OMIM ID:
Asphyxiating Thoracic Dysplasia 1
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
This is a genetically and clinically heterogeneous condition for which the nosology remains to be worked out. Not all patients have ocular disease but those who survive infancy may have a pigmentary retinopathy resembling retinitis pigmentosa. In fact, a 5 year old presented with symptoms of visual loss and night blindness only. The severeity of the systemic malformations has so far precluded a full description of the ocular phenotype.
Systemic Features
The most life-threatening and characteristic systemic feature of ATD is short-ribbed thoracic constriction with respiratory insufficiency. The chest is small and narrow and sometimes described as bell-shaped. This deformity can lead to death by asphyxiation, and is a serious risk during infancy. Other individuals live to adulthood and may have only minimal respiratory difficulties. Patients who survive childhood can develop cystic renal and hepatic disease. Pancreatic fibrosis has also been reported. Brachydactyly and postaxial polydactyly are sometimes present and involve the feet more commonly than the hands. Short stature secondary to short limbs is frequently noted.
Genetics
Inheritance
Jeune syndrome, or at least some forms of it, is an autosomal recessive condition. Consanguinity is often present. A locus (15q13) containing homozygous mutations in ATD has been proposed as one candidate site. There is considerable genetic heterogeneity with at least 5 types described, all with mutations in different genes.
Another disorder with some similar features causing respiratory distress is Majewski syndrome (263520).
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.