A 10 days old female baby brought by parents with c/o-abnormality of right upper limb since birth.

BIRTH HISTORY:Antenatal :booked case;Inj.T.T;iron and folic

acid multivitamin supplementation taken.No h/o diabetes,hypertension,thyroid

disorders,fever with rash.No h/o any drug intake.Natal :term gestation,born though

spontaneous vaginal delivery,cried immediately after birth,birth weight-2.5 kg.

First born female child of non consanguionous marriage

General examination:Baby warm,pink.Cry,tone-normal. No pallor,icterus,cyanosis,clubbing.Heart rate-122/min;R.R-42/min;CFT<3sec.SYSTEMIC EXAMINATION:Respiratory:normal vesicular breath sounds.CVS-s1s2 heard,no murmurs.P/A-soft.LOCAL EXAMINATION:right upper limb—

flexed at elbow and wrist.Forearm pronated.ABSENT THUMB.

INVESTIGATIONS-CBP-Hb-14.2gm%,TWBC-7400cells/cc(N-

62%,L-34%,E-1,M-2,B-0);Platelets-2.2lakh/cUSG ABDOMEN-normal study.2D Echo-osteum secundum type ASD.X-RAY RIGHT UPPER LIMB-ABSENT

RADIUS. .

X ray right upper limb

HOLT ORAM SYNDROMEAlso called---Cardiac limb

syndrome,cardiomelic syndrome,atriodigital dysplasia,heart-upper limb syndrome.

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 abnormalities.

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.

EPIDEMIOLOGYFrequency—0.95 cases per 1lakh total births.85%

are due to new mutations.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.

CARDIAC MANIFESTATIONS

ASD(ostium secundum and primum)VSD. CONDUCTION DEFECTS.MS,MVP,PDA,TOF,PS, TGA.Coarctation of aorta,aortic arch

malformationsReplaced subclavian artery.Persistent left superior venacava.Hypoplastic left heart.

SKELETAL DEFORMITIESUnilateral or bilateral and asymmetrical.Absent thumb,triphalengeal thumb.Pouse flotant(thumb connected by skin tag).clinodactily.,syndactily.CARPAL BONE ANOMALIES.Radial ray aplasia.Aplasia of first metacarpals.Phocomelia.Shoulder defects.

HOLT ORAM SYNDROME IS EXCLUDED IF ANY FOLLOWING ANOMALIES PRESENT---

Ulnar boneLower limbsKidneys,eyesauditory,CraniofacialVertebral(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 syndrome.

The first clinical manifestation may be heart failure,cardiac arrhyhmias(including heart block)or infective endocarditis.

Differential diagnosis:VACTERLTRISOMY 18 ( EDWARD)THALIDOMIDE EMBRYOPATHYFanconi ‘s anemiaTAR syndrome

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