progressive deposition of basic calcium phosphate
crystals in periarticular spaces, soft tissues, and sometimes bone. Most
cases are caused by mutation in the GALNT3 gene.