What Is Chondrodysplasia Punctata?

Rhizomelic Chondrodysplasia Punctata Type 1 (RCDP type 1) is a group of diseases caused by different defective genes, including dominant or autosomal or sex chromosomes. Various types caused by genetic mutations in the recessive inheritance model. Among them, RCDP type 1 due to the abnormality of peroxisomal is an autosomal recessive genetic disease, and its clinical characterization is different from Another peroxisome abnormality; Zellweger syndrome. ^[1]

Proximal punctate cartilage dysplasia

Rhizomelic Chondrodysplasia Punctata Type 1 (RCDP type 1) is a group of diseases caused by different defective genes, including dominant or autosomal or sex chromosomes. Various types caused by genetic mutations in the recessive inheritance model. Among them, RCDP type 1 due to the abnormality of Peroxisomal is an autosomal recessive genetic disease, which is different from clinical characteristics Another peroxisome abnormality; Zellweger syndrome. ^[1]

Etiology of punctate cartilage dysplasia of the proximal limb

RCDP type 1 of abnormal peroxidation is characterized by patients with short stature, accompanied by spasticity and contractures, abnormal appearance, and severe mental retardation.

The patient's proximal limb (Rhizomelic), which is the upper arm humerus and lower thigh and femur, is significantly shorter, and often shows severe scoliosis and chronic lung infections, as well as cartilage with epiphyseal and dry ends. Bone (metaphyseal) abnormal point calcification (meaning chondrodysplasia punctata), bone x-ray imaging can be found after the bones (epiphyseal stippling). Plasmagens, which are low in blood, are an important basis for diagnosis.

Due to the poor prognosis, the average life expectancy of most patients is less than 10 years, and a significant proportion of deaths occur during the neonatal period.
Cases with milder symptoms are often manifested as congenital cataracts and cartilage dysplasia. Some patients do not have short limbs, while some patients have less severe growth and mental retardation.

Genetics of Proximal Pedal Cartilage Dysplasia

RCDP type 1 caused by the abnormality of the peroxisome in the genetic model is recessive inheritance of the somatic chromosome. If the parent is a carrier, it means that each chromosome has a defective gene. The gene on the other chromosome behaves normally, so it will not develop disease. But the next generation does not distinguish between men and women. Each child has a 25% chance of giving birth to this disease. A 50% chance is that they are the same carriers as their parents. A 25% chance is normal.

Diagnosis of punctate cartilage dysplasia of proximal limb

At present, the diagnosis of this disease mainly relies on genetic specialists to assess the clinical characteristics of patients and cooperate with relevant laboratory tests.
In biochemical tests, the function of peroxisomes can be assessed by examining the concentrations of plasmagens, phytanic acid, and VLCFA in the blood.
Refer to the following table for test values:

Ratio of C16 saturated dimethylacetals (DMA) to C16 saturated fatty acids
Normal value: 0.051-0.090	Outlier: 0.001-0.025
Ratio of C18 saturated plasmalogens to C18 saturated fatty acids
Normal value: 0.137-0.255	Outlier: 0.001-0.050
Phytanic Acid in the blood
Normal value: 0-2.5 g / mL	Outliers: typically up to 300 g / mL
Note 1: The above test values are applicable to typical patients. Those with mild symptoms may not be detected. Note 2: Phytanic acid usually comes from animal fats in the diet, so infants and young children may be normal on this test.

In addition, blood can be drawn through molecular biotechnology for genetic testing:

Detection method	Detection rate
Detection method	With two mutations	1 mutation
PEX7 gene sequence analysis	94%	6%

Clinical Characterization of Proximal Dystrophic Cartilage Dysplasia

Typical (Classic RCDP1):
Patients often show skeletal abnormalities, cataracts, stunted growth and mental retardation. The prognosis of this disease is poor. According to the treatment experience of Kennedy Krieger Research Center, 60% of patients survive 1 year, 39% are 2 years, and a few cases survive more than 10 years.

Clinical characterization	Representational description
Skeletal abnormalities	The bilaterally symmetrical proximal limbs (upper arm humerus and lower thigh femur) are significantly shorter, often resulting in muscle contracture, stiffness, and joint pain, causing discomfort and crying in infants. Facial cartilage is also often affected, causing forehead protrusions and short saddle noses.
cataract	Binocular cataracts occur in almost all patients, usually within one or the first few months of life, and gradually worsen.
Growth retardation	Height, weight, and head circumference usually fall into the lower normal range at birth, but then gradually slow down.
Mental retardation	Most infants have early developmental skills; such as smiling and recognizing sounds, but develop more slowly. The IQ is usually lower than 30, and the patient's developmental skills usually do not exceed the normal babies 6 months old.
other	Epilepsy is common in most children.
	Patients often suffer from repeated lung infections due to neurological lesions, foreign body inhalation, bedriding, and small thorax that limit lung expansion.
	Ichthyotic skin changes may occur in less than one-third of patients
	Jaw clefts can occur in 5-10% of patients.
	Possible congenital heart disease, ureteropelvic junction obstruction
Imaging findings	Conventional brain photography is normal or shows atrophy of the brain and cerebellum with enlarged ventricle and cerebrospinal fluid space. (Routine brain imaging is normal or has shown cerebral and cerebellar atrophy with enlargement of the ventricles and CSF spaces [Gilbert et al 1976, Wardinsky et al 1990, Powers et al 1999].) Brain magnetic resonance imaging revealed delayed myelin formation, abnormal signal conduction in the white matter on the sky, decreased choline synthesis of creatine, and an increase in the value of free lipids, which may be related to the decrease in plasmalogens that make up the myelin sheath. (MR imaging and MR spectroscopy have shown delayed myelinization, signal abnormalities in supratentorial white matter, decreased choline-to-creatine ratios, and increased levels of mobile lipids, thought to reflect the deficiency of plasmalogens, which are substantially components of myelin [Alkan et al 2003, Bams-Mengerink et al 2006].)

Light version (Mild RCDP1):
In the past, there have been reports of a small number of cases with mild clinical manifestations, including cartilage hypoplasia and cataracts. However, they are diverse in other features such as punctate calcification of the cartilage, short limbs, growth and retardation. For differences in clinical characteristics between cases, genetic testing of PEX7 can be used to assist clinical diagnosis.

Proximal punctate cartilage dysplasia treatment

Mainly for symptomatic treatment, ophthalmic surgery may reduce the problem of cataracts. In addition, it can be used for rehabilitation of limb problems, and regularly return to the department for follow-up to improve the quality of life and prognosis of patients.