Short-rib polydactyly

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Short-rib polydactyly

Definition

Short-rib polydactyly (SRP) syndromes are a group of skeletal dysplasias consisting of short ribs, short limbs, extra fingers or toes, and various internal organ abnormalities present at birth. There are four types of SRP and all are fatal shortly after birth due to underdevelopment of the lungs.

Description

In 1972, R. M. Saldino and C. D. Noonan first described two siblings with a dwarfism syndrome and symptoms of extremely shortened limbs, short ribs, small chest, abnormal bone formation, extra fingers, and internal organ damage. Since then, three additional SRP subtypes have been identified, all named after those who first described them. The subtypes are: SRP type I (Saldino-Noonan), SRP type II (Majewski), SRP type III (Verma-Namauf), and SRP type IV (Beemer-Langer). While each subtype has distinguishing features, there is a great amount of overlap between them. There is still debate about whether the different types are caused by different genetic changes or if they result from the same genetic change and are variable between patients. Some people believe that the subtypes are different expressions of a single syndrome.

The SRP syndromes also overlap with two other dwarfism syndromes, asphyxiating thoracic dysplasia (Jeune syndrome) and Ellis van Creveld syndrome. These syndromes, like the SRP types, have shortened limbs and ribs, small chest, and extra fingers or toes. These syndromes may all be genetically related.

The exact cause of these syndromes is unknown but they all result in abnormal bone development and growth prenatally. This causes shortened bones in the arms, legs, and ribcage. The ribcage is also constricting, leaving very little room for the lung growth. Development can also be abnormal in the internal organs, including the heart, kidneys, liver, and pancreas. The cause of death for these newborns is usually inability to breathe due to severely underdeveloped lungs.

Genetic profile

Even though the exact genetic cause of the SRP syndromes is unknown, it is well-documented that they are inherited as autosomal recessive conditions. This is because babies with SRP are born to unaffected parents and many parents have had more than one affected child. Parents of an affected child are assumed to be carriers. Those parents have a 25% chance of having another affected child with each pregnancy.

The gene (or genes) involved in the SRP syndromes has not yet been identified but is suspected to be on chromosome 4. Some researchers feel that the SRP gene is near the region of the gene for Ellis van Creveld syndrome on chromosome 4. The gene for another dwarfism syndrome, thanatophoric dysplasia , is also located in this area. Research is still being done to find the SRP gene (or genes) and learn more about its role during early development.

Demographics

Approximately 2-3 births per 10,000 are affected with some type of skeletal dysplasia. The SRP syndromes account for a small percentage of these. Due to the rarity of the SRP syndromes, an exact incidence is unknown.

Signs and symptoms

There is much overlap of symptoms between the SRP subtypes and it is often difficult to distinguish between them. They all have extremely shortened bones of the arms, legs, and ribs. They all also have a small, constricted chest.

Saldino-Noonan (type I) is considered the most severe type. Features reported with this type include spur formation on the bones, abnormal vertebrae (bones of the spinal column), and decreased ossification (hardening of the bones). Heart defects are common. Cysts are often seen on the kidneys and pancreas. Extra fingers and/or toes (polydactyly) are a classic feature and are usually on the same side of the hand/foot as the "pinkie" finger/little toe (postaxial). Sex reversal has also been reported. This means that the baby is genetically male but has visible female genitalia.

Majewski (type II) also has cystic kidneys and postaxial polydactyly. This type can also have preaxial polydactyly where the extra fingers/toes are on the same side of the hand/foot as the thumb/big toe. Other distinguishing features include cleft lip and palate and liver damage. The tibia (one of the bones of the lower leg) is often oval shaped and shorter than the fibula (the other bone of the lower leg). The ends of the bones may also appear smooth on an x ray.

Verma-Namauf (type III) has much overlap with Saldino-Noonan (type I) and may be a milder variant. Internal organ involvement is less common. The ends of the bones may appear jagged and widened on an x ray. The vertebrae are often small and flat. Polydactyly is also common in this type. Visible genitalia may be ambiguous (not clearly male or female).

Beemer-Langer (type IV), like Majewski, can have cleft lip and palate and liver damage. Cysts on the kidneys and pancreas are common. Polydactyly is usually absent but has been reported. A distinguishing feature of this type is bowed or curved bones.

Diagnosis

Diagnosis of the SRP syndromes can be difficult. A careful examination of internal organs and x ray evaluation is needed to distinguish SRP syndromes from Jeune syndrome and Ellis van Creveld syndrome. When SRP syndrome is suspected, x rays and internal organ involvement can also help to determine the particular type.

The main features of SRP syndromes (short bones, short ribs, small chest) can be seen on prenatal ultrasound. This is the only method of prenatal diagnosis for at-risk families. Genetic testing for the SRP syndromes is not available.

Treatment and management

There is no treatment or cure for the SRP syndromes. The abnormal prenatal bone development is irreversible. The chest is usually too small to allow for lung growth after birth. Internal organs with cysts may not be functional.

Infants born with SRP syndromes are given minimum care for warmth and comfort. Due to the poor prognosis, extreme measures to prolong life are rarely taken.