Pediatric Holt-Oram Syndrome Clinical Presentation

Updated: Aug 05, 2015
  • Author: Poothirikovil Venugopalan, MBBS, MD, FRCPCH; Chief Editor: Syamasundar Rao Patnana, MD  more...
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Presentation

History

Clinical features of Holt-Oram syndrome (HOS) vary depending on the severity of the cardiac and limb malformation. [12, 13] Note the following:

  • Individuals with more severe congenital heart defects may present in the neonatal period. Abnormalities may also be detected in utero using fetal ultrasonography and fetal echocardiography.

  • Cardiac symptoms depend on the type of congenital heart defect. Atrial septal defect (ASD), the most common heart defect in HOS, causes no symptoms in the vast majority of affected individuals.

  • Severity of cardiac and limb malformations appears to be positively correlated in some studies; however, this has not been replicated in other studies.

  • In any sporadic case of ASD, the patient and parents should be examined for limb malformations, and the family history should be studied in detail.

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Physical

Physical findings may include musculoskeletal and/or cardiac defects. Intelligence in patients with Holt-Oram syndrome (HOS) is normal.

Musculoskeletal defects

Note the following:

  • Upper limbs are usually affected, although the importance of isolated lower limb involvement associated with specific mutations has been reported. [14]

  • Although bilateral, the left side is often more significantly affected.

  • The most severe form is phocomelia with rudimentary limbs.

  • Mildest forms include clinodactyly, limited supination, and sloping shoulders.

  • The most common defects include radial thumb anomalies ranging from absent thumbs to displaced (distally placed), duplicated, or triphalangeal thumbs. Carpal and metacarpal anomalies (especially the fourth) may also be present. Refer to the following images.

    Photograph of the left hand of a 6-month-old infan Photograph of the left hand of a 6-month-old infant with Holt-Oram syndrome showing total aplasia of the left thumb.
    Photograph showing hypoplastic right thumb of the Photograph showing hypoplastic right thumb of the right hand of a 6-month-old infant with Holt-Oram syndrome.
  • Hypoplasia of the radius manifests as short deformed forearm, although it may be so mild that it is detectable only on radiography of the forearm (see image below)

    Plain radiograph of the right forearm and hand of Plain radiograph of the right forearm and hand of a 5-month-old infant with Holt-Oram syndrome showing hypoplastic radius and ulna and only 4 metacarpals.
  • Sprengel deformity (upward displacement of the scapula) and hypoplasia of the shoulders, clavicles, and humerus have also been reported.

  • The number and location of hypoplastic muscles correlate with the severity of skeletal involvement. Accordingly, patients with hypoplasia of large and proximal muscles have phocomelia, and those with intrinsic hand muscle hypoplasia have only a triphalangeal thumb or no skeletal malformation.

  • Associated muscular hypoplasia that involves the hypothenar, wrist extensor, supinator, biceps brachii, triceps brachii, deltoid, pectoral, and trapezium muscles has also been reported.

  • Isolated (sporadic) patients have more severe involvement, which can include the ulnar ray.

Heart defects

Note the following:

  • The reported incidence ranges from 50-95%.

  • The most common lesion is a secundum astrial septal defect (ASD). Others include ventricular septal defect (VSD), atrioventricular (AV) block, pulmonic stenosis (including peripheral arterial), and mitral valve prolapse.

  • Approximately 17% of patients have more complex cardiac malformations, such as tetralogy of Fallot, hypoplastic left heart syndrome, endocardial cushion defects, and truncus arteriosus. Cardiac arrhythmias include paroxysmal atrial tachycardia, prolonged PR interval, wandering atrial pacemaker, atrial ectopics, AV block, and sinus bradycardia. Syncope and sinus arrest have been reported. Multiple VSDs have also been reported.

  • According to Mglinets, "a specific feature of the syndrome is a change in the main palmar lines and their termination on the radial border of the hand not only in the absence of the thumb but also in the case of formation of the abortive xT-line, its radiants, and the axial triradius." [15]

  • Pulmonary hypoplasia has occasionally been reported and can present with neonatal respiratory distress. [16, 17] No other associated visceral anomaly has been reported.

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Severity Scoring System

A scoring system to assess severity of Holt-Oram syndrome (HOS) anomalies has been recommended by Gall et al and modified by Gladstone and Sybert. These are outlined below.

Skeletal defects

A scoring system to assess skeletal abnormalities in HOS is as follows:

  • 0 - No abnormality on physical or radiological examination

  • 1 - Minor abnormalities, including reduced thenar eminence, clinodactyly, or hypoplasia of the thumb

  • 3 - Present arms and forearms, with one or more bones missing

  • 4 – Phocomelia

Cardiac defects

A scoring system to assess cardiac abnormalities in HOS is as follows:

  • 0 - Asymptomatic, with no abnormal physical findings

  • 1 - Conduction defect

  • 2 - Structural heart abnormality that does not require surgery

  • 3 - Structural heart abnormality that requires surgery but is not life threatening

  • 4 - Potentially lethal malformation

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