8/26 w/cryptorchidism /or micropenis Hypothyroidism

6/46

—

Immunodeficiency

31/46

—

Neurologic abnormalities

22/46

Cranial nerve deficits (11/46); Strabismus (6/46); Ptosis (2/46); Developmental delay (9/46); Regression/progressive neurologic involvement (6/46); Peripheral motor sensory neuropathy (5/46)

Spasticity Sensorineural hearing loss

8/45

—

Ichthyosis/acanthosis

13/46

1. , , The range of renal involvement extends from nonimmune fetal hydrops at the severe end to delayed evidence of nephrosis for many years after diagnosis or no renal involvement after years of follow up, as observed in two sibs in their twenties and thirties .

LAMB2

Pierson syndrome (OMIM 609049)

AR

Steroid-resistant nephrotic syndrome; developmental delay

Lysosomal acid lipase deficiency

AR

Adrenal calcifications

Hepatic fibrosis cirrhosis; intestinal malabsorption LMX1B

Nail-patella syndrome

AD

Steroid-resistant nephrotic syndrome; sensorineural hearing loss

Nail dysplasia; hypoplastic or absent patellae; eye anomalies NPHS1 NPHS2

PLCE1

Congenital nephrotic syndrome types 1, 2, 3 (OMIM 256300, 600995, 610725)

AR

Steroid-resistant nephrotic syndrome

Schimke immunoosseous dysplasia

AR

Steroid-resistant nephrotic syndrome; T-cell lymphopenia

Spondyloepiphyseal dysplasia; numerous lentigines AD = autosomal dominant; AR = autosomal recessive; DiffDx = differential diagnosis; MOI = mode of inheritance; SPLIS = sphingosine phosphate lyase insufficiency syndrome 1. Table 4.

Differential Diagnosis of Clinical Findings Associated with Sphingosine Phosphate Lyase Insufficiency Syndrome Clinical Finding

Distinguishing Features

Comment

—

Motor/sensory neuropathy

Often autosomal dominant

See Charcot-Marie-Tooth Hereditary Neuropathy Overview.

—

Congenital ichthyosis

Acanthosis may be observed in SPLIS.

Congenital ichthyosis is a feature of several genetic syndromes.; Nonsyndromic ichthyosis (e.g., autosomal recessive congenital ichthyosis) can be considered if ichthyosis is the presenting finding; syndromic ichthyosis can be assoc w/Netherton syndrome, Sjgren-Larsson syndrome, trichothiodystrophy

—

Nonimmune hydrops

Enlarged/hemorrhagic adrenals

Many genetic conditions are assoc w/fetal hydrops (e.g., chromosome anomalies, RASopathies, lysosomal storage disorders).1 Primary adrenal insufficiency

Adrenal calcifications, hypothyroidism, cryptorchidism, micropenis may be assoc w/primary adrenal insufficiency.

Musculoskeletal

Orthopedics/ physical medicine rehab/ PT OT eval

To incl assessment of:; Gross motor fine motor skills; Contractures kyphoscoliosis; Mobility, ADL, need for adaptive devices; Need for PT (to improve gross motor skills) /or OT (to improve fine motor skills)

Hearing

Audiologic eval

For sensorineural hearing loss

Speech

Speech language pathology assessment

For those w/DD /or hearing loss

Development

Developmental assessment

To incl:; Motor, adaptive, cognitive, speech-language eval; Eval for early intervention/ special education Ichthyosis/

Acanthosis

Dermatology referral if skin abnormalities

Genetic

counseling

By genetics professionals1

To inform affected persons their families re nature, MOI, implications of SPLIS to facilitate medical personal decision making Family support resources

Treatment of Manifestations in Individuals with Sphingosine Phosphate Lyase Insufficiency Syndrome Manifestation/Concern

Treatment

Considerations/Other Steroid-resistant nephrotic syndrome

Primary adrenal insufficiency

By pediatric endocrinologist

Glucocorticoid replacement; Mineralocorticoid replacement as required ± sodium supplementation; Appropriate counseling for sick days; emergency perioperative mgmt Hypothyroidism

Immunodeficiency

Care by immunologist

Monitor absolute lymphocyte count over time. If proliferation is abnormal, consider avoiding live vaccines. Most affected persons have normal or near-normal T-cell function despite absolute levels. To consider: supportive therapy (e.g., IVIG) to prevent infection based on history lab testing.

Failure to thrive

Search for underlying etiology, e.g., renal or endocrine problem.

Consider input from nutritionist, parenteral feeding.

DD/ID

See .

Neurologic

involvement

Seizure management

Rule out electrolyte disturbances hypoglycemia.; Information is insufficient re specific antiseizure mgmt.