CWH C1361296

 A

PERUX MACHU PICHU

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