The Short-Rib Polysyndactyly Syndrome is a descriptive category for a group of lethal skeletal dysplasias caused by a ciliopathy and characterized by a hypoplastic thorax, short ribs, short limbs, polydactyly, and visceral abnormalities.
Polysyndactyly with Neonatal Chondrodystrophy; Saldino-Noonan Syndrome; Majewski Syndrome; Verma-Naumoff Syndrome; ☞Beemer-Langer Syndrome.
The Short-Rib Polysyndactyly Syndrome is subdivided into four types:
Type I: Saldino-Noonan Syndrome
Type II: Majewski Syndrome
Type III: Verma-Naumoff Syndrome
Type IV: ☞Beemer-Langer Syndrome (Short Rib Syndrome, Beemer type).
All variants are autosomal recessive.
The clinical features vary according to the type of the disease. They consist of:
Type I or Saldino-Noonan Syndrome: A lethal condition (dwarfism) in the newborn period. Mutation of the DYNC2H1 gene located on 11q22.3. The infant has a hydropic appearance, postaxial polydactyly, severely shortened and flipper-like limbs, and striking metaphyseal dysplasia of tubular bones. Severe micromelia is often noted. The cardiac system often presents a transposition of the great vessels. Ossification is defective in the calvaria and vertebrae. It also affects the pelvis and bones of the hand and feet. The pelvis resembles that in the Ellis-van Creveld Syndrome and the Asphyxiating Thoracic Dystrophy Syndrome. The visceral abnormalities involve gastrointestinal (GI) atresia, genitourinary atresia, and polycystic kidneys.
Type II or Majewski Syndrome: A lethal disease in the perinatal period. Mutation of the DYNC2H1 or NEK1 genes. It is characterized by the presence of median cleft-lip and palate, hypoplastic epiglottis, malformed larynx, and pulmonary hypoplasia. The presence of short ribs and gastrointestinal atresia may mislead the diagnosis and often it is suggested to be a Type I variant. However, the genitourinary system is largely affected with polycystic kidneys, ambiguous genitalia, and glomerular and renal tubular cysts. Neurologically, the presence of a hypoplastic cerebellar vermis and pachygyria is classical to this entity.
Type III or Verma-Naumoff Syndrome: Mutation of IFT80 or DYNC2H1 gene. The most important distinguishing features of this type are to be found in the skull: the cranial base is short, the forehead is bulging, the nasal bridge is depressed, and the occiput is flat. Another difference resides in the radiologic appearance of the long tubular bones, which show a distinct corticomedullary demarcation, somewhat widened metaphyses and marked longitudinal spurs. The neonatal period is often associated with asphyxiating episodes because of the narrow thorax and very short ribs. In comparison with Type II, the genitourinary system does not show as frequent abnormalities.
Type IV or Beemer-Langer Syndrome: Characterized by short ribs with pulmonary hypoplasia, associated with a variety of other visceral malformations. Short tubular bones, perinatal hydrops, and macrocephaly are present in virtually all children. Midline cleft with or without cleft palate, congenital heart disease, central nervous system malformations, GI and urogenital abnormalities are other frequently encountered features. The ...