OMIM ID:
Majewski Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
No clinical information is available on the ocular features in this disorder. The fundi have been described as normal in one patient but postmortem histopathology at 8 weeks revealed optic nerve edema with segmental axonal dropout and loss of myelin. The nerve fiber layer of the retina was prominent with some proliferation of glial tissue. Early nuclear sclerosis was also present.
Systemic Features
This disorder results from a dysgenesis of the cilia and is one of a group of short rib-polydactyly disorders. Congenital anomalies are found in multiple organs including heart, lungs, skeleton, intestines, genitalia, pancreas, liver, and kidneys. The diagnostic characteristic of SRPS type II is extreme shortening of the tibia in addition to short ribs in this type of short-limbed dwarfism.
Midline facial clefting, especially cleft lip, is common. The epiglottis and lungs are often hypoplastic and the kidneys are polycystic. Polydactyly and polysyndactyly of both pre- and postaxial types are usually present. Most neonates with SRPS type II do not live beyond infancy.
Genetics
Inheritance
This is an autosomal recessive condition resulting from homozygous mutations in the NEK1 gene (4q33), or, rarely, from digenic biallelic mutations in NEK1 and DYNC2H1 (11q22.3).
Another condition with some of the same features leading to respiratory distress is asphyxiating thoracic dysplasia 1 (208500), or Jeune syndrome.
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.