AME case reports · 2026
Congenital hypothyroidism with preserved fifth digits in SMARCA4-related Coffin-Siris syndrome: a case report.
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Shah Swetang Jitendra, Ravi Usha, Dattani Aahna V, Mariswamy Arun Kumar Abhishek Kumar
Аннотация
BACKGROUND: Coffin-Siris syndrome (CSS) is an uncommon genetic condition that is generally associated with developmental delay, craniofacial dysmorphism, hypertrichosis, and hypoplasia or aplasia of the fifth digit. Genetic variations in genes that encode components of the SWI/SNF chromatin-remodeling complex, such as SMARCA4, are known to cause CSS with variable phenotype expression. The expanded use of genotype-first methods has contributed to the broadening of the awareness of non-classical presentations.
CASE DESCRIPTION: We present a case of a 10-year-old girl who presented for genetic evaluation because of developmental delay, anxiety with nonverbal behavioral predominance, cleft palate repair, microcephaly, and short stature. At the age of 3 months, she was diagnosed with congenital hypothyroidism and has been on constant levothyroxine. Examination physical examination showed hypertrichosis, mild craniofacial dysmorphism, and benign joint hypermobility, intact fifth digits and nails. A heterozygous variant in SMARCA4 was identified using trio exome sequencing (c.3315G>T) which revealed a de novo heterozygous variant. A variant of uncertain significance (VUS) in AP1S2 was also identified. Past cytogenetic and molecular testing had eliminated other genetic causes of syndromic developmental delay. The multidisciplinary management incorporated surgery revision of cleft palate repair, endocrine treatment, pharmacologic treatment of anxiety, behavioral treatment, and educational assistance.
CONCLUSIONS: The case presents a SMARCA4-associated phenotype of the CSS with intact fifth digits and with congenital hypothyroidism. This association has not been described in the literature to our knowledge. The findings reinforce the significance of genetic testing in children with complex patterns of development even without the traditional physical manifestations and propose that endocrine features can be considered further in SMARCA4-related CSS.
CASE DESCRIPTION: We present a case of a 10-year-old girl who presented for genetic evaluation because of developmental delay, anxiety with nonverbal behavioral predominance, cleft palate repair, microcephaly, and short stature. At the age of 3 months, she was diagnosed with congenital hypothyroidism and has been on constant levothyroxine. Examination physical examination showed hypertrichosis, mild craniofacial dysmorphism, and benign joint hypermobility, intact fifth digits and nails. A heterozygous variant in SMARCA4 was identified using trio exome sequencing (c.3315G>T) which revealed a de novo heterozygous variant. A variant of uncertain significance (VUS) in AP1S2 was also identified. Past cytogenetic and molecular testing had eliminated other genetic causes of syndromic developmental delay. The multidisciplinary management incorporated surgery revision of cleft palate repair, endocrine treatment, pharmacologic treatment of anxiety, behavioral treatment, and educational assistance.
CONCLUSIONS: The case presents a SMARCA4-associated phenotype of the CSS with intact fifth digits and with congenital hypothyroidism. This association has not been described in the literature to our knowledge. The findings reinforce the significance of genetic testing in children with complex patterns of development even without the traditional physical manifestations and propose that endocrine features can be considered further in SMARCA4-related CSS.