Family history of patient
The patient (IV/20) was the 5th child of the family. At her birth time, her father was 33 and her mother 29 years old. The patient had four elder brothers between 15–18 years old. The eldest brother had a local seen dactyl (incomplete) between the 2nd and 3rd fingers of the foot.Her father (III/6) had a nephew (IV/3) born with a cardiac failure. Her major carotid artery was deformed and died after a cardiac surgery at 14 years old. Then, after 7 years, his brother's wife had an ectopic pregnancy with different abortions. She gave birth to a healthy daughter 10 years later. Even one of his brother's daughters (IV/10) had a mature death with unknown reason. Her family history did not show anything else ().
Patient's mother (III/29) had a cousin (III/17) who inherited a renal disease from his mother who was not a relative of patient's mother. There was a complete different cardiac disease (ASDI, mitral cleft) in one of the relatives (IV/22). One of her mother's uncle's daughters (II/22) died from a heart disorder associated with cyanosis very soon. Other members of relatives had no more problems. The relatives' relation was unknown. ()
Pregnancy, Birth and Infant Period
There was a pregnancy even with IUD which was exited later on. At the beginning of pregnancy, father has painted the house with a poisonous color (Xyladecor). Mother was infected with a dermal disease at the sixth month of pregnancy.
After calculating the term period and exiting green colored amniotic liquid, the patient had a quick birth. The patient had a length of 53 cm and weighted 3580 gr. There was not any measurement of her head round. After the birth, lack of thumb of the left hand and little growth of right hand's thumb were noticeable (–). On the 2nd
day of birth, unnatural heart voice was heard. On the 17th
day of birth, the patient was visited at a medical center. Then, it was specified that there were two shortages at atrium type II and a shortage at ventricle and lung artery.4
Little girl while writing showing the compatibility with right hand thumb difficulty.
A comparison of left and right hands after surgery.
The patient had a mental and physical growth in compliance with her age. At 6-months, she started to grasp her toys. But, due to the lack of power in her arms, she was treated with physiotherapy. When she was 13-months, she could walk. Even she had growth of teeth and speech with so much interest in cleanliness in compliance with her age and natural growth. She had a surgery on her left hand when was 15 months through which her thumb was replaced with a second finger. The mentioned surgery did not result in satisfaction of her mother and herself because it was difficult to grasp articles while in the past she could do the same task easily (). Professor Wilhelm performed the said surgery at Munich-Germany.
Furthermore, patient had a hyperplasia and dysplasia at her shoulder girdle and elbow joint ( and ). She could not raise her arms at shoulder joint more than 90° and /or turn her leg around her elbow joint (). Her shortage of ventricle was removed by a surgery when she was 9 years old. There were no more problems after that without any need to take any medicines. Regarding all signs and symptoms, she was diagnosed with atriodigital dysplasia. Therefore, in case of her marriage, we will have Tree No. 3 for her children situation. It means 50% of her children will have healthy genotype and phenotype and 50% of them will be heterozygote and carrier of the gene.
Defects in clavicle and shoulder girdle anomaly.
Defects in clavicle and shoulder girdle anomaly.
In this figure any difficulty in movement of shoulder joint andarm is completely obvious especially with bending fingers.
Holt-Oram Syndrome (atriodigital dysplasia syndrome)
This syndrome was defined for the first time in 1960.1
It includes a set of cardiac disorders and thumb aplasia and/or hypo-plaza which may arise in variety forms (different explanations) and with relative frequency of 1:100,000.3
Skeleton disorders may usually appear symmetrical and/or non-symmetrical in different cases. There are thin and bending shoulders with limited possibilities for turning of elbow joint which is probably related to hyperplasia of ulna in the length of thumb finger and secondarily, with radius in length of small finger, little growth of clavicle, anomaly of shoulder girdle, additional bones in wrist as other signs of this disease.2
Any mutation in TBX5, TBX3, TBX20SLL4 may cause pleiotropy related to HOS syndrome.8
The relevant signs of HOS in heart are shortage of atrium with arrhythmic and bracickardi, shortage in ventricle walls, and tetralogy of fallot.3
In some cases, they have thumb inflation towards its end. In 95% of family cases, any creation of cardiac shortage would be accompanied with some shortages in radius.20
Mostly, like the patient presented here, there are shortage in ventricle type II and/or shortage in atrium wall or mitral bend. Even any mistake in transfer of irritation may appear in a symbolic form (bracikardi, AU blockade, and practical defect of sinus groups).
There are some other results including Tabatznik syndrome, LEWIS and HARRIS-Osborn due to some similarities in different signs which should be recognized from atriodigital dysplasia. In Okihiro syndrome resulted from mutation in SLL4 gene on chromosome 20q13–13.2,12
the signs are similar to HSO but accompanied with an anomaly in eye muscles (lack of abducens nerve and disorders in eye movement). As a result, there will be a problem in site seeing towards left and right sides.1
Rather than tipped hand and cardiac problems, there are also some shortages in external ear with some hearing disorders and tipped rectum in Okihiro syndrome.1
There are some radius disorders with thrombocytopenia in T
bsent-Radius-Syndrome (TAR syndrome).17
In case of any complete hands hyperplasia, we should consider teratogenic cases.
According to the recent researches, it was obvious that about 30–35% of HOS cases are related to mutation of T-BX5 gene which is located on the long arm of chromosome 12 (12q24.1). There are 9 genes in this gene which include 2–9 coding proteins. T-BX5 protein is an effective factor in copying with 518 amino acids.4
On amino acid in neighboring an amino acid at the end of the amino acid is related to a deep track of DNA and any mutation in it is the real reason of cardiac disorders in HSO syndrome.5
Any change of amino acid at the carboxyl end may create a relationship with small DNA track and cause different shortages in upper organs.5
Microsatellites analysis in those families with diseased persons suffering from HOS may prove the place of other genes and also heterogenic situation of this disease. Different loci are considered such as 14q23, q24, 2 and 12q21-qtr. Different researches with MAPH (multiplex amplifiable probe hybridization) in those patients with lack of T-BX5 mutation shows a great omission in exons 3–9 of two related proteins of T-BOX.2
Human being genome has 7 genes (T-BX7-T-BX1) in T-BOX. The mutation of T-BX3 gene is the real reason of any autosomal shortage in radius.5
Up to now there are some reports about 15 reducing mutations of T-BX5 which are mainly of nonsense type and/or frame shift. For laboratory recognition purpose, it is enough to consider exons No. 7 of T-BX5 gene. But, it is recommended to study SLL4 gene as well.7