CWH C1361296

 A

Based on the combination of IUGR, cleft palate, VSD, hypospadias, and choroid plexus cysts, while specifically considering that the CGH array (microarray) is normal, the differential diagnosis shifts toward single-gene disorders (Mendelian conditions) rather than large chromosomal deletions or duplications.

Here are three primary syndromic differentials for this presentation:

1. Smith-Lemli-Opitz Syndrome (SLOS)

SLOS is an autosomal recessive disorder of cholesterol biosynthesis (DHCR7 gene). It is a "classic" differential for this specific constellation because it mimics chromosomal abnormalities but will return a normal microarray.

• Key Findings: IUGR, cleft palate, cardiac defects (like VSD), and notably underdeveloped male genitalia (hypospadias/ambiguous genitalia).

• Unique Sign: Postaxial polydactyly or 2-3 toe syndactyly (webbing) is very common.

• Diagnostic Tip: Diagnosis is made via a serum 7-dehydrocholesterol (7-DHC) level or gene sequencing, not CGH.

2. Opitz G/BBB Syndrome

This syndrome primarily affects midline structures and can be inherited in X-linked (MID1) or autosomal dominant forms.

• Key Findings: Hypospadias is a hallmark of this condition. It also frequently includes cleft lip/palate and congenital heart defects (VSD/ASD).

• Clinical Clues: Look for hypertelorism (widely spaced eyes) and laryngeal/esophageal anomalies (breathing or swallowing issues).

• Note: Because it is often a single-gene mutation, a standard CGH array will usually be normal unless it is part of a larger 22q11.2 microdeletion (which would have been caught on the array).

3. Kabuki Syndrome

Kabuki syndrome is a multiple congenital anomaly syndrome (KMT2D or KDM6A genes) that can present with a very broad phenotype prenatally.

• Key Findings: It is associated with IUGR, cleft palate, and VSD in roughly 30–50% of cases. Genitourinary anomalies like hypospadias or cryptorchidism are also reported.

• Clinical Clues: Postnatally, it is identified by "persistent fetal finger pads" and characteristic facial features (long palpebral fissures with eversion of the lower eyelid).

• Array Status: Standard CGH is almost always normal; diagnosis requires Exome Sequencing (WES).

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Summary Table

Feature	Smith-Lemli-Opitz	Opitz G/BBB	Kabuki Syndrome
Growth	Severe IUGR	Variable	Postnatal/Late IUGR
Genitalia	Hypospadias/Ambiguous	Hypospadias	Hypospadias (less common)
Cardiac	VSD/ASD/AVSD	VSD/ASD	VSD/Coarctation
Next Step	7-DHC level / DHCR7 gene	MID1 or 22q11.2 testing	KMT2D/KDM6A sequencing