A 10 days old female baby brought by parents with c/o-
abnormality of right upper limb since birth.
Antenatal :booked case;Inj.T.T;iron and folic acid
multivitamin supplementation taken.
No h/o diabetes,hypertension,thyroid disorders,fever
No h/o any drug intake.
Natal :term gestation,born though spontaneous
vaginal delivery,cried immediately after birth,birth
First born female child of non consanguionous
General examination:Baby warm,pink.
Respiratory:normal vesicular breath sounds.
CVS-s1s2 heard,no murmurs.
LOCAL EXAMINATION:right upper limb—flexed at
elbow and wrist.
Forearm pronated.ABSENT THUMB.
USG ABDOMEN-normal study.
2D Echo-osteum secundum type ASD.
X-RAY RIGHT UPPER LIMB-ABSENT RADIUS.
HOLT ORAM SYNDROME
Also called---Cardiac limb syndrome,cardiomelic
syndrome,atriodigital dysplasia,heart-upper limb
Genetically determined disorder in which aplasia or
hypoplasia of digital rays and/or radius associated with
congenital heart disease.
Holt and Oram first descibed this in 4 generation
family with atrial septal defects and thumb
CAUSES—Autosomal dominant and highly penetrant.
Initial linkage studies demonstrate gene defect on the
long arm of chromosome 12.
Molecular genetics revealed mutations that inactivate
the transcription factor TBX5,which is important in
the development of both upper limb and heart.
Sporadic disease represent a de novo germline
mutation in TBX5.
Frequency—0.95 cases per 1lakh total births.85% are due to
Sex—no sexual predilection.
Age– present at birth.
Subtle limb involvement may not become clinically
apparent until later in life when cardiac symptoms of
disease manifest or when an individual has a child with
more severe presentation of the syndrome.
Cardiac conduction disease is progressive with aging.
Middle aged individuals often present with AV block or AF.
ASD(ostium secundum and primum)
Coarctation of aorta,aortic arch malformations
Replaced subclavian artery.
Persistent left superior venacava.
Hypoplastic left heart.
Unilateral or bilateral and asymmetrical.
Absent thumb,triphalengeal thumb.
Pouse flotant(thumb connected by skin tag).
CARPAL BONE ANOMALIES.
Radial ray aplasia.
Aplasia of first metacarpals.
HOLT ORAM SYNDROME IS EXCLUDED IF ANY
FOLLOWING ANOMALIES PRESENT---
Vertebral(may or my not occur in HOLT ORAM)
PROGNOSIS—depends on severity of cardiac lesions.
Significant intracardiac shunts associated with sudden
death, pulmonary hypertension , Eisenmenger
The first clinical manifestation may be heart
failure,cardiac arrhyhmias(including heart block)or